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A number sign (#) is used with this entry because of evidence that Cole disease (COLED) is caused by heterozygous mutation in the ENPP1 gene (173335) on chromosome 6q23. Description Cole disease is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013). Clinical Features Cole (1976) reported a family in which 6 members over 3 generations had a diffuse variegated pattern of hypopigmentation affecting almost the entire body; all affected members also had punctate keratosis of the palms and soles. The proband was an 18-year-old man who developed a diffuse irregular macular speckled pattern of hypopigmentation at 6 months of age, which remained unchanged and asymptomatic thereafter. Keratotic papules on his palms and soles were first noted at 3 years of age and also remained asymptomatic. Examination revealed moderately dark pigmented normal skin with sharply demarcated irregular macules showing varying degrees of hypopigmentation scattered diffusely over most of the body, with relative sparing of the acral portions of the body, including the head, neck, nipples, elbows, knees, genitalia, hands, and feet; there was no correspondence to a vascular or dermatomal pattern. The hypopigmented areas ranged in size from 1 to 15 mm in diameter, and many of the macules had small 1- to 2-mm islands of darker pigmentation within them. In addition, numerous flat-topped hypopigmented keratotic papules were present on the palms, soles, and dorsolateral aspects of the fingers and toes, varying from 2 to 6 mm in diameter; the papules did not seem to be concentrated over areas of trauma. Mucous membranes, irides, hair, teeth, and nails were all normal. The proband reported that his mother, maternal grandfather, and 3 brothers were similarly affected, although none of the family members were available for examination. Skin biopsy of hypopigmented skin showed focal areas of mild elongation of the rete ridges, with abundant melanin granules in the basal cell layer and other layers of the epidermis, and occasional small collections of melanophages in the upper dermis. The proband's normal skin showed a slight increase in melanin pigment in the basal cell layer, but was otherwise histologically similar to the hypopigmented skin. Biopsy of a palmar papule showed hyperkeratosis overlying a cup-shaped depression in the epidermis. Mild hypergranulosis and acanthosis was present, with an occasional melanocyte in the basal cell layer. Moore et al. (2009) described a 2-year-old boy with congenital guttate hypopigmentation on the extremities as well as asymptomatic papules on the soles that first appeared at 3 months of age. There was no family history of similar skin lesions. Examination revealed irregularly shaped 2- to 10-mm hypopigmented macules on the extremities and scattered 2- to 8-mm pinkish-yellow keratotic papules on the soles. Hair, teeth, and nails were normal. Biopsy of hypopigmented skin showed patchy hypomelanosis and normal melanocyte density with rare melanophages in the papillary dermis. Biopsy of the largest plantar papule showed orthokeratosis and acanthosis, with small deposits of calcium in the papillary dermis. Eytan et al. (2013) reviewed the clinical data for affected members of 2 multiplex French families who had hypopigmented macules primarily over the extremities and hyperkeratotic papules of the palms and soles. In addition to skin manifestations, 2 affected individuals from the first family exhibited early-onset calcific tendinopathy of the shoulders, wrists, hips, and heels, and 1 of the patients also had microcalcifications on mammography and a large splenic calcification. In the second family, 1 of the patients demonstrated calcinosis cutis. Serum phosphate and fasting glucose levels were normal in the patients tested. Inheritance The inheritance pattern of Cole disease in 2 French families studied by Eytan et al. (2013) was autosomal dominant. Molecular Genetics In 2 French families with hypopigmented macules primarily over the extremities and hyperkeratotic papules of the palms and soles, as well as the similarly affected family previously described by Moore et al. (2009), Eytan et al. (2013) performed whole-exome capture and next-generation sequencing and identified 3 different heterozygous missense mutations in the ENPP1 gene (173335.0020-173335.0022) that segregated with disease in each family, respectively. All 3 mutations involved highly conserved cysteine residues in the somatomedin-B-like-2 (SMB2) domain of ENPP1. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Normal teeth CHEST Breasts \- Microcalcifications on mammography (in some patients) ABDOMEN Spleen \- Splenic calcification (in some patients) SKELETAL Pelvis \- Calcific tendinopathy of hips (in some patients) Limbs \- Calcific tendinopathy of shoulders (in some patients) \- Calcific tendinopathy of wrists (in some patients) Feet \- Calcific tendinopathy of heels (in some patients) SKIN, NAILS, & HAIR Skin \- Hypopigmented macules, primarily on extremities \- Punctate palmoplantar keratoderma Skin Histology \- Hyperkeratosis \- Hyperorthokeratosis \- Hypergranulosis \- Acanthosis \- Reduction in melanin content in keratinocytes \- Normal melanin content in melanocytes \- Normal number of melanocytes \- Small deposits of calcium in papillary dermis (in some patients) Electron Microscopy \- Increased melanosomes in cytoplasm and dendrites of melanocytes \- Paucity of melanosomes in keratinocytes Nails \- Normal nails Hair \- Normal hair MUSCLE, SOFT TISSUES \- Calcific tendinopathy, early-onset (in some patients) MISCELLANEOUS \- Skin lesions manifest in the first year of life \- Hair, teeth, and nails are normal MOLECULAR BASIS \- Caused by mutation in the ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1, 173335.0020 ) ▲ 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	COLE DISEASE	c3809781	30,000	omim	https://www.omim.org/entry/615522	2019-09-22T15:51:51	{"omim": ["615522"], "orphanet": ["324561"], "synonyms": ["Guttate hypopigmentation and punctate palmoplantar keratoderma", "Alternative titles", "Cole disease", "GUTTATE HYPOPIGMENTATION AND PUNCTATE PALMOPLANTAR KERATODERMA WITH OR WITHOUT ECTOPIC CALCIFICATION", "Hypopigmentation and punctate keratosis of the palms and soles"]}
A number sign (#) is used with this entry because autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O) is caused by heterozygous mutation in the DYNC1H1 gene (600112) on chromosome 14q32. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). Clinical Features Weedon et al. (2011) reported a large 4-generation family with autosomal dominant inheritance of an axonal peripheral neuropathy consistent with CMT. Affected individuals presented in childhood with delayed motor milestones and/or an abnormal gait and difficulty running. Physical examination showed slowly progressive distal lower limb weakness and wasting with pes cavus deformity. Upper limb involvement was less common, and ambulation was usually maintained through adulthood. Nerve conduction studies were within the normal range, and sural nerve biopsies demonstrated changes consistent with axonal degeneration. Some individuals had transient paresthesia and neuropathic lower limb pain. There was significant variability in some other features: reflexes could be lost or preserved, and the degree and modality of distal sensory impairment also varied. Some had learning difficulties. Inheritance The transmission pattern of CMT2O in the family reported by Weedon et al. (2011) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a large 4-generation family with autosomal dominant axonal CMT2O, Weedon et al. (2011) identified a heterozygous mutation in the DYNC1H1 gene (H306R; 600112.0001). The mutation was identified by exome sequencing. Weedon et al. (2011) noted that mouse models had implicated mutations in this gene in neuropathic disease (Hafezparast et al., 2003). INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy NEUROLOGIC Central Nervous System \- Delayed motor development \- Learning difficulties (less common) Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Upper limb involvement may occur \- Recurrent falls \- Neuropathic pain \- Difficulty running \- Distal sensory impairment, variable \- Hyporeflexia \- Normal or mildly decreased motor nerve conduction velocity (NCV) \- Sural nerve biopsy shows axonal degenerative process MISCELLANEOUS \- Onset in childhood \- Slowly progressive \- Variable phenotype \- One family has been reported (as of September 2011) \- Ambulation is usually maintained during adulthood MOLECULAR BASIS \- Caused by mutation in the dynein, cytoplasmic 1, heavy chain 1 gene (DYNC1H1, 600112.0001 ) ▲ 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	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2O	c3280220	30,001	omim	https://www.omim.org/entry/614228	2019-09-22T15:55:59	{"doid": ["0110175"], "omim": ["614228"], "orphanet": ["284232"], "synonyms": ["Alternative titles", "CMT2O", "CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2O", "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2O"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Ulnar deviation" – news · newspapers · books · scholar · JSTOR (May 2017) (Learn how and when to remove this template message) For ulnar deviation as a type of hand movement, see Ulnar deviation under Anatomical terms of location. Hand affected by Ulnar deviation Ulnar deviation, also known as ulnar drift, is a hand deformity in which the swelling of the metacarpophalangeal joints (the big knuckles at the base of the fingers) causes the fingers to become displaced, tending towards the little finger. Its name comes from the displacement toward the ulna (as opposed to radial deviation, in which fingers are displaced toward the radius). Ulnar deviation is likely to be a characteristic of rheumatoid arthritis, more than of osteoarthritis. Consideration should also be given to pigmented villonodular synovitis, in the setting of ulnar deviation and metacarpophalangeal synovitis. Ulnar deviation is also a physiological movement of the wrist, where the hand including the fingers move towards the ulna. Ulnar deviation is a disorder in which flexion by ulnar nerve innervated muscles is intact while flexion on the median nerve side is not. This medical symptom article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ulnar deviation	c0449752	30,002	wikipedia	https://en.wikipedia.org/wiki/Ulnar_deviation	2021-01-18T18:51:06	{"umls": ["C0449752"], "wikidata": ["Q2475429"]}
Chronic primary adrenal insufficiency (CPAI) is a chronic disorder of the adrenal cortex resulting in the inadequate production of glucocorticoid and mineralocorticoid hormones. ## Epidemiology It is a rare disease with a prevalence of about 1/ 7, 100 and an annual incidence of about 1/ 250, 000 in Western populations. ## Clinical description Disease onset peaks around 40 but can occur at any age. It presents insidiously with nonspecific symptoms that can be mistaken for other more prevalent conditions. Common manifestations include fatigue, loss of energy, malaise, weight loss, nausea, anorexia (failure to thrive in children), muscle and joint pain. Pigmentation of skin and mucous membranes (darkening of the skin especially in the palmar creases, knuckles, scars, oral mucosa and sites of friction) is a cardinal sign of CPAI. Symptoms of postural hypotension and hypoglycemia are late manifestations. Patients may also crave salt. Vitiligo (see this term) and alopecia areata are often present when an autoimmune disorder is the cause. CPAI also causes dehydroepiandrosterone deficiency causing additional symptoms seen only in women (loss of axillary/pubic hair, absence of pubarch in children, reduced libido and dry skin). Acute adrenal insufficiency (AAI; see this term) can occur if treatment is not followed or during precipitating illnesses and is a life threatening medical emergency. ## Etiology The most common cause of CPAI in the developed world is Addison disease (AD; see this term), also known as autoimmune adrenalitis , seen in 80%-90% of cases. Autoimmune adrenalitis can be isolated or seen as part of an autoimmune disorder (autoimmune polyendocrine syndrome type 1, 2 or 4; see these terms). Infiltrative disorders are another cause of CPAI and include tuberculosis (see this term), fungal infections and AIDS-associated opportunistic infections. Genetic disorders (i.e. congenital adrenal hyperplasia; see this term), tumors, and treatment with certain drugs are other less common causes. ## Diagnostic methods Biochemical tests are needed to diagnose CPAI. Early morning serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels are measured. Plasma ACTH is much higher in individuals with CPAI (>22 pmol/L) and morning serum cortisol levels are usually low (<83nmol/L) but can fluctuate. A stimulation test observing the cortisol response to exogenous ACTH is a useful tool in confirming a diagnosis. In healthy subjects serum cortisol concentrations increase (>500 nmol/L) after exogenous ACTH administration but no increase is seen in CPAI patients. Raised plasma ACTH levels confirm adrenal origin of the disease. ## Differential diagnosis Secondary adrenal insufficiency needs to be eliminated. Causes include pituitary tumors (see this term), lymphatic hypophystitis, pituitary tuberculosis and sarcoidosis (see this term), all of which are differential diagnoses. ## Management and treatment Management is life-long and requires a multidisciplinary team. Glucocorticoid replacement with oral hydrocortisone (10-25 mg daily taken in 2-3 doses) is given to mimic physiological cortisol secretion patterns. Oral fludrocortisone is given to replace mineralocorticoid hormones. Dehydroepiandrosterone replacement is optional. Glucocorticoid levels can be adjusted during times of stress to prevent AAI. The dose of hydrocortisone is maintained on the basis of clinical assessment and responses, taking into account a patient's well-being and presence of signs of over-replacement or under-replacement. An assessment of plasma renin activity is helpful in optimizing the dose of fludrocortisone. Growth and development in children must be monitored. Patients should carry a ready to inject hydrocortisone preparation and wear a medical alert card, in case of adrenal crisis. ## Prognosis There is no cure for CPAI but with proper treatment and care taken to prevent AAI there is no decrease in life expectancy. CPAI is only life threatening when ignored. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 primary adrenal insufficiency	c0001403	30,003	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101959	2021-01-23T17:51:53	{"mesh": ["D000224"], "umls": ["C0001403"], "synonyms": ["CPAI", "Chronic adrenocorticoid insufficiency"]}
Abortion in Nicaragua is completely illegal. Prior to a change in the law, which took effect on 18 November 2006, the law allowed pregnancies to be terminated for "therapeutic" reasons, but this clause is no longer in effect.[1] ## Contents * 1 Abortion law in Nicaragua * 2 "Rosa" * 3 Public opinion * 4 Results of the ban * 5 See also * 6 References ## Abortion law in Nicaragua[edit] The law before November 2006 permitted therapeutic abortion in Nicaragua so long as the woman and three doctors consented to it. The definition of "therapeutic" was not specific but was commonly understood to apply to cases in which the pregnant woman's life is endangered.[2] The law prior to November 2006 held that anyone who performed an abortion upon a woman without her permission would be subject to a prison term of three to six years. If the woman consented, both she and the person who performed the abortion faced a sentence of one to four years, and if she attempted a self-induced abortion, the term of imprisonment was four to eight years. A person who performed, or attempted to perform, an abortion, and, as a result, caused injury to the pregnant woman would be jailed for four to 10 years, or six to 10 years if it caused her death.[2] In October 2006, right before the general elections on 5 November 2006, the National Assembly passed a bill further restricting abortion 52-0 (9 abstaining, 29 absent). The European Union and the United Nations had urged for the vote to be delayed until after the presidential elections. The new law outlawed abortion in all circumstances, making Nicaragua the sixth country in the world to do so, after Chile, the Dominican Republic, El Salvador, Malta, and Vatican City. The Assembly rejected a proposal which would have increased the penalty for performing an illegal abortion from 10 to 30 years in prison. President Enrique Bolaños supported this measure, but signed the bill into law on 17 November 2006. Pro-choice groups in Nicaragua have criticized the change to the country's abortion law, and one, the Women's Autonomous Movement, were prepared to file an injunction to prevent it from being enacted.[3][4][5] ## "Rosa"[edit] One case of a termination which was permitted under the former exception to Nicaragua's ban upon abortion was that of a nine-year-old girl, known to the media only as "Rosa," who was impregnated as the result of child sexual abuse in 2003. The child's family, who were living in Costa Rica at the time, returned to Nicaragua after Costa Rican hospital officials had opposed their desire to end the girl's pregnancy. After the family successfully sought an abortion in a private clinic, the Health Minister of Nicaragua, Lucía Salvo, declared that the procedure had constituted a criminal act, and officials threatened to press charges against those involved. However, Attorney General María del Carmen Solórzano stated that the abortion had not violated the law, as it had been performed in the interest of preserving the life of the girl. Rosa's case drew international attention and prompted intense debate about abortion law within Nicaragua. Archbishop Miguel Obando y Bravo of Managua said that the family and doctors involved in obtaining the abortion had excommunicated themselves from the Roman Catholic Church; bishops in Nicaragua also released an open letter which likened the termination of pregnancy to terrorist bombings. Others called for the country's laws to be liberalized.[6][7] ## Public opinion[edit] An August–September 2006 Greenberg Quinlan Rosner Research poll on abortion to save the life of the mother found that 20% of Nicaraguans felt strongly that it should be "legal", 49% felt somewhat that it should be "legal", 18% felt strongly that it should be "illegal", and 10% felt somewhat that it should be "illegal".[8] ## Results of the ban[edit] A report on the effects was filed by the Human Rights Watch in October 2007. Human Rights Watch reports the deaths of at least eighty Nicaraguan women in the eleven months following the ban. To compile the report, interviews were conducted with health officials, women in need of health services, doctors in public health, doctors in the private healthcare system, and family members of women who died as a result of the ban. An unintended side effect has been a "chilling" of other forms of obstetrical care for women. The report states, "While no doctors have been prosecuted for the crime of abortion, as far as we know, the mere possibility of facing criminal charges for providing lifesaving health services has had a deadly effect... the Health Ministry does not monitor the full implementation of the protocols, does not systematize complaints received for the delay or denial of care, and so far has not studied the impact of the law on the lives and health of women." The report quotes an obstetrician as saying "since the law was signed, [public hospitals] don’t treat any hemorrhaging, not even post-menopausal hemorrhaging." Nicaragua’s Health Ministry officials told Human Rights Watch that they did not have any official documentation of the effects of the blanket ban and no plans for gathering such documentation. Consequently, statements that the ban has not caused women's deaths can not be substantiated. By contrast, the report cites several case histories. News reports put the number of deaths at 82 after the law has been in effect less than a year.[9] The point of view of Human Rights Watch is that the law intentionally denies women access to health services essential to saving their lives, and is thus inconsistent with Nicaragua’s obligations under international human rights law to ensure women’s right to life. Their report is called, "Over Their Dead Bodies."[10] ## See also[edit] * Abortion in Chile was also illegal without exception until 2017 * Abortion in El Salvador is also illegal without exception. * Abortion law ## References[edit] 1. ^ "Nicaraguan leader signs abortion law ." (20 November 2006). The Guardian. Retrieved 13 March 2008. 2. ^ a b United Nations Population Division. (2002). Abortion Policies: A Global Review. Retrieved 14 July 2006. 3. ^ "Nicaragua votes to ban abortions." (26 October 2006). BBC News. Retrieved October 29, 2006. 4. ^ "Ban on abortion OKd as expected." (October 27, 2006). Los Angeles Times. Retrieved 29 October 2006. 5. ^ "Nicaragua set to ban all abortions." (October 27, 2006). CBC News. Retrieved 29 October 2006. 6. ^ Miles, Nick. "Abortion ruling splits Nicaragua." (4 March 2003). BBC News. Retrieved 29 October 2006. 7. ^ "Nicaragua Shaken By Child's Abortion." (23 March 2003). CBS News. Retrieved 29 October 2006. 8. ^ "Nicaraguans Favour Abortion in Some Cases Archived January 28, 2007, at the Wayback Machine." (December 4, 2006). Angus Reid Global Monitor. Retrieved January 10, 2006. 9. ^ Khaleeli, Homa. "Killer Law." (8 October 2007). The Guardian Retrieved 11 February 2008. 10. ^ "Møllmann, Marianne". "Over Their Dead Bodies: Denial of Access to Emergency Obstetric Care and Therapeutic Abortion in Nicaragua (PDF). (2 October 2007). "Human Rights Watch, Volume 19, No. 2(B)." Retrieved 11 February 2008. * v * t * e Abortion in North America Sovereign states * Antigua and Barbuda * Bahamas * Barbados * Belize * Canada * Costa Rica * Cuba * Dominica * Dominican Republic * El Salvador * Grenada * Guatemala * Haiti * Honduras * Jamaica * Mexico * Nicaragua * Panama * Saint Kitts and Nevis * Saint Lucia * Saint Vincent and the Grenadines * Trinidad and Tobago * United States Dependencies and other territories * Anguilla * Aruba * Bermuda * Bonaire * British Virgin Islands * Cayman Islands * Curaçao * Greenland * Guadeloupe * Martinique * Montserrat * Puerto Rico * Saint Barthélemy * Saint Martin * Saint Pierre and Miquelon * Saba * Sint Eustatius * Sint Maarten * Turks and Caicos Islands * United States Virgin Islands * 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 * 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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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 Nicaragua	None	30,004	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Nicaragua	2021-01-18T18:47:12	{"wikidata": ["Q2653935"]}
Scrofuloderma Other namesTuberculosis cutis colliquativa[1] SpecialtyDermatology, Infectious disease Scrofuloderma is a skin condition caused by tuberculous involvement of the skin by direct extension, usually from underlying tuberculous lymphadenitis.[2]:335 ## See also[edit] * Scrofula * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. Chapter 74. ISBN 978-1-4160-2999-1. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. ## External links[edit] * Media related to Scrofuloderma at Wikimedia Commons Classification D * ICD-10: A18.4 (ILDS A18.462) * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Scrofuloderma	c0275934	30,005	wikipedia	https://en.wikipedia.org/wiki/Scrofuloderma	2021-01-18T18:46:38	{"mesh": ["D014382"], "icd-10": ["A18.4"], "wikidata": ["Q7439268"]}
A rare bacterial infectious disease caused by Mycobacterium tuberculosis, characterized by a variable clinical picture comprising classic manifestations of meningitis, i. e. headache, fever, and stiff neck, in addition to cranial nerve palsies (most commonly III, VI, and VII), altered mental status, and seizures, among others. Basal meningeal enhancement in neuroimaging, cerebrospinal fluid abnormalities (moderate lymphocytic pleocytosis, moderately elevated protein concentration, low glucose), and a chest x-ray suggestive of pulmonary tuberculosis may support the diagnosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Tuberculous meningitis	c0041318	30,006	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=499004	2021-01-23T17:54:25	{"mesh": ["D014390"], "synonyms": ["TBM", "Tubercular meningitis"]}
Factor VII deficiency is a rare bleeding disorder that varies in severity among affected individuals. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in infancy. However, up to one-third of people with factor VII deficiency never have any bleeding problems. Factor VII deficiency commonly causes nosebleeds (epistaxis), bleeding of the gums, easy bruising, and prolonged or excessive bleeding following surgery or physical injury. Bleeding into joint spaces (hemarthrosis) and blood in the urine (hematuria) occasionally occur. Many women with factor VII deficiency have heavy or prolonged menstrual bleeding (menorrhagia). Severely affected individuals have an increased risk of bleeding inside the skull (intracranial hemorrhage) or in the gastrointestinal tract, which can be life-threatening. Although factor VII deficiency is primarily associated with increased bleeding, some people with the condition have excessive blood clotting (thrombosis). ## Frequency Factor VII deficiency is estimated to affect 1 in 300,000 to 1 in 500,000 people. It is the most frequently occurring of a group of disorders classified as rare bleeding disorders. ## Causes The inherited form of factor VII deficiency, known as congenital factor VII deficiency, is caused by mutations in the F7 gene, which provides instructions for making a protein called coagulation factor VII. This protein plays a critical role in the coagulation system, which is a series of chemical reactions that forms blood clots in response to injury. These mutations reduce the amount of coagulation factor VII in the bloodstream. Such a reduction prevents blood from clotting normally, causing episodes of excessive bleeding. It is not known why some people with this condition have problems with thrombosis. Researchers are also do not know what determines the severity of the condition; it does not appear to be related to the amount of coagulation factor VII in the bloodstream. The noninherited form of the disorder, called acquired factor VII deficiency, is less common than the congenital form. It can be caused by liver disease or by blood cell disorders such as myeloma or aplastic anemia. Acquired factor VII deficiency can also be caused by certain drugs such as medicines that prevent clotting, or by a deficiency of vitamin K. ### Learn more about the gene associated with Factor VII deficiency * F7 ## Inheritance Pattern Congenital factor VII deficiency is inherited in an autosomal recessive pattern, which means both copies of the F7 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. Acquired factor VII deficiency is not inherited. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Factor VII deficiency	c0015503	30,007	medlineplus	https://medlineplus.gov/genetics/condition/factor-vii-deficiency/	2021-01-27T08:25:41	{"gard": ["2238"], "mesh": ["D005168"], "omim": ["227500"], "synonyms": []}
## Clinical Features Mollica et al. (1972) described 2 sisters and a brother with short stature, mental retardation, small head, and ocular abnormalities (iris hypoplasia, nuclear cataracts, severe myopia). Birth weights were not given. The parents, apparently unrelated, were from the same small village in Sicily. HEENT \- Small head \- Ocular abnormalities \- Iris hypoplasia \- Nuclear cataracts \- Severe myopia Growth \- Short stature Neuro \- Mental retardation Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DWARFISM, MENTAL RETARDATION, AND EYE ABNORMALITY	c0796076	30,008	omim	https://www.omim.org/entry/223540	2019-09-22T16:28:35	{"mesh": ["C535809"], "omim": ["223540"], "synonyms": ["Alternative titles", "MOLLICA SYNDROME"]}
Wagner and Hall (1967) reported 2 brothers and a sister with congenital atrioventricular dissociation. They emphasized that this is distinct from A-V block. In dissociation the abnormality seems to be 'lazy' sinoatrial pacemaker with the A-V node taking over intermittently by default. In A-V block an impediment to A-V conduction exists. See heart block (113900, 140400, 234700) and nodal rhythm (163800). Inheritance \- Autosomal recessive Cardiovascular \- Atrioventricular dissociation, congenital \- Sinoatrial pacemaker slowed \- A-V nodal rhythm intermittent ▲ 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	ATRIOVENTRICULAR DISSOCIATION	c0004331	30,009	omim	https://www.omim.org/entry/209600	2019-09-22T16:30:36	{"mesh": ["D006327"], "omim": ["209600"], "icd-10": ["I45.89"], "synonyms": ["Alternative titles", "A-V DISSOCIATION"]}
Grange syndrome is characterised by stenosis or occlusion of multiple arteries (including the renal, cerebral and abdominal vessels), hypertension, brachysyndactyly, syndactyly, increased bone fragility, and learning difficulties or borderline intellectual deficit. Congenital heart defects were also reported in some cases. ## Epidemiology So far, the syndrome has been reported in six patients from three families. ## Genetic counseling The mode of transmission remains unclear, both autosomal recessive and autosomal dominant inheritance with decreased penetrance and parental gonadal mosaicism have been proposed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Grange syndrome	c1865267	30,010	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79094	2021-01-23T18:04:21	{"mesh": ["C566529"], "omim": ["602531"], "umls": ["C1865267"], "icd-10": ["Q87.8"], "synonyms": ["Grange occlusive arterial syndrome", "Progressive arterial occlusive disease-hypertension-heart defects-bone fragility-brachysyndactyly syndrome"]}
Behavioral variant of frontotemporal dementia (bv-FTD) is a form of frontotemporal dementia (FTD; see this term), characterized by progressive behavioral impairment and a decline in executive function with frontal lobe-predominant atrophy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Behavioral variant of frontotemporal dementia	c0236642	30,011	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=275864	2021-01-23T19:05:36	{"mesh": ["D020774"], "omim": ["172700", "600274", "600795", "616437"], "icd-10": ["G31.0"], "synonyms": ["bv-FTD"]}
Secondary polycythemia is an elevated absolute red blood cell mass caused by enhanced stimulation of red blood cell production by an otherwise normal erythroid lineage that may be congenital or acquired (congenital secondary polycythemia and acquired secondary polycythemia; see these terms). ## Epidemiology Prevalence is unknown. ## Clinical description Clinical features vary according to the origin of the disease but may include plethora or ruddy complexion, headache and tinnitus. The congenital form may be complicated by superficial or deep vein thrombophlebitis, or present with associated symptoms as in Chuvash erythrocytosis (see this term), or the course of the disease may be indolent. Patients with a specific sub-type of congenital secondary polycythemia, known as Chuvash erythrocytosis, present with lower systolic or diastolic blood pressure, venous varicosities, and vertebral body hemangiomas and may be complicated by cerebrovascular events or mesenteric thrombosis. The acquired form of secondary polycythemia may present with cyanosis, hypertension, clubbing of the fingers and toes and lethargy. ## Etiology Secondary polycythemia may be congenital and caused by defects in the oxygen sensing pathway due to autosomal recessive mutations in the VHL, EGLN1 and EPAS1 genes (3p26-p25, 1q42-q43 and 2p21-p16 respectively) which result in enhanced erythropoietin (EPO) production in hypoxic conditions, or by other autosomal dominant congenital defects including high oxygen-affinity hemoglobin and biphosphoglycerate mutase deficiency, which result in tissue hypoxia and a secondary erythrocytosis. Alternatively, secondary polycythemia may be acquired and caused by increased amounts of EPO. This may be due to tissue hypoxia that may be central and caused by pulmonary or cardiac disease or high altitude, or local and caused by hypoxia in the kidney such as renal artery stenosis. EPO production may be pathologic and caused by EPO secreting tumors such as renal cell cancer, hepatocellular carcinoma, cerebellar hemangioblastoma, meningioma and parathyroid carcinoma/adenoma (see these terms). In addition EPO may be administered deliberately to produce erythrocytosis and enhance performance. ## Diagnostic methods Diagnosis is based on evidence of increased total red blood cells and normal to high serum EPO levels. Secondary causes of erythrocytosis must be diagnosed individually and will require a comprehensive history. ## Differential diagnosis Differential diagnoses include polycythemia vera and primary familial polycythemia (see these terms), which can be excluded on the basis of low EPO levels and the presence of a mutation in the JAK2 gene (9p24) for polycythemia vera. ## Management and treatment There is little evidence to guide management of congenital secondary polycythemia. Phlebotomy or venesection may be of benefit, particularly in patients at increased risk of thrombosis. A target hematocrit (Hct) of 50% may be the most practical. In patients with no specific contraindication, low-dose aspirin may be of benefit. In acquired cases of secondary polycythemia, management is based on treating the underlying condition. ## Prognosis Prognosis depends mainly on the associated disease in the acquired forms of secondary erythrocytosis and on the severity of thrombotic complications in the inherited forms such as in Chuvash erythrocytosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Secondary polycythemia	c1318533	30,012	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98428	2021-01-23T17:17:40	{"umls": ["C1318533"], "icd-10": ["D75.1"], "synonyms": ["Secondary erythrocytosis"]}
North Carolina macular dystrophy (NCMD) is a non-progressive autosomal dominant macular disorder of congenital or infantile onset characterized by loss of central vision, the accumulation of drusen in the macula and atrophy of photoreceptor cells with a variable phenotype at macular examination. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	North Carolina macular dystrophy	c0730294	30,013	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75327	2021-01-23T18:56:21	{"gard": ["9179"], "mesh": ["C537835"], "omim": ["136550"], "umls": ["C0730294"], "icd-10": ["H35.5"], "synonyms": ["CAPE dystrophy", "CAPED", "Central areolar pigment epithelial dystrophy", "Central retinal pigment epithelial dystrophy", "MCDR1", "NCMD", "North Carolina macular dystrophy, retinal 1", "Progressive foveal dystrophy"]}
Follicular lymphoma Micrograph of a follicular lymphoma, showing the characteristically abnormal lymphoid follicles that gave the condition its name. H&E stain. SpecialtyHematology and oncology Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid tissues such as lymph nodes. The cancerous cells in FL typically form follicular or follicle-like structures (see adjacent Figure) in the tissues they invade. These structures are usually the dominant histological feature of this cancer.[1] There are several synonymous and obsolete terms for FL such as CB/CC lymphoma (centroblastic and centrocytic lymphoma), nodular lymphoma,[2] Brill-Symmers Disease, and the subtype designation, follicular large-cell lymphoma.[3] In the US and Europe, this disease is the second most common form of non-Hodgkin's lymphomas, exceeded only by diffuse large B-cell lymphoma.[4] FL accounts for 10-20% of non-Hodgkin's lymphomas with ~15,000 new cases of it being newly diagnosed each year in the US and Europe.[5] Recent studies indicate that FL is similarly prevalent in Japan.[6] FL is a broad and extremely complex clinical entity with a wide range of manifestations[7] which have not yet been fully systematized.[8] It is commonly preceded by a benign precancerous disorder in which abnormal centrocytes and/or centroblasts accumulate in lymphoid tissue. They may then circulate in the blood to cause an asymptomatic condition termed in situ lymphoid neoplasia of the follicular lymphoma type (i.e. ISFL). A small percentage of these cases progress to FL.[9] Most commonly, however, FL presents as a swelling of lymph nodes in the neck, armpits, and/or groin. Less often, it presents as a gastrointestinal tract cancer, a cancer in children involving lymphoid tissues of the head and neck area (e.g. tonsils),[10] or one or more masses in non-lymphoid tissues such as the testes.[11] FL typically has a slow disease course which persists essentially unchanged for years.[7] However, each year 2-3%[12] of FL cases progress to a highly aggressive form often termed stage 3B FL, to an aggressive diffuse large B-cell lymphoma, or to another type of aggressive B-cell cancer. These transformed follicular lymphomas (t-FL) are essentially incurable.[5] However, recent advancements in the treatment of t-FL (e.g. the addition to standard chemotherapy of agents such as rituximab) have improved overall survival times. These newer regimens may also delay the transformation of FL to t-FL.[5] Additional advances in understanding FL may lead to further improvements in treating the disease.[12][13] ## Contents * 1 Pathophysiology * 1.1 Genomic alterations * 1.1.1 In situ follicular lymphoma * 1.1.2 Follicular lymphoma * 1.1.3 Transformed follicular lymphoma * 1.2 Tumor environment * 2 Presentation and course * 2.1 In situ follicular lymphoma * 2.2 Follicular lymphoma * 2.2.1 Duodenal-type follicular lymphoma * 2.2.2 Primary gastrointestinal tract follicular lymphoma * 2.2.3 Predominantly diffuse follicular lymphoma with 1p36 deletion * 2.2.4 Pediatric-type follicular lymphoma * 2.2.5 Primary follicular lymphoma of the testis * 2.3 Transformed follicular lymphoma * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment and prognosis * 4.1 In situ follicular lymphoma * 4.2 Localized follicular lymphoma * 4.3 Asymptomatic follicular lymphoma * 4.4 Symptomatic follicular lymphoma * 4.5 Transformed follicular lymphoma * 4.5.1 Prevention * 4.6 Relapsed follicular lymphoma * 5 See also * 6 References * 7 External links ## Pathophysiology[edit] ### Genomic alterations[edit] The serial progressions of in situ FL to FL and FL to t-FL appear to involve the accumulation of increasing numbers of genomic alterations (i.e. chromosome abnormalities and gene mutations) in the formative B-cell precursors to these disorders. At least some of these alterations appear to cause the over-expression or under-expression of the products of genes that regulate these cells' susceptibility to develop further genomic alterations, to survive, to proliferate, and/or to spread to other tissues. In consequence, multiple B-cell clones that exhibit increasing genomic alterations and malignant behaviors populate the disorder. No single genomic alteration seems responsible for the development of each of the spectrum of FL disorders. Rather, interactions between multiple genomic alterations appear to underlie this serial progression.[5][12] #### In situ follicular lymphoma[edit] In situ follicular lymphoma is an accumulation of monoclonal B cells (i.e. cells descendent from a single ancestral cell) in the germinal centers of lymphoid tissue. These cells commonly bear an pathological genomic abnormality, i.e. a translocation between position 32 on the long (i.e. "q") arm of chromosome 14 and position 21 on chromosome 18's q arm. This translocation juxtaposes the B-cell lymphoma 2 (BCL2) gene on chromosome 18 at position q21.33 near to the immunoglobulin heavy chain locus (IGH@) on chromosome 14 at position q21. In consequence, BCL2 overexpresses its product, BCL2 apoptosis regulator (i.e. Bcl2). Bcl2 functions to inhibit programmed cell death thereby prolonging cell survival.[14] The overexpression of Bcl2 in the B-cells of ISFL is thought to be a critical factor in their pathological accumulation and subsequent malignant progression.[9] Small numbers (e.g. 1 in 100,000) of circulating nucleated blood cells bearing this t(14:18)q32:q21) translocation are found in 50-67% of otherwise healthy individuals. The prevalence of this finding increases with age and years of tobacco smoking. Since most individuals with this translocation in their blood cells do not develop ISFL, the t(14:18)(q32:q21) translocation, while prolonging cell survival, must be just one step in the development of ISFN. This translocation is proposed to occur during the early development of immature bone marrow B-cells (i.e. pre-B-cells/pro-B-cells) after which these cells circulate freely and in rare cases accumulate and mature to centrocytes and/or centroblasts in the germinal centers of lymphoid follicles to form ISFL. The mechanism favoring this localization and further accumulation is unclear.[15] Individuals with ISFL progress to FL at a rate of 2-3%/year for at least the first 10 years following diagnosis.[12] This progression likely involves the acquisition of genomic aberrations besides the t(14:18)q32:q21) translocation in the ISFL B-cells. Suspect mutations include those in the following genes: 1) EZH2 (encodes polycomb repressive complex 2 family protein which is involved in maintaining the transcriptional repressive state of various genes[16] and is found in up to 27% of FL cases);[9] 2) CREBBP (encodes CREB-binding protein which contributes to the activation of various genes[17]); 3) TNFSF14 (encodes tumor necrosis factor superfamily member 14, a member of the tumor necrosis factor superfamily which may function as a co-stimulatory factor for the activation of lymphoid cells[1][18]); and 4) KMT2D (encodes histone-lysine N-methyltransferase 2D, a histone methyltransferase which regulates the expression of various genes[19]).[20] ISFL may also acquire numerous copy-number variations (i.e. duplications and deletions of a portion of a chromosome along with any of the genes contained therein) that may contribute to FL. In all cases, the number of genetic abnormalities acquired in the B-cells of ISFL are much less than those in FL.[9] #### Follicular lymphoma[edit] The genomic alterations found in FL include 1) the t(14:18)(q32:q21.3) translocation (85-90% of cases); 2) 1p36 deletions (i.e. deletions in the q arm of chromosome 1 at position 36, [60-70% of cases]) that lead to lose of TNFAIP3 (encodes tumor necrosis factor, alpha-induced protein 3 which inhibits the activation of NF-κB, blocks cell death due to apoptosis, and regulates lymphocyte-based immune responses through its ubiquitin ligase activity[21]); 3) mutations in PRDM1 (encodes the PR domain zinc finger protein which promotes the maturation and proliferation of B-cells);[22] and 4) the same mutations seen in ISFL including KMT2D (85-90% of cases), CREEBP (40-65% of cases), BCL2 (40-65% of cases), and EZH2 (20-30% of cases) as well as other mutations such as those in the histone-modifying gene HIST1H1E (20-30% of cases), the RRAGC gene (~17% of cases) which regulates cell growth, survival, death, and proliferation,[23] and, in ≤15% of cases several other genes including MEF2B, STAT6, EP300, ARID1A, SLC22A2, CARD11, FOXO1, GNA12, B2M (i.e. the gene for beta-2 microglobulin), and SGK1. Except for the t(14:18)(q32:q21.3) translocation and EZH2 mutations which lead to gains in the expression and function, respectively, of their products, the genetic alterations generally lead to a loss in the production or function of the cited genes products. However, the exact roles, if any, of these genomic abnormalities in promoting the progression of ISFL to FL are unclear.[24] #### Transformed follicular lymphoma[edit] The transformation of FL to a more aggressive state or other type of aggressive lymphoma is associated with: 1) primarily gene-activating mutations in CREEBP, KMT2D, STAT6, CARD11 (encoding a guanylate kinase which interacts with BCL10 and activates NF-κB to regulate cell survival); 2) changes in the expression of diverse genes; 3) the overproduction of various cell-activating cytokines[25] and CD79B (encoding the Ig-beta protein component of the B-cell receptor[26]); 4) gene-inactivating mutations in TNFAIP3, CD58 (encoding the cell adhesion molecule, lymphocyte function-associated antigen 3, that is involved in activating T-cells[27]), CDKN2A (encoding p16INK4a and p14arf tumor suppressor proteins[28]) or CDKN2B (encoding cyclin dependent kinase inhibitor 2B multiple tumor suppressor 2[29]) (inactivation of either CDKN2 gene causes genome instability, i.e. increased frequency of other gene mutations), and TNFRSF4 (encoding one type of tumor necrosis factor receptor[30]); and 5) gene-activating or -inactivating mutations in, or other causes for the under- or over-expression of, c-MYC ((encoding the c-Myc proto-oncogene transcription factor that regulates the expression of diverse genes many of which promote cell proliferation[31]).[24] ### Tumor environment[edit] The non-neoplastic immune and stromal cells as well as the extracellular matrix in tissues may enable neoplastic follicular cells to survive, proliferate, and avoid surveillance by the immune system. For example, laboratory studies show that: 1) follicular dendritic cells, fibroblastic reticular cells, and T helper cells provide growth and survival signals to neoplastic follicular B-cells; 2) neoplastic follicular B-cells recruit regulatory T cells that act to suppress immune responses to them; 3) the cytotoxic T-cells which normally kill neoplastic cells become dysfunctional in the presence of neoplastic follicular cells that are embedded in this multicellular environment; and 4) bone marrow stromal cells directly support the growth of neoplastic follicular cells.[24] Reduced levels of immune-infiltration has been shown to be strongly associated with early progression of disease.[32] ## Presentation and course[edit] ### In situ follicular lymphoma[edit] FL is commonly preceded by but uncommonly progresses to ISFL, an asymptomatic disorder that usually is discovered in tissues which are biopsied for other reasons. FL lymphoma may be diagnosed in the uncommon cases in which individuals with ISFL are found to have FL on follow-up examinations.[9] Similarly, individuals with >1 in 10,000 circulating lymphocytes containing the t(14:18)q32:q21) translocation are at increased but still small risk of developing FL and being diagnoses as having FL on follow up examinations.[10] ### Follicular lymphoma[edit] FL commonly presents as an otherwise asymptomatic enlargement of lymph nodes in the neck, armpit, groin,[13] femoral canal,[33] or other sites in individuals (median age 65) without a known history of ISFL or abnormal numbers of circulating t(14:18)q32:q21-conatianing lymphocytes.[13] These enlargements may have been present for months to years and during this time waxed and waned in size.[8] Less commonly, FL presents as extra-nodal masses in the skin, thyroid gland, salivary gland, breast, testicles.[11] spleen, liver,[33] and/or lung.[4] Regardless of the type of presentation, FL is usually (~80% of cases[8]) at an advanced stage at diagnosis as indicated by involvement of the bone marrow (50%[13] to 70%[8] of cases), multiple lymph nodes in different parts of the body,[9] and/or other tissues.[11] A minority (<33%)[8] of FL patients present with B symptoms, i.e. recurrent unexplained fevers, recurrent night sweats, and/or weight loss ≥10% in the past 6 months.[5] Generally, the disease has an indolent and prolonged course with a median life expectancy of 15–20 years: a large percentage of patients die from other causes than their FL disease.[5] However, each year, including the early years after diagnosis, some 2-3% of FL cases transform to t-FL;[12] Median survival has been ~4.5 years after the onset of this transformation.[5] There are less common subtypes of FL that differ not only in their presentation but also in their histopathology, genetic abnormalities, and course. These subtypes, which are now (i.e. primary gastrointestinal tract FL) or may in the future (pediatric-type FL) be considered distinctive diseases, are: #### Duodenal-type follicular lymphoma[edit] Main article: Duodenal-type follicular lymphoma Duodenal-type follicular lymphoma (DFL) was initially considered to be a type of Primary gastrointestinal tract (GI tract) follicular lymphoma (PGTFL), i.e. a follicular lymphoma in which GI tract lesions were prominent parts of the disease.[34] However, a subset of PGTFL cases had lesions that were localized to the duodenum and other parts of the small intestine usually without involving other parts of the GI tract or tissues outside of the GI tract. This contrasts with the other cases of PGTFL which were systemic diseases involving a wide range of GI tract and non-GI tract tissues. Consequently, the World Health Organization (2017) removed the localized disease from the primary gastrointestinal tract follicular lymphoma category, reclassified it as a distinct disease entity, and termed it duodenal-type follicular lymphoma.[6] DFL is most often an asymptomatic disease that is diagnosed on endoscopic examination of the GI tract conducted for other reasons. Less commonly, it presents with vague abdominal symptoms.[35][36] In one review of former studies, the lesions in 85% of primary duodenal follicular lymphoma were located not only in the duodenum but also other sites in the intestine (i.e. jejunum and/or ileum),[11] with rare cases having lesions in the rectum[37] or cecum[38] PDF is an indolent disease that may spontaneously remit and relapse but only rarely progresses to a more aggressive form. A watch-and-wait strategy has been a generally recommended method for the initial treatment of the disease.[39] #### Primary gastrointestinal tract follicular lymphoma[edit] PGTFL is a follicular lymphoma (which as currently defined excludes cases of duodenal-type follicular lymphoma) that has a prominent component of GI tract involvement. The disease may present with signs and symptoms typical of the common type of follicular lymphoma. For example, enlargement of lymph nodes in the neck, armpit, groin,[13] femoral canal, and/or other areas,[33] and/or signs and symptoms of GI tract disease[34] due to lesions in the stomach, small intestine, large intestine[11] or rectum may be seen.[37] These signs and symptoms may include abdominal pain, bowel obstruction,[11] persistent nausea and vomiting, hematochezia (i.e. passage of fresh blood usually on feces through the rectum), or melena (i.e. passage of tarry feces containing blood that has been digested in the stomach or upper intestine).[40] PGTFL is generally treated like cases of common follicular lymphoma: depending on the severity of the disease and its symptoms, patients are treated with watchful waiting, surgery, chemotherapy, radiation, immunotherapy plus radiotherapy, or combinations of these modalities.[41] #### Predominantly diffuse follicular lymphoma with 1p36 deletion[edit] Predominantly diffuse follicular lymphoma with 1p36 deletion is a rare subtype of FL[7] in which involved lymph nodes show infiltrations of centrocytes and centoblasts that generally do not form the nodular, swirling patterns characteristic of most types of FL.[1] In addition, these cells lack the t(14:18)(q32:q21.3) translocation commonly found in other FL types but, similar to many FL cases, have a deletion in the terminal part of the short (i.e. "p") arm of chromosome 1 that encodes the TNFRSF14 gene (see pathophysiology section).[13] Predominantly diffuse follicular lymphoma with 1p36 deletion usually presents with bulky enlargements of inguinal (i.e. groin) lymph nodes but may present with enlargements of the axillary (i.e. armpit) or cervical (i.e., neck) lymph nodes. In rare cases, there may be involvement of the bone marrow. In spite of the evidence of bulky and disseminated disease, predominantly diffuse follicular lymphoma with 1p36 deletion appears to be an indolent disorder that may require long-term observation rather than overtreatment.[7] #### Pediatric-type follicular lymphoma[edit] Main article: Pediatric-type follicular lymphoma Pediatric-type follicular lymphoma (PTFL) was initially reported to occur in children ages 1–17 years old (median age ~13-14) but more recently has been reported to occur in adults.[42] The disorder was recently defined by the World Health Organization (2016) as a distinct entity that occurs mostly in males[7] and involves swollen lymph nodes in the head (including tonsils and adenoids), neck,[42] or, rarely, axillary, or inguinal areas, or non-lymphoid tissues.[43] Currently, however, patients who had exhibited or are exhibiting involvement of areas or tissues outside of the head, neck, armpit, or groin areas are now regarded as far more likely to have a newly and provisionally defined disease, large B-cell lymphoma with IRF4 rearrangement.[42] The lesions in PTFL consists of infiltrates containing rapidly proliferating centrocytes and centroblasts that lack the t(14:18)(q32:q21.3) translocation but nonetheless often overexpress the BCL2 gene.[7] These cells may show a loss of heterozygosity at 1p36 (20-50% of cases) that results in decreased expression of the TNFRSF14 gene (see Pathophysiology section) as well as mutations in the IRF8 (10-50% of cases), which contributes to the development and function of B cells,[44][45] and the MAP2K1 gene (10-40% of cases), which regulates activation of the ERK cell signaling pathway.[46] More than 2 dozen other genes have been reported to be mutated in rare cases of PTFL but in general the genetic abnormalities found in this disorder are fewer and less complex than those in other types of FL.[43] PTFL has an indolent, relapsing and remitting course with a 5-year survival rate of >95%.[43] Patients diagnosed with PTFL have been treated with chemotherapy, surgery, and combinations of these treatments. In general, these patients did well (100% survival with <5% of cases relapsing regardless of treatment modality). More recently, 36 patients have been treated with surgical resection alone followed by observation; all these patients survived with only one having a relapse. Thus, PTFL appears to be a highly indolent type of FL in which multiple studies have reported overall and progression-free survival rates of 100% and >90%, respectively, for >2 years and an estimated probability of 5-year event-free survival rate of ~96%. The therapeutic regimens versus follow-up observations that best treat this disorder in children, adolescents, and adults (adults may require different treatments than children and adolescents) requires further study.[42] #### Primary follicular lymphoma of the testis[edit] Primary follicular lymphoma of the testis (PFLT), also termed testicular follicular lymphoma, was classified as a distinct form of FL by the World Health Organization in 2016.[33] It is an extremely rare disease that has been recognized as occurring primarily in children and adolescents[47] but also has been reported in 5 adults.[48] PFLT differs from cases of typical follicular lymphoma that involve the testis in that it more often occurs in children and adolescents; involves malignant B-cells that do have the t(14:18)q32:q21) translocation; and presents with disease that is strictly limited to the testis. While similar to pediatric-type follicular lymphoma in not involving cells that bear the t(14:18)q32:q21) translocation, PFLT differs from the former disease in that it is limited to the testis and involves malignant cells that do not express Bcl2.[49] PFTL is an extremely indolent disease which is manifested by lesions that exhibit a typical FL histology or, more commonly, a mixed FL-diffuse large cell lymphoma histology. It usually involves a 2-4 centimeter lesion in a single testicle. Patients have been treated with removal of the involved testes followed by various standard anti-lymphoma chemotherapy regimens to attain excellent results, i.e. 100% completed remissions with no recurrence of disease in 15 child and adolescent patients observed for 4–96 months. No cases of primary follicular lymphoma of the testis have been reported to progress to t-FL. Surgery followed by less strenuous or even no chemotherapy may prove to be the optimal treatment for this disease.[47] ### Transformed follicular lymphoma[edit] FL progresses at a rate of 2-3% per year for at least the first 10 years after diagnosis to a more aggressive form, principally diffuse large B-cell lymphoma (~93% of cases) or Burkitt-like lymphoma (~7% of cases) or in rare cases exhibit the histology resembling precursor B-cell lymphoblastic leukemia, plasmablastic lymphoma, the high grade subtype of B-cell lymphoma, Hodgkin lymphoma of the B-cell type, chronic lymphocytic leukemia/small cell lymphcytic lymphoma,[5] or histiocytic sarcoma.[1] t-FL is almost always diagnosed in patients being followed for FL. These FL patients present with the: fast growth of lymph nodes; formation of extra-nodal lesions in extra-nodal sites such as the central nervous system, liver or bone; the onset of B-symptoms (i.e. fever, night sweats, weight loss); development of hypercalcemia (i.e. high serum levels of calcium); and/or sudden rises in serum levels of the enzyme lactate dehydrogenase.[5] A minority of t-FL patients present without a history of FL. These patients generally present with advanced, bulky disease that may be accompanied by extra-nodal lesions and B-symptoms.[1] Typically, all the various forms of t-FL are aggressive, rapidly progressive diseases with overall media survival times in treated patients of ~4.5 years.[1][5] The transformation of FL to DLBCL is in over 70% of cases associated with the gain of MYC activity by genetic or non-genetic mechanisms.[50] ## Diagnosis[edit] Follicular lymphoma replacing a lymph node; the bubble-like outgrowths are enlarged follicles. The diagnosis of FL depends on examining involved tissues for histological, immunological, and chromosomal abnormalities that are indicative of the disease. FL usually involves enlarged lymph nodes populated by abnormal follicles (see adjacent picture) that when examined histologically contain a mixture of centrocytes or centroblast surrounded by non-malignant cells, mostly T-cells. The centrocytes, which typically outnumber centroblasts, are small to medium-sized B-cell lymphocytes that characteristically exhibit cleaved nuclei; the centropblasts are larger B-cell lymphocytes without cleaved nuclei.[11] Rare cases of FL may show lesions that contain tissue infiltrations dominated by B-cells with features of precursor (i.e. "blast") cells, monocytes, or malignant mantle cells such as those found in mantle cell lymphoma.[1] Immunochemical analyses reveal that the these cells generally express B-cell surface markers including the CD10 (60% of cases), CD20, CD19, CD22, and CD79 but not CD5, CD11c, or CD23 cell surface proteins;[4] genomic analyses reveal that these cells contain t(14:18)(q32:q21.3) translocation (85-90% of cases), 1p36 deletions (60-70% of cases), and with far less frequency the other genomic abnormalities listed in the above sections on Pathophysiology and Presentation and course. None of these protein markers or genomic abnormalities are diagnostic for FL, e.g. the t(14:18)(q32:q21.3) translocation is found in 30% of diffuse large B-cell lymphoma and in a small number of reactive benign lymph nodes. Rather, the diagnosis is made by a combination of histological, immunological, and genomic abnormalities.[4] According to World Health Organization (WHO) criteria, differences in the microscopically-determined morphology of these tissues can be used to diagnose and categorized FL into the following 3 Grades with grade 3 having A and B subtypes:[51] * Grade 1: follicles have <5 centroblasts per high-power field (hpf). * Grade 2: follicles have 6 to 15 centroblasts per hpf. * Grade 3: follicles have >15 centroblasts per hpf. * Grade 3A: Grade 3 in which the follicles contain predominantly centrocytes. * Grade 3B: Grade 3 in which the follicles consist almost entirely of centroblasts. Grades 1 and 2 are regarded as low grade FL; Grade 3A is usually also regarded as low grade FL although some studies have regarded it as high grade FL; and Grade 3B is regarded as a highly aggressive FL in the t-FL category.[8] In addition to grade 3B disease, histologic examinations may reveal other evidence of t-FL such as histologic findings consistent with FL and diffuse large cell lymphoma in the same tissue (referred to as composite lymphomas) or in separate tissues (referred to as (discordant lymphomas) or histologic findings similar to those found in Burkitt lymphoma, precursor B-cell lymphoblastic leukemia, plasmablastic lymphoma, the high grade subtype of B-cell lymphoma, Hodgkin lymphoma of the B-cell type, chronic lymphocytic leukemia/small cell lymphocytic lymphoma,[5] or histiocytic sarcoma.[1] Other findings indicating the presence of this transformation include rapid growth in size of lymph nodes, recently acquired or new B symptoms, recent development of FL lesions in non-nodal tissue, rapid rises in serum lactate dehydrogenase levels, and the presence of high levels of serum calcium.[12] ### Differential diagnosis[edit] FL may be confused with marginal zone B-cell lymphoma, mantle cell lymphoma, and the small lymphocytic lymphoma variant of chronic lymphocytic leukemia. The malignant cells in marginal zone B-cell lymphoma may form follicular structures but commonly proliferate in the marginal zone rather than germinal center of lymphoid tissues. These malignant cells often show features of monocytes or plasma cells. Mantle cell lymphomas show monotonous, medium-sized lymphocytes, monocytes, and atrophied germinal centers; unlike FL, the malignant lymphocytes in this disease are positive for Cyclin D1 by immunohistochemistry staining. Small lymphocytic lymphomas are composed of nodular structures with small- to medium-sized malignant cells surrounding immature lymphocytes and immunoblasts. The malignant cells in this disease, unlike FL, stain positive for CD5 and CD23.[11] ## Treatment and prognosis[edit] FL is typically a slowly growing lymphoma with an overall median life expectancy for treated patients of 10–15 years[34] with many cases of it waxing and waning in the size of their lesions and rare cases of it remitting spontaneously.[4] These considerations favor the use of observation over intervention in patients whose particular form of FL has a favorable prognosis or who are intolerant to aggressive treatments.[4] However, most cases of FL have a less favorable prognosis at some stage of their disease and will therefore require intervention. There is little consensus regarding the guidelines to be used to define the prognosis and treatment for FL at its presentation or during its course.. Currently used indicators for this include the disease's: 1) histology; 2) subtype; 3) predicted indolence and potential for transformation; and 4) extent of disease as measured by clinical examinations, bone marrow biopsy to determine bone marrow involvement, and PET/CT imaging of the chest, abdomen, pelvis, and any areas outside of these regions if physical examination suggests involvement.[52] Some suggested guidelines using these parameters to indicate the prognosis and need for treatment in FL include:[8] * The WHO criteria using histological grade (see previous section): Patients with Grades 1, 2, and 3A disease are predicted to have the same low risk prognosis that is seen in cases of typical FL while patients with grade 3B disease are predicted to have the high risk prognosis typical of t-FL. * The Follicular Lymphoma International Prognostic Index (FLIPI): FLIPI uses the following criteria: age ≥60 years; Ann Arbor disease stage III (i.e. lesions located both above and below the thoracic diaphragm) or IV (i.e. disseminated lesions involving one or more non-lymphatic organs); blood hemoglobin <12 gram/deciliter; serum lactose dehydrogenase level above normal; and involvement of >4 lymph nodes. Patients positive for 0–1, 2, or ≥3 of these factors are classified as in low, intermediate, and high risk group, respectively, and after treatment with regiments that include rituximab have 2 year predicted progression free survivals of 84, 72, and 65%, respectively, and overall survivals of 98, 94, and 87%, respectively.[4] * The FLIP2 index. This modification of FLIP1 uses age ≥60; blood hemoglobin <12 gram/deciliter; serum lactose dehydrogenase level above normal; serum beta-2 microglobulin level above normal; ≥1 lymph node with a diameter >6 centimeters; and bone marrow involvement. The predicted percentage of therapy-treated patients with progression free survival at 5 years for individuals positive for 0, 1–2, and ≥3 of these factors are 80, 51, and 19%, respectively.[8] * CT/PET imaging: This method measures total body tumor volume as detected by tissue uptake of radioactive fludeoxyglucose (F18). Progression free and overall survival at 5 years for patients with estimated tumor volumes above versus below 510 cubic centimeters are reported to be 32.7 and 84.8% versus 65.1 and 94.7%, respectively.[8] * Lugano staging: this method classifies Stage I disease as involving a single lymphatic region or extra-lymphatic site; Stage II disease as involving ≥2 lymphatic sites or 1 lymphatic site plus 1 extralympatic site with all lesions being on the same side of the diaphragm; Stage III disease as involving ≥2 lymphatic regions that are on opposite sides of the diaphragm; and Stage IV disease as disseminated lesions that are found to be in ≥1 non-lymphatic organs.[4] * Response-based prognosis: FL patients whose disease progresses within 24 months of initiating treatment with chemotherapy and immunotherapy versus patients whose disease does not progress within 24 months are predicted to have 5 year survival rates of 50-74% versus ~90%, respectively.[8] The prognosis and treatment for the specific presentations of typical FL cases (see above sections for the prognoses and treatment recommendations for primary gastrointestinal tract FL, predominantly diffuse FL with 1p36 deletion, pediatric-type FL, and primary FL of the testis) that are in common use are as follows: ### In situ follicular lymphoma[edit] ISFL is a benign condition that may be reevaluated periodically to detect the rare cases of it which progress to FL; otherwise ISFL is not treated.[9] ### Localized follicular lymphoma[edit] In 10-20% of cases, FL appears limited to single radiation field, does not involve the bone marrow, and is therefore regarded as localized early-stage FL. In these cases, which are sometimes classified as Ann Arbor stage I (i.e. disease limited to a single restricted region) or stage II (i.e. disease restricted to two sites that are on the same side of the diaphragm),[4] radiation therapy achieves 10 year overall survival rates of 60-80% and median overall survival times of 19 years.[8] It seems likely that many of the relapses in these cases are due to undetected disease outside of the radiation field at the time of radiation treatment. The use of PET/CT imaging is strongly recommended to insure that the FL is localized. In any case, the excellent results achieved with radiation therapy strongly support its use in localized disease. The use of an immunotherapeutic agent such as Rituximab alone or in combination with a chemotherapeutic regimen such as CVP (i.e. cyclophosphamide, vincristine, prednisone and rituximab) in cases of localized, early-stage disease may be appropriate choices for some of these early-stage patients.[4] However, the latter approach is recommended for cases of localized disease in which the disease extends beyond a single field: 56% of patients treated in this manner had progression-free survival at 10 years while patients treated with other regimens had progression free survivals of 41%. Nonetheless, overall survival did not differ between the two groups.[13] ### Asymptomatic follicular lymphoma[edit] Patients with asymptomatic but not localized low grade FL,[8][53][54] gastrointestinal tract FL,[34] and pediatric-type follicular lymphoma[42] have been served by careful follow-up without therapeutic intervention. Even high grade, aggressive, relapsed, or transformed FL may also be served with observation in patients who are asymptomatic. Findings in asymptomatic patients who have been recommended as triggers for starting treatment include one or more of the following: tumor size ≥7 cm in diameter; involvement of ≥3 nodes in 3 distinct areas, each of which is ≥3 cm in diameter; organ compression; presence of ascites or pleural effusion (i.e. build-up of fluid in the abdominal or pleural cavities); poor performance status due to the disease; elevated levels of serum lactose dehydrogenase or beta-2 microglobulin;[4] presence of localized bone lesions; kidney involvement; reduced levels of circulating blood platelets or any of the various types of white blood cells; onset of significant pruritus (i.e. itching sensation) or other B symptoms; and enlargement (i.e. ≥50% increase in size over a period of at least 6 months) of lymph nodes, spleen, or other follicular lymphoma-infiltrated organs or tissues.[33] ### Symptomatic follicular lymphoma[edit] Symptomatic FL requires treatments directed at relieving symptoms by reducing the load of tumor cells. Various chemotherapeutic regimens have been used for this including combinations of alkylating antineoplastic agents, nucleoside analogues, and/or anthracyclines. Two commonly used chemotherapeutic regimens are CVP (see Localized FL section) and CHOP (i.e. CVP plus the anthracycline adriamycin). Newer agents used to treat FL include monoclonal antibodies such as rituximab, obinutuzumab, galiximab, inotuzumab ozogamicin, or epratuzumab and immunomodulators such as lenalidomide and interferon. The latter medications have been used in combination or alone to treat symptomatic FL.[13] Most such regimens add rituximab (a monoclonal antibody which binds and thereby kills the CD20 cell surface protein on B cells) with CVP or CHOP regimens (termed R-CVP and R-CHOP regimens). The R-CHOP regimen appears superior to the R-CVP regimen with, for example, one study finding 8-year progression-free survival rates of 57% versus 46% for the two respective regimens.[33] More recently, FL patients have been treated with other regimens including: 1) rituximab combined with the chemotherapeutic alkylating agent bendamustine; 2) rituximab combined with the chemotherapeutic agent fludarabine and the inhibitor of Type II topoisomerase, mitoxantrone;[33] and 3) rituximab combined with another immunotherapeutic agent such as galiximab, epratuzumab (monoclonal antibodies directed respectively against the CD80 or CD22 cell surface proteins on immune cells including B cells), or the immunomodulating medication, lenalidomide.[13] While it is too soon to judge the long-term results of the latter regimens, the regimens have shown similar results when analyzed based on poor treatment responses (~10-20% poor responses). Bendamustine with rituximab may be preferable to R-CHOP or R-CVP for treating low-grade (i.e. Grades 1, 2, and possibly 3A) FL; R-CHOP may be preferred in FL that has high-risk characteristics (e.g. high levels of Beta-2 macroglobulin or bone marrow involvement). The combination of lenalidomide with rituximab has shown good potential in treating indolent cases of FL.[13] Studies indicate that maintenance therapy with rituximab following successful induction therapy prolongs progression-free survival; for example one study found progression-free survival after 6 years of treatment was 59.2% in patients treated with rituximab maintenance and 42.7% without this maintenance; however, overall survival at 6 years was similar in the two groups, 87.4% and 88.7%, respectively. Another study found that prolonged maintenance with rituximab did not have any benefits over an eight-month maintenance period.[13] Finally, surgery[55][56] and radiation[4][13][33] are additional therapies that can be used to relieve symptoms caused by bulky t-FL disease or to treat lesions in patients who cannot withstand other types of treatment. ### Transformed follicular lymphoma[edit] Early studies on treating t-FL with various purely chemotherapy regimens gave poor results with median overall survival times of 1–2 years. However, the addition of rituximab to the regimens such as CVP and CHOP as part of induction and maintenance therapies (i.e. R-CVP and R-CHOP) greatly improved overall 5 year survival to rates of 73%. The R-CHOP regimen is a good option for treating such cases.[5] However, these regimens need not be started in people with FL who are asymptomatic and have low tumor burdens: the outcomes in such patients show no difference between early versus delayed treatment. Some recent studies found that the use of rituximab in combination with bendamustine (i.e. the RB regimen) provided better results than R-CHOP: progression-free survival times in one study were 69.5 months for RB and 31.2 months for R-CHOP. Similar results were obtained when RB was compared to R-CVP. These studies also found no overall survival time benefit between the RB and R-CHOP regimens. Other recently examined regimens include 1) the use of obinutuzumab instead of rituximab in the R-CHOP and R-CVP regiments to attain progression-free survival rates at 3 years of 80% for the obinutuzumab-chemotherapy regimen versus 73% for the rituximab-chemotherapy regimen and 2) the combination of rituximab with lenalidomide (no chemotherapy agent) versus various chemotherapy plus immunotherapy (principally rituximab) to achieve similar complete remission and 3 year progression-free survival rates but with rituximab plus lenalidomide causing less toxicity (i.e. severe neutropenia). Many of these studies did use rituximab maintenance therapy after induction therapy.[4] #### Prevention[edit] Several studies, while not conclusive, suggest that the early treatment of low risk FL reduces the incidence of the disease progressing to t-FL. The treatments used in these studies include chemotherapy, radiation therapy, and immunotherapy combinations plus rituximab maintenance therapy.[12] ### Relapsed follicular lymphoma[edit] Patients who relapse after initial therapy for FL may be followed closely without therapy if asymptomatic. When treatment is required, patients may be treated with the initial treatment regimen when such treatment led to a remission that lasted for at least one year; otherwise an alternative regimen is used.[13] The regimens commonly used in relapsed lymphoma include R-CHOP, R-CVP, RFM (i.e. rituximab, fludarabine, and mitoxantrone), and RB (Bendamustine plus rituximab).[4] Patients who suffer early treatment failure (e.g. within 1–2 years of initial treatment) or multiple relapses have also been treated with either autologous (i.e. stem cells taken from patient) or allogeneic (i.e. stem cells taken from a donor) stem cell bone marrow transplantation. While studies are inconclusive, autologous stem cell bone marrow transplantation appears to prolong survival in early treatment failure patients who are healthy enough to withstand this therapy. Unfit patients may benefit from initial treatment with obinutuzumab plus bendamustine followed by maintenance treatment with obinutuzumab (if they have not been treated previously with obinutuzumab).[13] Other mostly experimental treatments currently under study in patients with multiple treatment failures include: 1) Phosphoinositide 3-kinase inhibitors such as copanlisib, duvelisib, and idelalisib which block the phosphoinositide 3-kinase signaling pathway that promotes the survival, proliferation, and other potentially malignant behaviors of cells; 2) infusion of tisagenlecleucel chimeric antigen receptor T cells (i.e. CAR T cells) (i.e. T cells that have been isolated from patients, engineered to express a receptor for the CD19 protein on, and thereby kill, T cells, and then infused back into the donor patient);[52] 3) Bruon's tyrosine kinase inhibitor, ibrutinib, to block the B-cell maturating actions of this kianase; 4) BCL inhibitor venetoclax to block Bcl2's action in promoting B-cell survival and proliferation; 5) histone deacetylase inhibitors abexinostat and tazemetostat to modify the expression of various genes; and 6) Checkpoint inhibitors nivolumab, pidilizumab, and pembrolizumab to promote the immune system's ability to suppress cancer cell growth.[4] In preliminary studies on FL patients who were known or thought to be refractor to more conventional therapies these drugs, when combined with more conventional drugs, particularly rituximab, produced promising results. Phosphoionsitide 3-kinase inhibitors produced overall response rates of 10–12.5 months in 42-59%; tisagenlecleuce cells produced an overall progression-free response rate of 70% after a follow-up of 28 months;[52] phosphoinositide 3-kinase inhibitors produced overall response rates of ~40% and complete response rates of 1-20%; Bruton's tyrosine kinase inhibitor produced overall and complete response rates of 38% and 18%, respectively; the Bcl inhibitor produce overall and complete response rates of 33% and 14%, respectively; histone deacetylase inhibitors produce overall response rates of 35%-71%; and checkpoint inhibitors produce overall response rates of 40%-80% and complete response rates of 10-60%.[4] ## See also[edit] * List of hematologic conditions * large-cell lymphoma * In situ follicular lymphoma ## References[edit] 1. ^ a b c d e f g h Xerri L, Dirnhofer S, Quintanilla-Martinez L, Sander B, Chan JK, Campo E, et al. (February 2016). "The heterogeneity of follicular lymphomas: from early development to transformation". Virchows Archiv. 468 (2): 127–39. doi:10.1007/s00428-015-1864-y. PMID 26481245. 2. ^ "follicular lymphoma" at Dorland's Medical Dictionary 3. ^ Large-Cell+Lymphoma,+Follicular at the US National Library of Medicine Medical Subject Headings (MeSH) 4. ^ a b c d e f g h i j k l m n o p Dada R (June 2019). "Diagnosis and management of follicular lymphoma: A comprehensive review". European Journal of Haematology. 103 (3): 152–163. doi:10.1111/ejh.13271. PMID 31270855. 5. ^ a b c d e f g h i j k l Fischer T, Zing NP, Chiattone CS, Federico M, Luminari S (January 2018). "Transformed follicular lymphoma". Annals of Hematology. 97 (1): 17–29. doi:10.1007/s00277-017-3151-2. hdl:11380/1152780. PMID 29043381. 6. ^ a b Yoshino T, Takata K, Tanaka T, Sato Y, Tari A, Okada H (December 2018). "Recent progress in follicular lymphoma in Japan and characteristics of the duodenal type". Pathology International. 68 (12): 665–676. doi:10.1111/pin.12733. PMID 30456840. 7. ^ a b c d e f Lynch RC, Gratzinger D, Advani RH (July 2017). "Clinical Impact of the 2016 Update to the WHO Lymphoma Classification". Current Treatment Options in Oncology. 18 (7): 45. doi:10.1007/s11864-017-0483-z. PMID 28670664. 8. ^ a b c d e f g h i j k l Boughan KM, Caimi PF (May 2019). "Follicular Lymphoma: Diagnostic and Prognostic Considerations in Initial Treatment Approach". Current Oncology Reports. 21 (7): 63. doi:10.1007/s11912-019-0808-0. PMID 31119485. 9. ^ a b c d e f g Oishi N, Montes-Moreno S, Feldman AL (January 2018). "In situ neoplasia in lymph node pathology". Seminars in Diagnostic Pathology. 35 (1): 76–83. doi:10.1053/j.semdp.2017.11.001. PMID 29129357. 10. ^ a b Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (May 2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727. 11. ^ a b c d e f g h Takata K, Miyata-Takata T, Sato Y, Yoshino T (2014). "Pathology of follicular lymphoma". Journal of Clinical and Experimental Hematopathology. 54 (1): 3–9. doi:10.3960/jslrt.54.3. PMID 24942941. 12. ^ a b c d e f g Link BK (March 2018). "Transformation of follicular lymphoma - Why does it happen and can it be prevented?". Best Practice & Research. Clinical Haematology. 31 (1): 49–56. doi:10.1016/j.beha.2017.10.005. PMID 29452666. 13. ^ a b c d e f g h i j k l m n Sorigue M, Sancho JM (February 2018). "Current prognostic and predictive factors in follicular lymphoma". Annals of Hematology. 97 (2): 209–227. doi:10.1007/s00277-017-3154-z. PMID 29032510. 14. ^ EntrezGene 596 15. ^ Karube K, Scarfò L, Campo E, Ghia P (February 2014). "Monoclonal B cell lymphocytosis and "in situ" lymphoma". Seminars in Cancer Biology. 24: 3–14. doi:10.1016/j.semcancer.2013.08.003. PMID 23999128. 16. ^ EntrezGene 2146 17. ^ EntrezGene 1387 18. ^ EntrezGene 8740 19. ^ EntrezGene 8085 20. ^ Carbone A, Gloghini A (March 2014). "Emerging issues after the recognition of in situ follicular lymphoma". Leukemia & Lymphoma. 55 (3): 482–90. doi:10.3109/10428194.2013.807926. PMID 23713483. 21. ^ EntrezGene 7128 22. ^ EntrezGene 639 23. ^ EntrezGene 64121 24. ^ a b c Gascoyne RD, Nadel B, Pasqualucci L, Fitzgibbon J, Payton JE, Melnick A, et al. (December 2017). "Follicular lymphoma: State-of-the-art ICML workshop in Lugano 2015". Hematological Oncology. 35 (4): 397–407. doi:10.1002/hon.2411. PMID 28378425. 25. ^ EntrezGene 84433 26. ^ EntrezGene 974 27. ^ EntrezGene 965 28. ^ EntrezGene 1029 29. ^ EntrezGene 1030 30. ^ EntrezGene 8764 31. ^ EntrezGene 4609 32. ^ Tobin JW, Keane C, Gunawardana J, Mollee P, Birch S, Hoang T, Lee J, Li L, Huang L, Murigneux V, Fink JL, Matigian N, Vari F, Francis S, Kridel R, Weigert O, Haebe S, Jurinovic V, Klapper W, Steidl C, Sehn LH, Law S, Wykes MN, and Gandhi MK (December 2019). "Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration". J Clin Oncol. 37 (34): 3300–3309. doi:10.1200/JCO.18.02365. PMC 6881104. PMID 31461379. 33. ^ a b c d e f g h Bargetzi M, Baumann R, Cogliatti S, Dietrich PY, Duchosal M, Goede J, Hitz F, Konermann C, Lohri A, Mey U, Novak U, Papachristofilou A, Stenner F, Taverna C, Zander T, Renner C (2018). "Diagnosis and treatment of follicular lymphoma: an update". Swiss Medical Weekly. 148: w14635. doi:10.4414/smw.2018.14635. PMID 30044476. 34. ^ a b c d Takata K, Miyata-Takata T, Sato Y, Iwamuro M, Okada H, Tari A, Yoshino T (January 2018). "Gastrointestinal follicular lymphoma: Current knowledge and future challenges". Pathology International. 68 (1): 1–6. doi:10.1111/pin.12621. PMID 29292593. 35. ^ Foukas PG, de Leval L (January 2015). "Recent advances in intestinal lymphomas". Histopathology. 66 (1): 112–36. doi:10.1111/his.12596. PMID 25639480. 36. ^ Lightner AL, Shannon E, Gibbons MM, Russell MM (April 2016). "Primary Gastrointestinal Non-Hodgkin's Lymphoma of the Small and Large Intestines: a Systematic Review". Journal of Gastrointestinal Surgery. 20 (4): 827–39. doi:10.1007/s11605-015-3052-4. PMID 26676930. 37. ^ a b Pyeon SI, Song GA, Baek DH, Kim GH, Lee BE, Lee SJ, Yoon JB, Han SY, Park DY (February 2017). "Primary Follicular Lymphoma in the Rectum Incidentally Found on Screening Colonoscopy". The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. 69 (2): 139–142. doi:10.4166/kjg.2017.69.2.139. PMID 28239083. 38. ^ Marks E, Shi Y (April 2018). "Duodenal-Type Follicular Lymphoma: A Clinicopathologic Review". Archives of Pathology & Laboratory Medicine. 142 (4): 542–547. doi:10.5858/arpa.2016-0519-RS. PMID 29565210. 39. ^ Weindorf SC, Smith LB, Owens SR (November 2018). "Update on Gastrointestinal Lymphomas". Archives of Pathology & Laboratory Medicine. 142 (11): 1347–1351. doi:10.5858/arpa.2018-0275-RA. PMID 30407861. 40. ^ Moy BT, Wilmot J, Ballesteros E, Forouhar F, Vaziri H (September 2016). "Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review". Journal of Gastrointestinal Cancer. 47 (3): 255–63. doi:10.1007/s12029-016-9847-z. PMID 27277664. 41. ^ Moy BT, Wilmot J, Ballesteros E, Forouhar F, Vaziri H (September 2016). "Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review". Journal of Gastrointestinal Cancer. 47 (3): 255–63. doi:10.1007/s12029-016-9847-z. PMID 27277664. 42. ^ a b c d e Woessmann W, Quintanilla-Martinez L (June 2019). "Rare mature B-cell lymphomas in children and adolescents". Hematological Oncology. 37 Suppl 1: 53–61. doi:10.1002/hon.2585. PMID 31187530. 43. ^ a b c Koo M, Ohgami RS (May 2017). "Pediatric-type Follicular Lymphoma and Pediatric Nodal Marginal Zone Lymphoma: Recent Clinical, Morphologic, Immunophenotypic, and Genetic Insights". Advances in Anatomic Pathology. 24 (3): 128–135. doi:10.1097/PAP.0000000000000144. PMID 28277421. 44. ^ Shukla V, Lu R (August 2014). "IRF4 and IRF8: Governing the virtues of B Lymphocytes". Frontiers in Biology. 9 (4): 269–282. doi:10.1007/s11515-014-1318-y. PMC 4261187. PMID 25506356. 45. ^ "IRF8 interferon regulatory factor 8 [Homo sapiens (human)] - Gene - NCBI". 46. ^ "MAP2K1 mitogen-activated protein kinase kinase 1 [Homo sapiens (human)] - Gene - NCBI". 47. ^ a b Lones MA, Raphael M, McCarthy K, Wotherspoon A, Terrier-Lacombe MJ, Ramsay AD, Maclennan K, Cairo MS, Gerrard M, Michon J, Patte C, Pinkerton R, Sender L, Auperin A, Sposto R, Weston C, Heerema NA, Sanger WG, von Allmen D, Perkins SL (January 2012). "Primary follicular lymphoma of the testis in children and adolescents". Journal of Pediatric Hematology/Oncology. 34 (1): 68–71. doi:10.1097/MPH.0b013e31820e4636. PMC 3251817. PMID 22215099. 48. ^ Xu H, Yao F (March 2019). "Primary testicular lymphoma: A SEER analysis of 1,169 cases". Oncology Letters. 17 (3): 3113–3124. doi:10.3892/ol.2019.9953. PMC 6396186. PMID 30867741. 49. ^ Cheah CY, Wirth A, Seymour JF (January 2014). "Primary testicular lymphoma". Blood. 123 (4): 486–93. doi:10.1182/blood-2013-10-530659. PMID 24282217. 50. ^ Lossos, I. S.; Gascoyne, R. D. (2011). "Transformation of follicular lymphoma". Best Practice & Research. Clinical Haematology. 24 (2): 147–63. doi:10.1016/j.beha.2011.02.006. PMC 3112479. PMID 21658615. 51. ^ Weissmann D. "Follicular Lymphomas". University of Medicine and Dentistry of New Jersey. Retrieved 2008-07-26. 52. ^ a b c Sorigue M, Sancho JM (May 2019). "Recent landmark studies in follicular lymphoma". Blood Reviews. 35: 68–80. doi:10.1016/j.blre.2019.03.006. PMID 30928169. 53. ^ Lister A. "Follicular Lymphoma: Perspective, Treatment Options, and Strategy". MedScape. 54. ^ Solal-Céligny P, Bellei M, Marcheselli L, Pesce EA, Pileri S, McLaughlin P, Luminari S, Pro B, Montoto S, Ferreri AJ, Deconinck E, Milpied N, Gordon LI, Federico M (November 2012). "Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: results of an F2-study database". Journal of Clinical Oncology. 30 (31): 3848–53. doi:10.1200/JCO.2010.33.4474. PMID 23008294. 55. ^ Ganapathi KA, Pittaluga S, Odejide OO, Freedman AS, Jaffe ES (September 2014). "Early lymphoid lesions: conceptual, diagnostic and clinical challenges". Haematologica. 99 (9): 1421–32. doi:10.3324/haematol.2014.107938. PMC 4562530. PMID 25176983. 56. ^ Pavanello F, Steffanoni S, Ghielmini M, Zucca E (2016). "Systemic Front Line Therapy of Follicular Lymphoma: When, to Whom and How". Mediterranean Journal of Hematology and Infectious Diseases. 8 (1): e2016062. doi:10.4084/MJHID.2016.062. PMC 5111519. PMID 27872742. ## External links[edit] Classification D * ICD-10: C82 * ICD-9-CM: 202.0 * ICD-O: M9690/3 * OMIM: 151430 * MeSH: D008224 External resources * eMedicine: med/1362 * Follicular large cell lymphoma entry in the public domain NCI Dictionary of Cancer Terms * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Follicular lymphoma	c0024301	30,014	wikipedia	https://en.wikipedia.org/wiki/Follicular_lymphoma	2021-01-18T18:30:48	{"gard": ["2356"], "mesh": ["D008224"], "umls": ["C0024301"], "icd-10": ["C82"], "orphanet": ["545"], "wikidata": ["Q123251"]}
Oxyhyperglycemia is a special type of impaired glucose tolerance characterized by a rapid and transient hyperglycemia (i.e. rise in blood glucose) spike after an oral intake of glucose, the peak of this spike being high enough to cause transient, symptom free glycosuria (i.e. detectable glucose in urine), but this hyperglycemia reverses rapidly and may even go to hypoglycemia in the later phase. This sharp downstroke overshooting towards hypoglycemia distinguishes this pathologic phenomenon from the artificial hyperglycemia inducible by an intravenous bolus dose of a large amount of glucose solution. Early dumping syndrome patients usually have oxyhyperglycemia associated with any meal or OGTT. The Greek root oxy means "sharp" or "pointy".[1][2] The OGTT curve in this condition appears sharp and somewhat pointy (at least relative to the other forms of hyperglycemia)- hence this name. Dorlands dictionary defines oxyhyperglycemia as:[3] "A condition in which there is slight glycosuria and an Oral Glucose Tolerance curve that rises about 180–200 mg/dL but returns to fasting value 2.5 hrs after ingestion of the glucose." A blood level of approximately 180 mg/dL is the renal glucose threshold below which all glucose is reabsorbed from glomerular filtrate. But at blood concentrations above the renal threshold sugar starts appearing in the urine. Oxyhyperglycemia, like other forms of Impaired glucose tolerance has also been suggested to be a prediabetic condition[4] ## Contents * 1 Cause * 2 Mechanism * 3 Diagnosis * 3.1 Distinction from regular impaired glucose tolerance * 4 References ## Cause[edit] Oxyhyperglycemia is most commonly caused by early dumping syndrome, but it can rarely caused by other conditions like Graves' disease.[5] It was first described by Lawrence et al. in 1936[6][7] as often happening after gastroenterostomy. It is seen in most forms of gastrectomy, gastric bypass and gastrostomy procedures, all of which are surgical causes of dumping syndrome. ## Mechanism[edit] In early dumping syndrome, pancreatic glucagon is augmented in the early postprandial period, probably through stimulation the catecholamines involved in the generalized autonomic surge induced by the osmotic load, but at 120 min, when most of the hypoglycemias are encountered, pancreatic glucagon is no longer detectable, likely through inhibition by GLP-1.[8][9] Incretins including GLP1 and GIP also bring in the late dumping effects including the insulin rise and the reactive hypoglycemia.[10] ## Diagnosis[edit] ### Distinction from regular impaired glucose tolerance[edit] Most patients (or animals) with prediabetic type impaired glucose tolerance (serum glucose 140–200 mg/dL at 2 hours after OGTT) are generally not oxyhyperglycemic because: 1. Glycosuria is not necessary for mild impaired glucose tolerance (e.g. at approx 140–180 mg/dL range of blood glucose), is necessary for oxyhyperglycemia (i.e. peak >renal threshold). 2. In contrast to the commonly seen shallow OGTT curve, amplitude of the pointy spike in oxyhyperglycemia need not necessarily be restricted to only prediabetic range and in severe oxyhyperglycemia it may cross 250 mg/dL. In oxyhyperglycemia, by two hours, the glucose not only comes back to pre-diabetic range it may even start shooting below the fasting baseline. 3. In oxyhyperglycemia, both the upstroke (by 30 minutes) and down stroke (by 2.5 hr) happens quite fast which is unusual for other forms of prediabetes. In most cases of impaired tolerance, glucose levels usually do not come down as quickly, rather lasts for 2 hours or more. Whereas if the oxyhyperglycemia is due to an early dumping syndrome it may be followed by a late dumping syndrome which may even have a hypoglycemic state. For animal studies, occasionally oxyhyperglycemia is written as synonymous for impaired glucose tolerance[11] but mostly in the right context of gastrectomy, thus actually implying its narrower meaning than impaired glucose tolerance. ## References[edit] 1. ^ "Oxy- (sharp, pointed, keen; acidic, pungent) words: Oxymora to paroxysm, part 2 of 2". 2. ^ List of Greek and Latin roots in English 3. ^ Dorland's Illustrated Medical Dictionary E-Book Elsevier Health Sciences, 2011. https://books.google.com/books?id=mNACisYwbZoC&pg=PT6008&lpg=PT6008&dq=oxyhyperglycemia+glycosuria&source=bl&ots=aX7RNVcZk0&sig=kPMLuW1Ftdeiiz3WPuSGAT90U1w&hl=en&sa=X&ei=qeKWT7bdBcHlrAeQn5yDDg&ved=0CGEQ6AEwCA#v=onepage&q=oxyhyperglycemia%20glycosuria&f=false 4. ^ Takayoski Tobe; Mamoru Kouchi; Hiroshi Tanimura; Chiu Hsiung Huang Hyperglycemia After Gastrectomy as a Prediabetic State: Clinical Study of 100 Postgastrectomy Patients AMA Arch Surg. 1967; 94(6):836–840. http://archsurg.ama-assn.org/cgi/content/summary/94/6/836 5. ^ Nagoya J Med Sci. 1994 Mar;57(1-4):61–8. Glucose and insulin metabolism in patients with hyperthyroidism due to Graves' disease. Mano T, Kawakubo A, Yamamoto M. http://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/5712/v57n12p61_68.pdf 6. ^ Lawrence, R.D.: Symptomless Glycosurias: Differentiation by Sugar Tolerance Tests, Med Clin N Amer 31:289, 1947 7. ^ Tobe T, Kouchi M, Tanimura H, Huang C. Hyperglycemia after gastrectomy as a prediabetic stateclinical study of 100 postgastrectomy patients. Arch Surg. 1967; 94(6):836–840. 8. ^ Digestive Diseases and Sciences Volume 46, Number 9 (2001), 1915–1923, doi:10.1023/A:1010635131228 Postprandial GLP-1, Norepinephrine, and Reactive Hypoglycemia in Dumping Syndrome. B. Gebhard, J.J. Holst, C. Biegelmayer and J. Miholic. https://doi.org/10.1023%2FA%3A1010635131228 9. ^ Digestive Diseases and Sciences Volume 50, Number 12 (2005), 2263–67, doi:10.1007/s10620-005-3046-2. A Possible Role of GLP-1 in the Pathophysiology of Early Dumping Syndrome. Hiroshi Yamamoto, Tsuyoshi Mori, Hiroshi Tsuchihashi, Hiroya Akabori, Hiroyuki Naito and Tohru Tani. https://doi.org/10.1007%2Fs10620-005-3046-2 10. ^ The Journal of Clinical Endocrinology & Metabolism December 1, 2007 vol. 92 no. 12 4678–85 Patients with Neuroglycopenia after Gastric Bypass Surgery Have Exaggerated Incretin and Insulin Secretory Responses to a Mixed Meal. A. B. Goldfine, E. C. Mun, E. Devine, R. Bernier, M. Baz-Hecht, D. B. Jones, B. E. Schneider, J. J. Holst and M. E. Patti. http://jcem.endojournals.org/content/92/12/4678.full 11. ^ Journal of Endocrinology (1999) 160, 285–289 http://joe.endocrinology-journals.org/content/160/2/285.full.pdf * v * t * e Disease of the pancreas and glucose metabolism Diabetes * Types * type 1 * type 2 * gestational * MODY 1 2 3 4 5 6 * Complications * See Template:Diabetes Abnormal blood glucose levels * Hyperglycaemia * Oxyhyperglycemia * Hypoglycaemia * Whipple's triad Insulin disorders * Insulin resistance * Hyperinsulinism * Rabson–Mendenhall syndrome Other pancreatic disorders * Insulinoma * Insulitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Oxyhyperglycemia	None	30,015	wikipedia	https://en.wikipedia.org/wiki/Oxyhyperglycemia	2021-01-18T18:50:55	{"wikidata": ["Q7115981"]}
A number sign (#) is used with this entry because of evidence that susceptibility to nasopharyngeal carcinoma-3 (NPCA3) is conferred by heterozygous variation in the MST1R gene (600168) on chromosome 3p21. Description Nasopharyngeal carcinoma (NPCA) is a malignant tumor that emerges from the epithelium of the nasopharynx. It has a high incidence in southern China, and evidence suggests that there may be a genetic component that underlies familial clustering. Some patients have onset before 20 years of age (summary by Dai et al., 2016) For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to nasopharyngeal carcinoma, see NPCA1 (607107). Molecular Genetics By whole-exome sequencing of 161 cases of NPC and 895 controls from southern China, including 39 early-onset cases, 63 patients from 52 independent families, and 59 sporadic cases, Dai et al. (2016) found a significant association between variation in the MST1R gene and development of the cancer. The variants, which were confirmed by Sanger sequencing, were filtered against the 1000 Genomes Project and Exome Sequencing Project databases. Eleven variants, including 1 frameshift and 10 missense variants located at conserved residues, were found in 13 (8.7%) patients, including 2 sibs. Seven of the 13 patients had early onset, before 20 years of age: 5 heterozygous missense variants were observed in 17.9% of the early-onset cases and in only 1.2% of controls (p = 7.94 x 10(-12)). The variants identified in the early-onset cases were A973T, E705K, V670G, A327T, and R306H (600168.0001). Functional studies of the variants were not performed. However, copy number alterations of 3p21.2 (loss of heterozygosity) were found in 9 (64%) of 14 tumors derived from individuals with germline MST1R variants. In addition, proximal promoter hypermethylation resulting in downregulation of full-length MST1R was also frequently observed. Overall, the findings suggested that variation in expression of the MST1R gene, including germline variation, may predispose to the development of nasopharyngeal carcinoma. No somatic MST1R mutations were found in over 100 NPC tumors. INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Nasopharyngeal carcinoma, susceptibility to NEOPLASIA \- Nasopharyngeal carcinoma, susceptibility to MISCELLANEOUS \- Increased frequency in southern China \- Some patients may have onset before age 20 years MOLECULAR BASIS \- Susceptibility conferred by variation in the macrophage stimulating 1 receptor gene (MST1R, 600168.0001 ) ▲ 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	NASOPHARYNGEAL CARCINOMA, SUSCEPTIBILITY TO, 3	c0238301	30,016	omim	https://www.omim.org/entry/617075	2019-09-22T15:46:57	{"mesh": ["D009303"], "omim": ["617075"], "orphanet": ["150"]}
3-Hydroxyisobutyric aciduria is a rare metabolic condition in which the body is unable to breakdown certain amino acids (the building blocks of protein). This leads to a toxic buildup of particular acids known as organic acids in the blood (organic acidemia), tissues and urine (organic aciduria). Signs and symptoms of 3-hydroxyisobutyric aciduria include developmental delay, characteristic facial features and brain abnormalities. The exact underlying cause is not well understood; however, researchers believe some cases are caused by changes (mutations) in the ALDH6A1 gene and inherited in an autosomal recessive manner. Because it is so rare, there is limited evidence to support the effectiveness of treatment, but a protein-restricted diet and carnitine supplementation have been tried with varying degrees of success. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	3-Hydroxyisobutyric aciduria	c0342737	30,017	gard	https://rarediseases.info.nih.gov/diseases/5662/3-hydroxyisobutyric-aciduria	2021-01-18T18:02:25	{"mesh": ["C535312"], "omim": ["236795"], "orphanet": ["939"], "synonyms": ["Disorder of valine metabolism"]}
A rare ectodermal dysplasia syndrome characterized by a variably severe clinical picture comprising dry, thin skin, onychodysplasia, trichodysplasia, and dental abnormalities (such as hypodontia, microdontia, and persistence of deciduous teeth). 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	Dermoodontodysplasia	c1852144	30,018	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1660	2021-01-23T18:44:35	{"gard": ["1816"], "mesh": ["C565103"], "omim": ["125640"], "umls": ["C1852144"], "icd-10": ["Q82.4"]}
A number sign (#) is used with this entry because autosomal dominant mental retardation-24 (MRD24) is caused by heterozygous mutation in the DEAF1 gene (602635) on chromosome 11p15. Clinical Features Vulto-van Silfhout et al. (2014) reported 4 unrelated children with MRD24, including 2 patients previously identified by Vissers et al. (2010) and Rauch et al. (2012). All patients had delayed psychomotor development with absent or very poor expressive speech and gait abnormalities. Three had poor eye contact. Dysmorphic features were mild, but included thin and/or fair hair, straight eyebrows, full nasal tip, tented upper lip, full lower lip, and prominent chin. Three patients had skin syndactyly of toes 2-3, 2 had a sacral dimple, and 2 had hyperlaxity. All also had recurrent infections and a high pain threshold. The patients were described as having a happy disposition, but 3 had severe behavioral abnormalities consisting of autistic, compulsive, hyperactive, and aggressive behavior with striking mood swings. Molecular Genetics In 1 of 10 patients with mental retardation, Vissers et al. (2010) identified a de novo heterozygous missense mutation in the DEAF1 gene (I228S; 602635.0001). The mutation was found by exome sequencing. In a girl with nonsyndromic intellectual disability, Rauch et al. (2012) identified a de novo heterozygous missense mutation in the DEAF1 gene (Q264P; 602635.0002). The patient was ascertained from a large cohort of 51 patients with intellectual disability who underwent exome sequencing. In 2 unrelated patients with MRD24, Vulto-van Silfhout et al. (2014) identified 2 different missense mutations in the DEAF1 gene (R224W, 602635.0003 and R254S, 602635.0004). The patients were ascertained from a cohort of over 2,300 individuals with intellectual disability who underwent targeted resequencing of the DEAF1 gene. In vitro functional expression assays using a luciferase reporter indicated that all 4 of the mutations, including those reported by Vissers et al. (2010) and Rauch et al. (2012), resulted in a loss of the ability of DEAF1 to repress its own promoter, and all mutations produced proteins with loss of or significantly reduced DNA binding. Three of the mutations caused a loss of transcriptional activity. Compared to the other mutations, the R254S mutation resulted in less severe defects and enabled some residual DEAF1 activity. Vulto-van Silfhout et al. (2014) postulated a dominant-negative effect of the mutations. One of the patients also carried a heterozygous c.1570C-T transition in the SCN2A gene (182390), resulting in an arg524-to-ter (R524X) substitution, which may have influenced the severity of the intellectual disability; however, the patient did not have a history of epilepsy. Animal Model Vulto-van Silfhout et al. (2014) found that homozygous knockout of the Deaf1 gene was lethal in mice. Transgenic mice with conditional homozygous knockdown of the Deaf1 gene in brain showed increased anxiety-related behavior in field tests as well as impaired contextual memory. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Prominent chin Eyes \- Straight eyebrows \- Poor eye contact Nose \- Full nasal tip Mouth \- Tented upper lip \- Full lower lip SKELETAL Feet \- Skin syndactyly, 2-3 SKIN, NAILS, & HAIR Skin \- Sacral dimple (2 patients) NEUROLOGIC Central Nervous System \- Developmental delay \- Mental retardation, moderate to severe \- Gait abnormalities \- High pain threshold \- Lack of expressive speech \- Very poor expressive speech Behavioral Psychiatric Manifestations \- Happy disposition \- Autistic features \- Mood swings \- Aggressive behavior \- Compulsive behavior IMMUNOLOGY \- Recurrent infections MISCELLANEOUS \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the deformed epidermal autoregulatory factor 1 homolog gene (DEAF1, 602635.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL DOMINANT 24	c4014414	30,019	omim	https://www.omim.org/entry/615828	2019-09-22T15:50:57	{"doid": ["0070054"], "omim": ["615828"], "orphanet": ["178469"], "synonyms": []}
## Clinical Features Richieri-Costa and Guion-Almeida (1993) reported 2 unrelated girls with an MCA/MR syndrome of clinical anophthalmia, abnormal nares, central nervous system anomalies, and mental retardation. They referred to the condition as cerebrooculonasal syndrome. Guion-Almeida et al. (2000) reported 2 additional cases, one with and one without structural anomalies of the central nervous system and clinical anophthalmia, and both with abnormal nares. The first case reported by Guion-Almeida et al. (2000) was a female with brachycephaly, a large forehead with a depression in the midline, ocular hypertelorism, telecanthus, epicanthic folds, downslanting palpebral fissures, medial abnormally placed eyebrows, and sparse eyelashes. The nose was abnormally modeled with a proboscis-like appearance and, on the right, a small and atypical appendage-like structure. She also had malar hypoplasia, a large philtrum, a high-arched and narrow palate, and posteriorly rotated ears with a hypoplastic tragus and large conchae. Development was very mildly delayed. The second case was a male with normal growth but macrobrachycephaly, a large forehead with midline capillary hemangioma, flat supraorbital ridges, ocular hypertelorism, epicanthic folds, downslanting palpebral fissures, sparse and medially absent eyebrows, sparse eyelashes, and bilateral clinical anophthalmia. The nose was abnormally shaped and proboscis-like with marked hypoplasia of the left nostril. He also had malar hypoplasia, an atypical cleft lip, a high-arched palate, bilateral pedunculated postaxial polydactyly, genital hypoplasia, and delayed neuropsychologic development. At age 2 years he was unable to walk alone and spoke few words. Both patients showed a single maxillary central incisor. Guion-Almeida et al. (2007) reported on 13 new patients with cerebrooculonasal syndrome and reviewed 7 previously described cases. The female to male sex ratio was 12:8. All cases occurred sporadically, and no consanguinity was present. No chromosomal abnormalities were found. The authors found marked clinical variability among the patients, but noted that the nasal configuration appeared to be unique and diagnostic. They identified a mutation, a V908G change in the PTCH gene (601309.0015), in only 1 of their patients (patient 7). Ribeiro et al. (2006) had identified the same mutation in the same patient, whom they had diagnosed with holoprosencephaly-7 (HPE7; 610828). Kokitsu-Nakata et al. (2009) described the cerebrooculonasal syndrome in the first child of nonconsanguineous parents. He had brachycephaly, wide forehead, bilateral frontal encephalocele, malar hypoplasia, hypertelorism, bilateral anophthalmia, bilateral proboscis-like nares, cleft lip, abnormal palate, abnormal left auricular lobule, and cryptorchidism. Inheritance Guion-Almeida et al. (2000) suggested autosomal dominant inheritance for cerebrooculonasal syndrome because all reported cases have been sporadic and there is some evidence for advanced paternal age effect. Nomenclature See 309800 for discussion of the misuse of the term 'anophthalmia' in the medical literature. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Macrocephaly \- Brachycephaly Face \- Prominent forehead \- Flat supraorbital ridge \- Wide philtrum \- Malar hypoplasia Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Anophthalmia \- Sparse eyebrows \- Sparse eyelashes \- Hypertelorism \- Epicanthal folds Nose \- Anteverted nostrils \- Midline nasal appendage \- Elevated nasal bridge \- Short nose \- Proboscis-like nares Mouth \- Downturned mouth \- Cleft palate \- Carp-like mouth \- High-arched palate \- Narrow palate Teeth \- Single maxillary central incisor GENITOURINARY External Genitalia (Male) \- Hypoplastic genitalia SKELETAL Skull \- Craniosynostosis \- Asymmetric cranial vault Hands \- Postaxial polydactyly SKIN, NAILS, & HAIR Hair \- Sparse eyebrows \- Sparse eyelashes NEUROLOGIC Central Nervous System \- Hydrocephalus \- Mental retardation \- Encephalocele \- Hypoplastic cerebellar vermis \- Hypoplastic corpus callosum ▲ 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	CEREBROOCULONASAL SYNDROME	c1854108	30,020	omim	https://www.omim.org/entry/605627	2019-09-22T16:11:10	{"mesh": ["C565313"], "omim": ["605627"], "orphanet": ["66625"]}
Distributive shock Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body's tissues and organs.[1][2] It is one of four categories of shock, a condition where there is not enough oxygen-carrying blood to meet the metabolic needs of the cells which make up the body's tissues and organs.[2] Distributive shock is different from the other three categories of shock in that it occurs even though the output of the heart is at or above a normal level.[2] The most common cause is sepsis leading to a type of distributive shock called septic shock, a condition that can be fatal.[1] ## Contents * 1 Types * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 Research directions * 8 References * 9 External links ## Types[edit] Elbers and Ince have identified five classes of abnormal microcirculatory flow in distributive shock using side stream dark field microscopy. * Class I: all capillaries are stagnant when there is normal or sluggish venular flow. * Class II: there are empty capillaries next to capillaries that have flowing red blood cells. * Class III: there are stagnant capillaries next to capillaries with normal blood flow. * Class IV: hyperdynamic flow in capillaries adjacent to capillaries that are stagnant. * Class V: widespread hyperdynamic flow in the microcirculatory system.[2] According to the cause, there are 4 types of distributive shock: * Neurogenic shock: Decreased sympathetic stimulation leading to decreased vasal tone. * Anaphylactic shock * Septic shock * Shock due to adrenal crisis ## Causes[edit] In addition to sepsis, distributive shock can be caused by systemic inflammatory response syndrome (SIRS) due to conditions other than infection such as pancreatitis, burns or trauma.[3] Other causes include, toxic shock syndrome (TSS), anaphylaxis (a sudden, severe allergic reaction), adrenal insufficiency, reactions to drugs or toxins, heavy metal poisoning, hepatic (liver) insufficiency and damage to the central nervous system.[3] Causes of adrenal insufficiency leading to distributive shock include acute worsening of chronic adrenal insufficiency, destruction or removal of the adrenal glands, suppression of adrenal gland function due to exogenous steroids, hypopituitarism and metabolic failure of hormone production.[3] ## Pathophysiology[edit] The cause of inadequate tissue perfusion (blood delivery to tissues) in distributive shock is a lack of normal responsiveness of blood vessels to vasoconstrictive agents and direct vasodilation.[4] There are four types of distributive shock. The most common, septic shock, is caused by an infection, most frequently by bacteria, but viruses, fungi and parasites have been implicated.[3] Infection sites most likely to lead to septic shock are chest, abdomen and genitourinary tract.[3] In septic shock the blood flow in the microvasculature is abnormal with some capillaries underperfused and others with normal to high blood flow.[5] The endothelial cells lining the blood vessels become less responsive to vasocontrictive agents, lose their glycocalyx (normal coating) and negative ionic charge, become leaky and cause extensive over-expression of nitric oxide.[2] The coagulation cascade is also disrupted.[4] Tissue factor that initiates the clotting cascade is produced by activated monocytes and the endothelial cells lining the blood vessels while antithrombin and fibrinolysis are impaired.[4] Disseminated intravascular coagulation (DIC) can result from the thrombin produced in the inflammatory response.[4] The ability of red blood cells to change shape decreases and their tendency to clump together increases, inhibiting their flow through the microvasculature.[5] In anaphylactic shock low blood pressure is related to decreased systemic vascular resistance (SVR) triggered primarily by a massive release of histamine by mast cells activated by antigen-bound immunoglobulin E and also by increased production and release of prostaglandins.[4] Neurogenic shock is caused by the loss of vascular tone normally supported by the sympathetic nervous system due to injury to the central nervous system especially spinal cord injury.[4][6] Rupture of a hollow organ, with subsequent evacuation of contents in the peritoneal cavity could also determine neurogenic shock, a subtype of distributive shock. This happens due to the widespread peritoneal irritation by the ruptured viscus contents, as in peptic ulcer perforation, with consequent strong vagal activation, and generalized, extensive peripheral vasodilation and bradycardia.[7][8] Thus, in neurogenic shock, there is decreased systemic vascular resistance, CVP is typically decreased, CO decreased or normal, and PAOP decreased.[2] Distributive shock associated with adrenal crisis results from inadequate steroid hormones. ## Diagnosis[edit] This section is empty. You can help by adding to it. (February 2019) ## Treatment[edit] The main goals of treatment in distributive shock are to reverse the underlying cause and achieve hemodynamic stabilization.[9] Immediate treatment involves fluid resuscitation and the use of vasoactive drugs, both vasopressors and inotropes.[10] Hydrocortisone is used for people whose hypotension does not respond to fluid resuscitation and vasopressors.[11] Opening and keeping open the microcirculation is a consideration in the treatment of distributive shock, as a result limiting the use of vasopressors has been suggested.[2] Control of inflammation, vascular function and coagulation to correct pathological differences in blood flow and microvascular shunting has been pointed to as a potentially important adjunct goal in the treatment of distributive shock.[2] People with septic shock are treated with antimicrobial drugs to treat the causative infection.[12] Some sources of infection require surgical intervention including necrotizing fasciitis, cholangitis, abscess, intestinal ischemia, or infected medical devices.[13] Anaphylactic shock is treated with epinephrine.[14] The use of vasopressin together with norepinephrine rather than norepinephrine alone appears to decrease the risk of atrial fibrillation but with few other benefits.[15] ## Prognosis[edit] Septic shock is associated with significant mortality and is the leading non cardiac cause of death in intensive care units (ICUs).[1] ## Research directions[edit] The choice of fluids for resuscitation remains an area of research, the Surviving Sepsis Campaign an international consortium of experts, did not find adequate evidence to support the superiority crystalloid fluids versus colloid fluids.[10] Drugs such as, pyridoxalated hemoglobin polyoxyethylene, which scavenge nitric oxide from the blood have been investigated.[16] As well as methylene blue which may inhibit the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway which has been suggested to play a significant role in distributive shock.[17] ## References[edit] 1. ^ a b c Kanaparthi, Lalit K.; Klaus-Dieter, Lessnau; Peralta, Ruben (12 February 2013), Pinsky, Michael R. (ed.), "Distributive Shock: Overview: Background", Medscape Reference, Medscape, retrieved 2014-04-28. 2. ^ a b c d e f g h Elbers, Paul W.G.; Ince, Can (19 July 2006). "Mechanisms of critical illness--classifying microcirculatory flow abnormalities in distributive shock". Critical Care. 10 (4): 221. doi:10.1186/cc4969. PMC 1750971. PMID 16879732. 3. ^ a b c d e Kanaparthi et al. 2013, Overview: Etiology. 4. ^ a b c d e f Kanaparthi et al. 2013, Overview: Pathophysiology. 5. ^ a b Ince, Can (25 August 2005). "The microcirculation is the motor of sepsis". Critical Care. 4 (Supp 4): S13-9. doi:10.1186/cc3753. PMC 3226164. PMID 16168069. 6. ^ Weaver, Lynne C.; Fleming, Jennifer C.; Mathias, Christopher J.; Krassioukov, Andrie V. (2012). "Ch. 13: Disordered Cardiovascular Control After Spinal Cord Injury". In Verhaagen, Joost; McDonald, John W. (eds.). Spinal Cord Injury. Handbook of Clinical Neurology. 109. pp. 213–33. doi:10.1016/B978-0-444-52137-8.00013-9. ISBN 9780444521378. PMID 23098715. 7. ^ De-Giorgio F, Lodise M, Pascali VL, Spagnolo AG, d'Aloja E, Arena V (2015). "An Unusual Case Showing Fatal Rupture of a Gastric Ulcer or Gastromalacia? The Importance/Role of Histology for Differential Diagnosis". J Forensic Sci. 60 (1): 240–2. doi:10.1111/1556-4029.12665. PMID 25388056.CS1 maint: multiple names: authors list (link) 8. ^ Civetta, Taylor, & Kirby's Critical Care, 4th Edition. Chapter 59 Neurogenic Shock. Lippincott Williams & Wilkins 2009 9. ^ Kanaparthi et al. 2013, Treatment: Approach Considerations. 10. ^ a b Kanaparthi et al. 2013, Treatment: Resuscitation. 11. ^ Kanaparthi et al. 2013, Treatment: Corticosteroids. 12. ^ Kanaparthi et al. 2013, Treatment: Antimicrobial Treatment. 13. ^ Kanaparthi et al. 2013, Treatment: Surgical Control of Shock Sources. 14. ^ Kanaparthi et al. 2013, Treatment: Treatment of Anaphylaxis. 15. ^ McIntyre, WF; Um, KJ; Alhazzani, W; Lengyel, AP; Hajjar, L; Gordon, AC; Lamontagne, F; Healey, JS; Whitlock, RP; Belley-Côté, EP (8 May 2018). "Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis". JAMA. 319 (18): 1889–1900. doi:10.1001/jama.2018.4528. PMC 6583502. PMID 29801010. 16. ^ Kinasewitz, Gary T.; Privalle, Christopher T.; Imm, Amy; Steingrub, Jay S.; et al. (July 2008). "Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock". Critical Care Medicine. 36 (7): 1999–2007. doi:10.1097/CCM.0b013e31817bfe84. PMID 18552688. 17. ^ Jang, D.H.; Nelson, L.S.; Hoffman, R.S. (September 2013). "Methylene blue for distributive shock: A potential new use of an old antidote". Journal of Medical Toxicology. 9 (3): 242–9. doi:10.1007/s13181-013-0298-7. PMC 3770994. PMID 23580172. ## External links[edit] * Surviving Sepsis Campaign * v * t * e Shock Distributive * Septic shock * Neurogenic shock * Anaphylactic shock * Toxic shock syndrome Obstructive * Abdominal compartment syndrome Low volume * Hemorrhage * Hypovolemia * Osmotic shock Other * Spinal shock * Cryptic shock * Vasodilatory shock * v * t * e Intensive care medicine * Health science * Medicine * Medical specialities * Respiratory therapy General terms * Intensive care unit (ICU) * Neonatal intensive care unit (NICU) * Pediatric intensive care unit (PICU) * Coronary care unit (CCU) * Critical illness insurance Conditions Organ system failure Shock sequence SIRS Sepsis Severe sepsis Septic shock Multiple organ dysfunction syndrome Other shock Cardiogenic shock Distributive shock Anaphylaxis Obstructive shock Neurogenic shock Spinal shock Vasodilatory shock Organ failure Acute renal failure Acute respiratory distress syndrome Acute liver failure Respiratory failure Multiple organ dysfunction syndrome * Neonatal infection * Polytrauma * Coma Complications * Critical illness polyneuropathy / myopathy * Critical illness–related corticosteroid insufficiency * Decubitus ulcers * Fungemia * Stress hyperglycemia * Stress ulcer Iatrogenesis * Methicillin-resistant Staphylococcus aureus * Oxygen toxicity * Refeeding syndrome * Ventilator-associated lung injury * Ventilator-associated pneumonia * Dialytrauma Diagnosis * Arterial blood gas * Catheter * Arterial line * Central venous catheter * Pulmonary artery catheter * Blood cultures * Screening cultures Life-supporting treatments * Airway management * Chest tube * Dialysis * Enteral feeding * Goal-directed therapy * Induced coma * Mechanical ventilation * Therapeutic hypothermia * Total parenteral nutrition * Tracheal intubation Drugs * Analgesics * Antibiotics * Antithrombotics * Inotropes * Intravenous fluids * Neuromuscular-blocking drugs * Recombinant activated protein C * Sedatives * Stress ulcer prevention drugs * Vasopressors ICU scoring systems * APACHE II * Glasgow Coma Scale * PIM2 * SAPS II * SAPS III * SOFA Physiology * Hemodynamics * Hypotension * Level of consciousness * Acid–base imbalance * Water-electrolyte imbalance Organisations * Society of Critical Care Medicine * Surviving Sepsis Campaign * European Society of Paediatric and Neonatal Intensive Care Related specialties * Anesthesiology * Cardiology * Internal medicine * Neurology * Pediatrics * Pulmonology * Surgery * Traumatology * v * t * e Symptoms and signs relating to the circulatory system Chest pain * Referred pain * Angina * Levine's sign Auscultation * Heart sounds * Split S2 * S3 * S4 * Gallop rhythm * Heart murmur * Systolic * Functional murmur * Still's murmur * Diastolic * Pulmonary insufficiency * Graham Steell murmur * Continuous * Carey Coombs murmur * Mitral insufficiency * Presystolic murmur * Pericardial friction rub * Heart click * Bruit * carotid Pulse * Tachycardia * Bradycardia * Pulsus paradoxus * doubled * Pulsus bisferiens * Pulsus bigeminus * Pulsus alternans Other * Palpitations * Apex beat * Cœur en sabot * Jugular venous pressure * Cannon A waves * Hyperaemia * Shock * Cardiogenic * Obstructive * Hypovolemic * Distributive * See further Template:Shock Cardiovascular disease Aortic insufficiency * Collapsing pulse * De Musset's sign * Duroziez's sign * Müller's sign * Austin Flint murmur * Mayne's sign Other endocardium * endocarditis: Roth's spot * Janeway lesion/Osler's node * Bracht–Wachter bodies Pericardium * Cardiac tamponade/Pericardial effusion: Beck's triad * Ewart's sign Other * rheumatic fever: * Anitschkow cell * Aschoff body * EKG * J wave * Gallavardin phenomenon Vascular disease Arterial * aortic aneurysm * Cardarelli's sign * Oliver's sign * pulmonary embolism * Right heart strain * radial artery sufficiency * Allen's test * pseudohypertension * thrombus * Lines of Zahn * Adson's sign * arteriovenous fistula * Nicoladoni sign Venous * Friedreich's sign * Caput medusae * Kussmaul's sign * Trendelenburg test * superior vena cava syndrome * Pemberton's sign [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Distributive shock	c2938913	30,021	wikipedia	https://en.wikipedia.org/wiki/Distributive_shock	2021-01-18T19:00:28	{"umls": ["C2938913"], "wikidata": ["Q5283218"]}
Vibratory urticaria is a rare condition that is characterized by itching, reddish skin and swelling within minutes of local exposure to vibration. Areas of skin that are most exposed to the stimulus (often the hands) are generally more severely affected. People with this condition may also experience flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth during episodes of skin involvement. Common triggers include mowing the lawn, riding a motorcycle, horseback riding, or mountain biking. Vibratory urticaria is caused by changes (mutations) in the ADGRE2 gene and appears to be inherited in an autosomal dominant manner. Treatment involves avoiding vibration stimulus and use of antihistamines. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Vibratory urticaria	c0473546	30,022	gard	https://rarediseases.info.nih.gov/diseases/9806/vibratory-urticaria	2021-01-18T17:57:11	{"mesh": ["C536347"], "omim": ["125630"], "umls": ["C0473546"], "orphanet": ["493342"], "synonyms": ["Angioedema, vibratory", "Vibratory angioedema"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Microangiopathy" – news · newspapers · books · scholar · JSTOR (October 2013) (Learn how and when to remove this template message) This article appears to be a dictionary definition. Please rewrite it to present the subject from an encyclopedic point of view. If it cannot be turned into a full encyclopedia article in the near future, consider moving it to Wiktionary. Steps for moving to Wiktionary: 1. Check that this article meets Wiktionary's criteria for inclusion. 2. Check that Wiktionary does not have an article on this word or phrase, as verified using the search page. If Wiktionary has a definition already, change this tag to {{TWCleanup2}} or else consider a soft redirect to Wiktionary by replacing the text on this page with {{Wi}}. If Wiktionary does not have the definition yet, consider moving the whole article to Wiktionary by replacing this tag with the template {{Copy to Wiktionary}}. This template will no longer automatically categorize articles as candidates to move to Wiktionary. (Learn how and when to remove this template message) Microangiopathy Other namesMicrovascular disease, small vessel disease Microangiopathy (or microvascular disease, or small vessel disease) is an angiopathy (i.e. disease of blood vessels) affecting small blood vessels in the body.[1] It can be contrasted to macroangiopathy, or large vessel disease. Cerebral small vessel disease refers to a group of diseases that affect the small arteries, arterioles, venules, and capillaries of the brain. Age-related and hypertension-related small vessel diseases and cerebral amyloid angiopathy are the most common forms. Coronary small vessel disease is a type of coronary heart disease (CHD) that affects the arterioles and capillaries of the heart. Coronary small vessel disease is also known as microvascular angina, microvascular dysfunction, non-obstructive coronary disease, or in the past, cardiac syndrome X. ## Contents * 1 Pathophysiology * 2 Therapy * 3 References * 4 External links ## Pathophysiology[edit] One cause of microangiopathy is long-term diabetes mellitus. In this case, high blood glucose levels cause the endothelial cells lining the blood vessels to take in more glucose than normal (these cells do not depend on insulin). They then form more glycoproteins on their surface than normal, and also cause the basement membrane in the vessel wall to grow abnormally thicker and weaker. Therefore they bleed, leak protein, and slow the flow of blood through the body. As a result, some organs and tissues do not get enough blood (carrying oxygen & nutrients) and are damaged, for example, the retina (diabetic retinopathy) or kidney (diabetic nephropathy). Nerves and neurons, if not sufficiently supplied with blood, are also damaged, which leads to loss of function (diabetic neuropathy, especially peripheral neuropathy). Massive microangiopathy may cause microangiopathic hemolytic anemia (MAHA). ## Therapy[edit] See therapy of arteriosclerosis. Laser therapy of diabetic retinopathy. A number of medicines, such as calcium dobesilate, are being marketed for the specific treatment of microangiopathy. The efficacy of calcium dobesilate has been described e.g. in patients with diabetic retinopathy[2] or diabetic nephropathy.[3] ## References[edit] 1. ^ "microangiopathy" at Dorland's Medical Dictionary 2. ^ Zhang, XinYuan; Liu, Wei; Wu, ShanShan; Jin, JingLong; Li, WeiHong; Wang, NingLi (2014-12-20). "Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis". Science China Life Sciences. 58 (1): 101–107. doi:10.1007/s11427-014-4792-1. ISSN 1674-7305. PMID 25528255. 3. ^ Haller, Hermann; Ji, Linong; Stahl, Klaus; Bertram, Anna; Menne, Jan (2017). "Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition". BioMed Research International. 2017: 1909258. doi:10.1155/2017/1909258. ISSN 2314-6133. PMC 5634607. PMID 29082239. ## External links[edit] Classification D * ICD-9-CM: 443.9 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Microangiopathy	c0155765	30,023	wikipedia	https://en.wikipedia.org/wiki/Microangiopathy	2021-01-18T19:00:59	{"umls": ["C0155765"], "icd-9": ["443.9"], "wikidata": ["Q1412400"]}
Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease (PCWH) is a systemic disease characterized by the association of the features of Waardenburg-Shah syndrome (WSS) with neurological features of variable severity. ## Epidemiology Prevalence is unknown. Less than 50 cases have been reported in the literature so far. ## Clinical description PCWH occurs in the neonatal and infancy period, and includes features of WSS (sensorineural hearing loss, iris heterochromia, skin hypopigmentation associated with Hirschsprung disease) and neurological features (neonatal hypotonia, intellectual disability of variable severity, nystagmus, progressive spasticity, ataxia and epilepsy). These signs are not fully penetrant (PCWH without Hirschsprung disease is sometimes referred as PCW), the depigmentation may not be obvious, and there is a broad range of severity for the neurologic features. Autonomic dysfunction (asialia, alacrima and hypohidrosis, bradycardia and arrhythmia) may also be present. Delayed white matter myelination is observed on brain magnetic resonance imaging (MRI), and may also be responsible for neuropathy at the peripheral level. MRI often shows defects of the semi-circular canals and agenesis of the olfactory bulbs. Kallmann syndrome can be associated. ## Etiology Most of the cases are caused by mutations involving the SOX10 gene (22q13.1, coding for the SOX10 transcription factor). Most frequently truncating mutations of the last coding exon induce escape from NMD (non-sense mediated mRNA decay), although a few gene deletions and missense mutations have also been described. ## Diagnostic methods Diagnosis is suspected on recognition of the clinical picture and should be confirmed by genetic molecular analysis. ## Differential diagnosis The disease overlaps with central or peripheral neuropathies/dysmyelination, and the diagnosis may be difficult in absence of the typical Waardenburg syndrome depigmentation. ## Antenatal diagnosis Prenatal diagnosis is possible by fetal DNA mutation analysis if a causal mutation is identified in a member of the family (either in case of an affected parent (a rare situation) or due to the risk of germline mosaicism). ## Genetic counseling The inheritance pattern of PCWH is autosomal dominant (parents of an affected individual have a probability of 50% to transmit the causal mutation to the offspring). Most cases are sporadic but a few patients with an affected sibling have been reported and are associated with germinal mosaicism in one of the parents. Genetic counseling should be offered to affected families in order to provide more information about this genetic condition, its risk of recurrence and the availability of prenatal diagnosis. ## Management and treatment Management is only symptomatic, consisting in the management of WS (protection from exposure to ultraviolet light, avoidance of sunburn, management of hearing loss), Hirschprung disease (surgical treatment) and the neurologic manifestations. ## Prognosis The prognosis and disease course may be severe with onset of deafness, intellectual disability and sometimes motor impairment. In rare cases, the disease is fatal shortly after birth. Long-term evolution in adulthood is not well established. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease	c1836727	30,024	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163746	2021-01-23T18:02:30	{"mesh": ["C563789"], "omim": ["609136"], "umls": ["C1836727"], "icd-10": ["E75.2"], "synonyms": ["Neurologic Waardenburg-Shah syndrome", "PCWH", "WS4 plus"]}
Kasabach–Merritt syndrome Other namesHemangioma-thrombocytopenia syndrome SpecialtyHematology Kasabach–Merritt syndrome, also known as hemangioma with thrombocytopenia[1] is a rare disease, usually of infants, in which a vascular tumor leads to decreased platelet counts and sometimes other bleeding problems,[2] which can be life-threatening.[3] It is also known as hemangioma thrombocytopenia syndrome. It is named after Haig Haigouni Kasabach and Katharine Krom Merritt, the two pediatricians who first described the condition in 1940.[4][5] ## Contents * 1 Pathophysiology * 2 Diagnosis * 3 Management * 3.1 Supportive care * 3.2 Definitive treatment * 4 Prognosis * 5 See also * 6 References * 7 External links ## Pathophysiology[edit] Kasabach–Merritt syndrome is usually caused by a hemangioendothelioma or other vascular tumor, often present at birth.[6][7] Although these tumors are relatively common, they only rarely cause Kasabach–Merritt syndrome.[citation needed] When these tumors are large or are growing rapidly, sometimes they can trap platelets, causing severe thrombocytopenia. The combination of vascular tumor and consumptive thrombocytopenia defines Kasabach–Merritt syndrome. Tumors can be found in the trunk, upper and lower extremities, retroperitoneum, and in the cervical and facial areas.[2] This consumptive coagulopathy also uses up clotting factors, such as fibrinogen which may worsen bleeding. The coagulopathy can progress to disseminated intravascular coagulation and even death.[2] Hemolytic anemia secondary to microangiopathic destruction (physical damage) of the RBCs can be expressed as mild, moderate, or severe.[8] ## Diagnosis[edit] The diagnostic workup[8] is directed by the presenting signs and symptoms, and can involve: * blood counts, clotting studies, and other laboratory testing * imaging tests (ultrasound, CT scan, MRI, sometimes angiography, and rarely nuclear medicine scans) * Biopsy of the tumor is contraindicated due to risk of bleeding. Patients uniformly show severe thrombocytopenia, low fibrinogen levels, high fibrin degradation products (due to fibrinolysis), and microangiopathic hemolysis.[2] ## Management[edit] Management of Kasabach–Merritt syndrome, particularly in severe cases, can be complex and require the joint effort of multiple subspecialists. This is a rare disease with no consensus treatment guidelines or large randomized controlled trials to guide therapy.[citation needed] ### Supportive care[edit] Patient with Kasabach–Merritt syndrome can be extremely ill and may need intensive care. They are at risk of bleeding complications including intracranial hemorrhage. The thrombocytopenia and coagulopathy are managed with platelet transfusions and fresh frozen plasma, although caution is needed due to the risk of fluid overload and heart failure from multiple transfusions. The possibility of disseminated intravascular coagulation, a dangerous and difficult-to-manage condition, is concerning. Anticoagulant and antiplatelet medications can be used after careful assessment of the risks and benefits.[8] ### Definitive treatment[edit] Generally, treatment of the underlying vascular tumor results in resolution of Kasabach–Merritt syndrome. If complete surgical resection is feasible, it provides a good opportunity for cure (although it can be dangerous to operate on a vascular tumor in a patient prone to bleeding, even with appropriate surgical subspecialists involved).[8] If surgery is not possible, various other techniques[2] can be used to control the tumor: * embolization (by interventional radiology) can limit the tumor's blood supply * external compression bandages can have similar effects * certain medications, including: * corticosteroids * alpha-interferon * chemotherapy (e.g. vincristine) * radiation therapy has been used, often successfully, but now is avoided whenever possible due to the risk of long-term adverse effects (e.g. risk for future cancer). ## Prognosis[edit] Kasabach–Merritt syndrome has a mortality rate of about 30%.[9][10] For patients that survive the acute disease, supportive care may be required through a gradual recovery.[citation needed]Furthermore, patients may need care from a dermatologist or plastic surgeon for residual cosmetic lesions or an otolaryngologist for head & neck/airway involvement. On long-term followup, most patients have skin discoloration and/or mild disfiguration from the dormant tumor.[11] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 597. ISBN 978-0-7216-2921-6. 2. ^ a b c d e Hall G (2001). "Kasabach–Merritt syndrome: pathogenesis and management". Br J Haematol. 112 (4): 851–62. doi:10.1046/j.1365-2141.2001.02453.x. PMID 11298580. 3. ^ Shim W (1968). "Hemangiomas of infancy complicated by thrombocytopenia". Am J Surg. 116 (6): 896–906. doi:10.1016/0002-9610(68)90462-5. PMID 4881491. 4. ^ Kasabach HH, Merritt KK (1940). "Capillary hemangioma with extensive purpura: report of a case". Am J Dis Child. 59 (5): 1063. doi:10.1001/archpedi.1940.01990160135009. 5. ^ Kasabach–Merritt syndrome at Who Named It? 6. ^ Enjolras O, Wassef M, Mazoyer E, Frieden I, Rieu P, Drouet L, Taïeb A, Stalder J, Escande J (1997). "Infants with Kasabach–Merritt syndrome do not have "true" hemangiomas". J Pediatr. 130 (4): 631–40. doi:10.1016/S0022-3476(97)70249-X. hdl:2066/26075. PMID 9108863. 7. ^ el-Dessouky M, Azmy A, Raine P, Young D (1988). "Kasabach–Merritt syndrome". J Pediatr Surg. 23 (2): 109–11. doi:10.1016/S0022-3468(88)80135-0. PMID 3278084. 8. ^ a b c d Kasabach-Merritt Syndrome at eMedicine 9. ^ Larsen, EC; Zinkham, WH; Eggleston, JC; Zitelli, BJ (June 1987). "Kasabach-Merritt syndrome: therapeutic considerations". Pediatrics. 79 (6): 971–80. PMID 3108848. 10. ^ Osman, NM (2013). "Kasabach - Merritt syndrome: A case report". Sudanese Journal of Paediatrics. 13 (1): 49–52. PMC 4949964. PMID 27493358. 11. ^ Enjolras O, Mulliken J, Wassef M, Frieden I, Rieu P, Burrows P, Salhi A, Léauté-Labrèze C, Kozakewich H (2000). "Residual lesions after Kasabach–Merritt phenomenon in 41 patients". J Am Acad Dermatol. 42 (2 Pt 1): 225–35. doi:10.1016/S0190-9622(00)90130-0. PMID 10642677. ## External links[edit] Classification D * ICD-10: D69.5 (ILDS D69.507) * ICD-9-CM: 287.39 * OMIM: 141000 * MeSH: D059885 * DiseasesDB: 30701 * SNOMED CT: 86635005 External resources * eMedicine: med/1221 ped/1234 * Orphanet: 2330 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Kasabach–Merritt syndrome	c0221025	30,025	wikipedia	https://en.wikipedia.org/wiki/Kasabach%E2%80%93Merritt_syndrome	2021-01-18T18:44:03	{"gard": ["70"], "mesh": ["D059885"], "icd-9": ["287.39"], "icd-10": ["D69.5"], "orphanet": ["2330"], "wikidata": ["Q764185"]}
## Description VACTERL describes a constellation of congenital anomalies, including vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects; see 192350. Cases of familial VACTERL with hydrocephalus (H) have been reported with suggestion of autosomal recessive or X-linked inheritance (see 314390). Other patients thought to have VACTERL-H, including 2 unrelated infants reported by Porteous et al. (1992), had been found to have Fanconi anemia (see 227650). Porteous et al. (1992) suggested that chromosomal breakage studies should be performed in all cases of VACTERL/VACTERL-H to rule out Fanconi anemia. Alter et al. (2007) noted that a VATER phenotype had been reported in Fanconi anemia of complementation groups A (227650), C (227645), D1 (605724), E (600901), F (603467), and G (614082). X-linked VACTERL-H is also associated with mutations in the FANCB gene (300515). Clinical Features Sujansky and Leonard (1983) described 3 sibs with VACTERL-H. The index case had hydrocephalus, tracheoesophageal fistula, congenital heart disease, renal hypoplasia, and bilateral agenesis of radii and thumbs. She died at 4.5 months of age. The other 2 sibs had similar malformations with in utero demise. Iafolla et al. (1991) described 3 unrelated infants with hydrocephalus secondary to aqueductal stenosis in addition to the multisystemic features of the VATER association. One patient died secondary to respiratory failure, but 2 survived (30 months and 19 months) following early neurosurgical intervention. The authors cautioned against labeling the VATER and hydrocephalus association as a uniformly lethal or developmentally devastating disorder. The infants in neither of these reports had, it seems, anal atresia. Briard et al. (1984) also reported familial occurrence of the VACTERL association with hydrocephalus. Evans et al. (1989) discussed VACTERL with hydrocephalus on the basis of 8 patients who had hydrocephalus and at least 2 other anomalies compatible with the VACTERL association. Their patient 7 was born to consanguineous parents. Corsello and Giuffre (1994) described a case of VACTERL in association with hydrocephalus and occipital encephalocele. Cleft palate and severe upper limb reduction defects were present in this male child of first-cousin parents. Molecular Genetics ### Associations Pending Confirmation Reardon et al. (2001) reported a heterozygous de novo his61-to-asp (H61D) mutation in the PTEN gene (see 601728.0030) in a child with features of VATER association with hydrocephalus, including macrocephaly, ventriculomegaly, tracheoesophageal fistula, and bilateral radial hand anomalies. Reardon et al. (2001) acknowledged that the child did not represent a classic example of the phenotype. They also emphasized the heterogeneity of this phenotype and discussed possible etiologic mechanisms. Skel \- Vertebral anomalies \- Anal atresia GU \- Renal hypoplasia Neuro \- Hydrocephalus \- Aqueductal stenosis Inheritance \- ? Autosomal recessive Cardiac \- Congenital heart defect Resp \- Respiratory failure Misc \- Stillbirth/neonatal death Limbs \- Radial dysplasia \- Absent thumbs GI \- T-E fistula \- No anal atresia ▲ 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	VACTERL ASSOCIATION WITH HYDROCEPHALUS	c1848599	30,026	omim	https://www.omim.org/entry/276950	2019-09-22T16:21:25	{"doid": ["14679"], "mesh": ["C564751"], "omim": ["276950"], "orphanet": ["3412"], "synonyms": ["Alternative titles", "Sujansky-Leonard syndrome", "VACTERL-H"]}
Cancer arises in the head or neck region Head and neck cancer Extensive cancer of the tongue with surrounding lichen planus SpecialtyOncology, oral and maxillofacial surgery SymptomsLump or sore that does not heal, sore throat that does not go away, trouble swallowing, change in the voice[1] Risk factorsAlcohol, tobacco, betel quid, human papillomavirus, radiation exposure, certain workplace exposures, Epstein-Barr virus[1][2] Diagnostic methodTissue biopsy[1] PreventionNot using tobacco or alcohol[2] TreatmentSurgery, radiation therapy, chemotherapy, targeted therapy[1] Frequency5.5 million (affected during 2015)[3] Deaths379,000 (2015)[4] Head and neck cancer develops from tissues in the mouth, larynx (throat), salivary glands, nose, sinuses or the skin of the face. Symptoms predominantly include a sore that does not heal or a change in the voice.[1] Some may experience a sore throat that does not go away. In those with advanced disease, there may be unusual bleeding, facial pain, numbness or swelling, and visible lumps on the outside of the neck or oral cavity. Given the location of these cancers, trouble breathing may also be present.[5] The majority of head and neck cancer is caused by the use of alcohol or tobacco, including smokeless tobacco, with increasing cases linked to the human papillomavirus (HPV).[5][2] Other risk factors include Epstein-Barr virus, betel quid, radiation exposure, certain workplace exposures.[5] About 90% are pathologically classified as squamous cell cancers.[6][2] The diagnosis is confirmed by tissue biopsy.[5] The degree of surrounding tissue invasion and distant spread may be determined by medical imaging and blood tests.[5] Not using tobacco or alcohol can reduce the risk for head and neck cancer.[2] The HPV vaccine may reduce the lifetime risk of oral cancer if taken prior to the onset of sexual activity, but confirmation will likely not be known until around 2060.[7] This is because oropharyngeal cancer typical presents in the 4th - 6th decade of life, and this is a relatively new vaccine. While screening in the general population does not appear to be useful, screening high risk groups by examination of the throat might be useful.[2] Head and neck cancer often is curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late.[2] Treatment may include a combination of surgery, radiation therapy, chemotherapy, and targeted therapy.[5] Previous diagnosis and treatment of one head and neck cancer confers higher risk of developing a second head and neck cancer or recurrence.[5] Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide with 890,000 new cases documented and 450,000 dying from the disease.[7] In the United States, head and neck cancer makes up 3% of all cancer cases (averaging 53,000 new diagnoses per year) and 1.5% of cancer deaths [8] Notably, head and neck cancer secondary to chronic alcohol or tobacco use has been steadily declining as less of the population chronically smokes tobacco.[7] However, HPV-associated oropharyngeal cancer is rising, particularly in younger people in westernized nations, which is thought to be reflective of changes in oral sexual practices.[7] The usual age at diagnosis is between 55 and 65 years old.[9] The average 5-year survival following diagnosis in the developed world is 42-64%.[9][10] ## Contents * 1 Signs and symptoms * 1.1 Mouth * 1.2 Nose * 1.3 Nasopharynx * 1.4 Throat * 1.5 Hypopharynx * 1.6 Larynx * 1.7 Trachea * 2 Causes * 2.1 Alcohol and tobacco * 2.2 Diet * 2.3 Betel nut * 2.4 Infection * 2.4.1 Human papillomavirus * 2.4.2 Epstein–Barr virus * 2.5 Gastroesophageal reflux disease * 2.6 Hematopoietic stem cell transplantation * 2.7 Other possible causes * 3 Diagnosis * 3.1 Histopathology * 3.1.1 Squamous-cell carcinoma * 3.1.2 Adenocarcinoma * 4 Prevention * 5 Management * 5.1 Surgery * 5.2 Radiation therapy * 5.3 Chemotherapy * 5.4 Photodynamic therapy * 5.5 Targeted therapy * 5.6 Immunotherapy * 5.7 Treatment side effects * 5.8 Psychosocial * 6 Prognosis * 6.1 Problem of second primaries * 6.2 Digestive system * 6.3 Respiratory system * 6.4 Mental health * 6.4.1 Patient Experience * 6.5 Others * 7 Epidemiology * 8 Research * 9 References * 10 External links ## Signs and symptoms[edit] Symptoms predominantly include a sore of the face or oral cavity that does not heal, trouble swallowing, or a change in the voice. In those with advanced disease, there may be unusual bleeding, facial pain, numbness or swelling, and visible lumps on the outside of the neck or oral cavity.[11] Head and neck cancer often begins with benign signs and symptoms of disease, like an enlarged lymph node on the outside of the neck, a hoarse-sounding voice or progressive worsening cough or sore throat. In the case of head and neck cancer, these symptoms will be notably persistent and become chronic. There may be a lump or a sore in the throat or neck that does not heal or go away. There may be difficult or painful swallowing. Speaking may become difficult. There may also be a persistent earache.[12] Other symptoms can include: a lump in the lip, mouth or gums, ulcers or mouth sores that do not heal, bleeding from the mouth or numbness, bad breath, discolored patches that persist in the mouth, a sore tongue, and slurring of speech if the cancer is affecting the tongue. There may also be congested sinuses, weight loss, and some numbness or paralysis of facial muscles. ### Mouth[edit] Main article: Oral cancer Squamous cell carcinoma of the mouth. Squamous cell cancers are common in areas of the mouth, including the inner lip, tongue, floor of mouth, gums, and hard palate. Cancers of the mouth are strongly associated with tobacco use, especially use of chewing tobacco or dipping tobacco, as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with surgery than are other head and neck cancers. Surgeries for oral cancers include: * Maxillectomy (can be done with or without orbital exenteration) * Mandibulectomy (removal of the lower jaw or part of it) * Glossectomy (tongue removal, can be total, hemi or partial) * Radical neck dissection * Combinational e.g., glossectomy and laryngectomy done together. The defect is typically covered/improved by using another part of the body and/or skin grafts and/or wearing a prosthesis. ### Nose[edit] Main article: Paranasal sinus and nasal cavity cancer Paranasal sinus and nasal cavity cancer affects the nasal cavity and the paranasal sinuses. Most of these cancers are squamous cell carcinomas.[13] ### Nasopharynx[edit] Main article: Nasopharynx cancer Nasopharyngeal cancer arises in the nasopharynx, the region in which the nasal cavities and the Eustachian tubes connect with the upper part of the throat. While some nasopharyngeal cancers are biologically similar to the common head and neck squamous cell carcinomas (HNSCCs), "poorly differentiated" nasopharyngeal carcinoma is lymphoepithelioma, which is distinct in its epidemiology, biology, clinical behavior, and treatment, and is treated as a separate disease by many experts. ### Throat[edit] Main articles: Oropharyngeal cancer and HPV-positive oropharyngeal cancer Most oropharyngeal cancers are squamous cell carcinomas that begin in the oropharynx (throat), the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils.[1] Squamous cell cancers of the tonsils are more strongly associated with human papillomavirus infection than are cancers of other regions of the head and neck. HPV-positive oropharyngeal cancer generally has a better outcomes than HPV-negative disease with a 54% better survival,[14] but this advantage for HPV associated cancer applies only to oropharyngeal cancers.[15] People with oropharyngeal carcinomas are at high risk of developing second primary head and neck cancer.[16] ### Hypopharynx[edit] Main article: Hypopharyngeal cancer The hypopharynx includes the pyriform sinuses, the posterior pharyngeal wall, and the postcricoid area. Tumors of the hypopharynx frequently have an advanced stage at diagnosis, and have the most adverse prognoses of pharyngeal tumors. They tend to metastasize early due to the extensive lymphatic network around the larynx. ### Larynx[edit] Main article: Laryngeal cancer Laryngeal cancer begins in the larynx or "voice box." Cancer may occur on the vocal folds themselves ("glottic" cancer), or on tissues above and below the true cords ("supraglottic" and "subglottic" cancers respectively). Laryngeal cancer is strongly associated with tobacco smoking. Surgery can include laser excision of small vocal cord lesions, partial laryngectomy (removal of part of the larynx) or total laryngectomy (removal of the whole larynx). If the whole larynx has been removed, the person is left with a permanent tracheostomy. Voice rehabilitation in such patients can be achieved through three important ways - esophageal speech, tracheoesophageal puncture, or electrolarynx. One would likely require the help of intensive teaching and speech therapy and/or an electronic device. ### Trachea[edit] Cancer of the trachea is a rare cancer usually classed as a lung cancer.[17] Most tumors of the salivary glands differ from the common squamous cell carcinomas of the head and neck in cause, histopathology, clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include teratomas, adenocarcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas.[18] Rarer still are melanomas and lymphomas of the upper aerodigestive tract. ## Causes[edit] ### Alcohol and tobacco[edit] Main articles: Tobacco smoking and Alcohol (drug) When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Around 75% of cases are caused by alcohol and tobacco use.[1] Tobacco smoking is one of the main risk factors for head and neck cancer. A major carcinogenic compound in tobacco smoke is acrylonitrile.[19] Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA.[20] (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic.[21][22] DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG[23] and removes formamidopyrimidines from DNA.[24] However, cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.[25] The ex-smoker's risk for developing a head and neck cancer begins to approach the risk in the general population 15 years after smoking cessation.[26] The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention. Smokeless tobacco is a cause of oral cancer and oropharyngeal cancer.[27] Cigar smoking is also an important risk factor for oral cancer.[28] Other environmental carcinogens suspected of being potential causes of head and neck cancer include occupational exposures such as nickel ore refining, exposure to textile fibers, and woodworking. Use of marijuana, especially when younger, has been linked to an increase in squamous-cell carcinoma cases in at least one study,[29] while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma.[30][31] ### Diet[edit] Excessive consumption of eggs, processed meats, and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.[32] Vitamin E was not found to prevent the development of leukoplakia, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers.[33] Another study examined a combination of Vitamin E and beta carotene in smokers with early-stage cancer of the oropharynx, and found a worse prognosis in the vitamin users.[34] ### Betel nut[edit] Betel nut chewing is associated with an increased risk of squamous cell cancer of the head and neck.[1][35] ### Infection[edit] #### Human papillomavirus[edit] Some head and neck cancers are caused by human papillomavirus (HPV).[1] In particular, HPV16 is a causal factor for some head and neck squamous-cell carcinomas (HNSCCs).[36][37] Approximately 15-25% of HNSCC contain genomic DNA from HPV,[38] and the association varies based on the site of the tumor,[39] especially HPV-positive oropharyngeal cancer, with highest distribution in the tonsils, where HPV DNA is found in (45 to 67%) of the cases,[40] less often in the hypopharynx (13%–25%), and least often in the oral cavity (12%–18%) and larynx (3%–7%).[41][42] Some experts estimate that while up to 50% of cancers of the tonsil may be infected with HPV, only 50% of these are likely to be caused by HPV (as opposed to the usual tobacco and alcohol causes). The role of HPV in the remaining 25-30% is not yet clear.[43] Oral sex is not risk free and results in a significant proportion of HPV-related head and neck cancer.[44] Positive HPV16 status is associated with improved prognosis over HPV-negative OSCC.[45] HPV can induce tumor by several mechanisms:[46] 1. E6 and E7 oncogenic proteins. 2. Disruption of tumor suppressor genes. 3. High-level DNA amplifications, for example, oncogenes. 4. Generating alternative nonfunctional transcripts . 5. interchromosomal rearrangements. 6. Distinct host genome methylation and expression patterns, produced even when virus isn't integrated into the host genome. Induction of cancer can be associated for the expression of viral oncoproteins, the most important E6 and E7, or other mechanisms many of them run by the integration such as the generation of altered transcripts, disruption of tumor suppressors, high levels of DNA amplifications, interchromosomial rearrangements, or changes in DNA methylation patterns, the latter being able to find even when the virus is identified in episomes.[47][39] E6 sequesters p53 to promote p53 degradation while pRb inhibits E7. p53 prevents cell growth when DNA is damaged by activating apoptosis and p21, a kinase that blocks the formation of cyclin D / Cdk4 avoiding pRb phosphorylation and thereby prevents release of E2F is a transcription factor required for activation of genes involved in cell proliferation. pRb remains bound to E2F while this action phosphorylated preventing activation of proliferation. Therefore, E6 and E7 act synergistically in triggering cell cycle progression and therefore uncontrolled proliferation by inactivating the p53 and Rb tumor suppressors.[48] Viral integration tends to occur in or near oncogenes or tumor suppressor genes and it is for this reason that the integration of the virus can greatly contribute to the development of tumor characteristics.[47] #### Epstein–Barr virus[edit] Epstein–Barr virus (EBV) infection is associated with nasopharyngeal cancer. Nasopharyngeal cancer occurs endemically in some countries of the Mediterranean and Asia, where EBV antibody titers can be measured to screen high-risk populations. Nasopharyngeal cancer has also been associated with consumption of salted fish, which may contain high levels of nitrites.[49] ### Gastroesophageal reflux disease[edit] The presence of acid reflux disease (gastroesophageal reflux disease [GERD]) or larynx reflux disease can also be a major factor. Stomach acids that flow up through the esophagus can damage its lining and raise susceptibility to throat cancer. ### Hematopoietic stem cell transplantation[edit] Patients after hematopoietic stem cell transplantation (HSCT) are at a higher risk for oral squamous cell carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.[50] This effect is supposed to be owing to the continuous lifelong immune suppression and chronic oral graft-versus-host disease.[50] ### Other possible causes[edit] There are several risk factors for developing throat cancer. These include smoking or chewing tobacco or other things, such as gutkha, or paan, heavy alcohol consumption, poor diet resulting in vitamin deficiencies (worse if this is caused by heavy alcohol intake), weakened immune system, asbestos exposure, prolonged exposure to wood dust or paint fumes, exposure to petroleum industry chemicals, and being over the age of 55 years. Other risk factors include the appearance of white patches or spots in the mouth, known as leukoplakia,[18] which in about ⅓ of cases develops into cancer, and breathing or inhaling silica from cutting concrete, stone or cinder-blocks, especially in enclosed areas such as a warehouse, garage or basement. ## Diagnosis[edit] Left inferior internal jugular node metastases with extranodal invasion, two years after brachytherapy of tongue cancer. PET-CT scanning of a male in his 30s, 64 minutes after fludeoxyglucose (18F) was administered, shows some fluff around the tumor. A person usually presents to the physician complaining of one or more of the above symptoms. The person will typically undergo a needle biopsy of this lesion, and a histopathologic information is available, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the radiation oncologist, surgical oncologist, and medical oncologist.[medical citation needed] Most ( 90%) cancers of the head and neck are squamous cell-derived termed as "head and neck squamous-cell carcinomas".[6] ### Histopathology[edit] Throat cancers are classified according to their histology or cell structure, and are commonly referred to by their location in the oral cavity and neck. This is because where the cancer appears in the throat affects the prognosis - some throat cancers are more aggressive than others depending upon their location. The stage at which the cancer is diagnosed is also a critical factor in the prognosis of throat cancer. Treatment guidelines recommend routine testing for the presence of HPV for all oropharyngeal squamous cell carcinoma tumours.[51] #### Squamous-cell carcinoma[edit] Squamous-cell carcinoma is a cancer of the squamous cell – a kind of epithelial cell found in both the skin and mucous membranes. It accounts for over 90% of all head and neck cancers,[52] including more than 90% of throat cancer.[18] Squamous cell carcinoma is most likely to appear in males over 40 years of age with a history of heavy alcohol use coupled with smoking. The tumor marker Cyfra 21-1 may be useful in diagnosing squamous cell carcinoma of the head/neck (SCCHN).[53] #### Adenocarcinoma[edit] Adenocarcinoma is a cancer of epithelial tissue that has glandular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell-type).[52] ## Prevention[edit] Avoidance of recognised risk factors (as described above) is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity.[1] When diagnosed early, oral, head and neck cancers can be treated more easily and the chances of survival increase tremendously.[1] As of 2017 it was not known if existing HPV vaccines can help prevent head and neck cancer.[1] ## Management[edit] Improvements in diagnosis and local management, as well as targeted therapy, have led to improvements in quality of life and survival for people with head and neck cancer.[54] After a histologic diagnosis has been established and tumor extent determined, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, concomitant health problems, social and logistic factors, previous primary tumors, and the person's preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons and medical and radiation oncologists.[citation needed] Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. More extensive primary tumors, or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. More recently, as historical survival and control rates are recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens. ### Surgery[edit] Surgery as a treatment is frequently used in most types of head and neck cancer. Usually the goal is to remove the cancerous cells entirely. This can be particularly tricky if the cancer is near the larynx and can result in the person being unable to speak. Surgery is also commonly used to resect (remove) some or all of the cervical lymph nodes to prevent further spread of the disease. CO2 laser surgery is also another form of treatment. Transoral laser microsurgery allows surgeons to remove tumors from the voice box with no external incisions. It also allows access to tumors that are not reachable with robotic surgery. During the surgery, surgeon and pathologist work together to assess the adequacy of excision (“margin status”), minimizing the amount of normal tissue removed or damaged.[55] This technique helps give the person as much speech and swallowing function as possible after surgery.[56] ### Radiation therapy[edit] Radiation mask used in treatment of throat cancer Radiation therapy is the most common form of treatment. There are different forms of radiation therapy, including 3D conformal radiation therapy, intensity-modulated radiation therapy, particle beam therapy and brachytherapy, which are commonly used in the treatments of cancers of the head and neck. Most people with head and neck cancer who are treated in the United States and Europe are treated with intensity-modulated radiation therapy using high energy photons. At higher doses, head and neck radiation is associated with thyroid dysfunction and pituitary axis dysfunction.[57] Radiation therapy of head and neck cancers can also cause acute skin reactions of varying levels of severity, which can be treated and managed with topically applied creams or specialist films.[58] ### Chemotherapy[edit] Chemotherapy in throat cancer is not generally used to cure the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of paclitaxel and carboplatin. Cetuximab is also used in the treatment of throat cancer. Docetaxel-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only taxane approved by US FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced squamous cell carcinoma of the head and neck.[59] While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and salivary glands from the effects of radiation.[citation needed] There is no evidence that erythropoietin should be routinely given with radiotherapy.[60] ### Photodynamic therapy[edit] Photodynamic therapy may have promise in treating mucosal dysplasia and small head and neck tumors.[18] Amphinex is giving good results in early clinical trials for treatment of advanced head and neck cancer.[61] ### Targeted therapy[edit] Targeted therapy, according to the National Cancer Institute, is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some targeted therapy used in squamous cell cancers of the head and neck include cetuximab, bevacizumab and erlotinib. The best quality data are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone.[62] This study found that concurrent cetuximab and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in side effects, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. Whilst this study is of pivotal significance, interpretation is difficult since cetuximab-radiotherapy was not directly compared to chemoradiotherapy. The results of ongoing studies to clarify the role of cetuximab in this disease are awaited with interest. Another study evaluated the impact of adding cetuximab to conventional chemotherapy (cisplatin) versus cisplatin alone. This study found no improvement in survival or disease-free survival with the addition of cetuximab to the conventional chemotherapy.[63] However, another study which completed in March 2007 found that there was an improvement in survival.[citation needed] A 2010 review concluded that the combination of cetuximab and platin/5-fluorouracil should be considered the current standard first-line regimen.[64] Gendicine is a gene therapy that employs an adenovirus to deliver the tumor suppressor gene p53 to cells. It was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma.[65] The mutational profile of HPV\+ and HPV- head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases. [66][non-primary source needed] ### Immunotherapy[edit] Immunotherapy is a type of treatment that activates the immune system to fight cancer. One type of immunotherapy, immune checkpoint blockade, binds to and blocks inhibitory signals on immune cells to release their anti-cancer activities. In 2016, the FDA granted accelerated approval to pembrolizumab for the treatment of people with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.[67] Later that year, the FDA approved nivolumab for the treatment of recurrent or metastatic HNSCC with disease progression on or after platinum-based chemotherapy.[68] In 2019, the FDA approved pembrolizumab for the first-line treatment of metastatic or unresectable recurrent HNSCC.[69] ### Treatment side effects[edit] Depending on the treatment used, people with head and neck cancer may experience the following symptoms and treatment side effects:[18][58] * Eating problems * Pain associated with lesions * Mucositis * Nephrotoxicity and ototoxicity * Xerostomia * Gastroesophageal reflux * Radiation-induced osteonecrosis of the jaw * Radiation-induced acute skin reactions ### Psychosocial[edit] Programs to support the emotional and social well-being of people who have been diagnosed with head and neck cancer may be offered.[70] There is no clear evidence on the effectiveness of these interventions or any particular type of psychosocial program or length of time that is the most helpful for those with head and neck cancer.[70] ## Prognosis[edit] Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of people with head and neck cancer present with advanced disease.[71] Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement. (citation needed). HPV-associated oropharyngeal cancer has been shown to respond better to chemoradiation and, subsequently, a better prognosis, compared to non-associated HPV head and neck cancer.[7] Consensus panels in America (AJCC) and Europe (UICC) have established staging systems for head and neck squamous-cell cancers. These staging systems attempt to standardize clinical trial criteria for research studies, and attempt to define prognostic categories of disease. Squamous cell cancers of the head and neck are staged according to the TNM classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a “stage” of the cancer, from I to IVB.[72] ### Problem of second primaries[edit] Survival advantages provided by new treatment modalities have been undermined by the significant percentage of people cured of head and neck squamous cell carcinoma (HNSCC) who subsequently develop second primary tumors. The incidence of second primary tumors ranges in studies from 9%[73] to 23%[74] at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage HNSCC.[75] Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization. ### Digestive system[edit] Many people with head and neck cancer are also not able to eat sufficiently. A tumor may impair a person's ability to swallow and eat, and throat cancer may affect the digestive system. The difficulty in swallowing can lead to a person to choke on their food in the early stages of digestion and interfere with the food's smooth travels down into the esophagus and beyond. The treatments for throat cancer can also be harmful to the digestive system as well as other body systems. Radiation therapy can lead to nausea and vomiting, which can deprive a body of vital fluids (although these may be obtained through intravenous fluids if necessary). Frequent vomiting can lead to an electrolyte imbalance which has serious consequences for the proper functioning of the heart. Frequent vomiting can also upset the balance of stomach acids which has a negative impact on the digestive system, especially the lining of the stomach and esophagus. Enteral feeding, a method that adds nutrients directly into a person's stomach using a nasogastric feeding tube or a gastrostomy tube, may be necessary for some people.[76] Further research is required to determine the most effective method of enteral feeding to ensure that people undergoing radiotherapy or chemoradiation treatment are able to stay nourished during their treatment.[76] ### Respiratory system[edit] In the cases of some throat cancers, the air passages in the mouth and behind the nose may become blocked from lumps or the swelling from the open sores. If the throat cancer is near the bottom of the throat, it has a high likelihood of spreading to the lungs and interfering with the person's ability to breathe; this is even more likely if the person is a smoker, because they are highly susceptible to lung cancer. ### Mental health[edit] Cancer in the head or neck may impact a person's mental well being and can sometimes lead to social isolation.[70] This largely results from decreased ability or inability to eat, speak or effectively communicate. Physical appearance is often altered by both the cancer itself or as a consequence of treatment side effects. Psychological distress may occur and feelings such as uncertainty and fear may arise.[70] Some people may also have a changed physical appearance, differences in swallowing or breathing, and residual pain to manage.[70] #### Patient Experience[edit] Increased Caregiver Distress Unique to care for Head and Neck Cancer Patients Multiple studies have shown caregivers for head and neck cancer patients show higher rates of distress and poorer mental health compared to both the general population as well as those caring for non-head-and-neck cancer patients.[77] The high symptom burden patients' experience necessitate complex caregiver roles, often requiring hospital staff training, which caregivers can find distressing when asked to do so for the first time. It is becoming increasingly apparent caregivers (most often spouses, children or close family members) might not be adequately informed about, nor prepared or trained for the tasks and roles he/she will encounter during the treatment and recovery phase for this unique patient population, which span both technical and emotional support.[78] Of note, caregivers of patient's who report lower quality of life, demonstrate increased burden and fatigue that extents beyond the treatment phase. Examples of technically difficult caregiver duties include: tube feeding, oral suctioning, wound maintenance, medication delivery safe for tube feeding, and trouble shooting at home medical equipment. If the cancer affect the mouth or larynx, caregivers must also find a way to effectively communicate amongst themselves and with their healthcare team. This is in addition to providing emotional support for the person undergoing cancer therapy.[78] ### Others[edit] Like any cancer, metastasization affects many areas of the body, as the cancer spreads from cell to cell and organ to organ. For example, if it spreads to the bone marrow, it will prevent the body from producing enough red blood cells and affects the proper functioning of the white blood cells and the body's immune system; spreading to the circulatory system will prevent oxygen from being transported to all the cells of the body; and throat cancer can throw the nervous system into chaos, making it unable to properly regulate and control the body. ## Epidemiology[edit] Age-standardized death from oro-pharyngeal per 100,000 inhabitants in 2004.[79] no data less than 2 2-4 4-6 6-8 8-10 10-12 12-14 14-16 16-18 18-20 20-25 more than 25 The number of new cases of head and neck cancers in the United States was 40,490 in 2006, accounting for about 3% of adult malignancies. A total of 11,170 people died of their disease in 2006.[80] The worldwide incidence exceeds half a million cases annually. In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically nasopharyngeal cancer, is the most-common cause of death in young men.[81] * In 2008, there were 22,900 cases of oral cavity cancer, 12,250 cases of laryngeal cancer, and 12,410 cases of pharyngeal cancer in the United States.[18] * In 2002, 7,400 Americans were projected to die of these cancers.[82] * More than 70% of throat cancers are at an advanced stage when discovered.[83] * Men are 89% more likely than women to be diagnosed with, and are almost twice as likely to die of these cancers.[82] * African Americans are disproportionately affected by head and neck cancer, with younger ages of incidence, increased mortality, and more advanced disease at presentation.[71] Laryngeal cancer incidence is higher in African Americans relative to white, Asian, and Hispanic populations. There is a lower survival rate for similar tumor states in African Americans with head and neck cancer.[18] * Smoking and tobacco use are directly related to oropharyngeal (throat) cancer deaths.[84] * The risk of developing head and neck cancers increases with age, especially after 50 years. Most people who do so are between 50 and 70 years old.[18] ## Research[edit] Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers.[85] ## References[edit] 1. ^ a b c d e f g h i j k l "Oropharyngeal Cancer Treatment (Adult) (PDQ®)–Patient Version". National Cancer Institute. 22 November 2019. Retrieved 28 November 2019. 2. ^ a b c d e f g World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.8. ISBN 978-9283204299. 3. ^ GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). 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PMID 29208439. ## External links[edit] Wikimedia Commons has media related to Head and neck cancer. * Head and Neck Cancer at MedlinePlus (National Library of Medicine) * Head and Neck Cancer Treatment at RadiologyInfo * Head and Neck Cancer at Cancer.net (American Society of Clinical Oncology) Classification D * ICD-10: C07-C14 C32-C33 * ICD-9-CM: 140-149 * MeSH: D006258 External resources * Patient UK: Head and neck cancer * v * t * e Overview of tumors, cancer and oncology Conditions Benign tumors * Hyperplasia * Cyst * Pseudocyst * Hamartoma Malignant progression * Dysplasia * Carcinoma in situ * Cancer * Metastasis * Primary tumor * Sentinel lymph node Topography * Head and neck (oral, nasopharyngeal) * Digestive system * Respiratory system * Bone * Skin * Blood * Urogenital * Nervous system * Endocrine system Histology * Carcinoma * Sarcoma * Blastoma * Papilloma * Adenoma Other * Precancerous condition * Paraneoplastic syndrome Staging/grading * TNM * Ann Arbor * Prostate cancer staging * Gleason grading system * Dukes classification Carcinogenesis * Cancer cell * Carcinogen * Tumor suppressor genes/oncogenes * Clonally transmissible cancer * Oncovirus * Carcinogenic bacteria Misc. * Research * Index of oncology articles * History * Cancer pain * Cancer and nausea * v * t * e Tumors of 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 * t * e Human papillomavirus Related diseases Cancers * Cervical cancer * cancers * Anal * Vaginal * Vulvar * Penile * Head and neck cancer (HPV-positive oropharyngeal cancer) Warts * * genital * plantar * flat * Laryngeal papillomatosis * Epidermodysplasia verruciformis * Focal epithelial hyperplasia * Papilloma Others Acrochordon (skin tags) Vaccine * HPV vaccines * Cervarix * Gardasil Screening * Pap test: * stain * Bethesda system * Cytopathology * Cytotechnology * Experimental techniques: * Speculoscopy * Cervicography Colposcopy Biopsy histology * Cervical intraepithelial neoplasia (CIN) * Koilocyte * Vaginal intraepithelial neoplasia (VAIN) * Vulvar intraepithelial neoplasia (VIN) Treatment * Cervical conization * Loop electrical excision procedure (LEEP) History * Georgios Papanikolaou * Harald zur Hausen Authority control * LCCN: sh85059470 * NDL: 01184870 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: 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[FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Head and neck cancer	c0018671	30,027	wikipedia	https://en.wikipedia.org/wiki/Head_and_neck_cancer	2021-01-18T18:48:08	{"gard": ["12425"], "mesh": ["D006258"], "umls": ["C0018671"], "icd-9": ["149", "143", "146", "142", "140", "141", "145", "144", "148", "147"], "icd-10": ["C07", "C33", "C14", "C32"], "orphanet": ["290849"], "wikidata": ["Q1783924"]}
Acrogeria Other namesAcrogeria, Gottron type, Gottron's syndrome[1] Collagen(which is below normal/damaged in this condition)[2] SpecialtyDermatology Acrogeria (Gottron's syndrome) is a skin condition characterized by premature aging, more especially in the form of unusually fragile, thin skin on the hands and feet (distal extremities).[1] The prefix "acro" stems from the Greek akros which alludes to "extremity, tip" while the suffix "geria" comes from the Greek gerôn which means "elder". This is one of the classic congenital premature aging syndromes, occurring early in life, others being pangeria (Werner's syndrome) and progeria (Hutchinson–Gilford's syndrome), and was characterized in 1940.[3] Onset is in early childhood, it progresses over the next few years and then remains stable over time with morphology, colour and site remaining constant. A bruising tendency has been observed.[4] It is believed that Gottron syndrome may affect more females than males. Approximately forty cases have been reported in the medical literature, since the discovery of the disorder. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] This disorder is characterized by a reduction and loss of subcutaneous fat and collagen of the hands and feet, above all. It can be defined as a mild, nonprogressive, congenital form of premature skin senility due to the disappearance of the fatty tissue directly under the skin.[citation needed] More precisely, skin lesions deal with large, fixed, geographic and symmetrical fine scaly recessive erythematous plaques distributed over the dorsal side of distal extremities.[citation needed] Skin lesions can be associated with osteoarticular alterations. Other outcomes and observations may include abnormally small hands and feet with unusually prominent veins on the upper trunk (chest), short stature, and, sometimes, abnormally small jaw (micrognathia). Most of the cases analyzed show atrophy of the skin at the tip of the nose, which gives a sculptural appearance.[citation needed]The nails may be dystrophic or thick, but, most of the time, they are normal. In the skin histopathology, there is atrophy of the dermis and subcutaneum. The collagen fibers are loose and dispersed, and the elastic fibers are always fragmented. However, the epidermis is not affected.[citation needed] Although some patients present clinical features similar to those of progeria and metageria, they do not usually show generalized atherosclerosis. Therefore, they do not usually have premature myocardiac or coronary disease.[citation needed] ## Causes[edit] The cause of acrogeria is still not well determined. This disorder is thought to be inherited as an autosomal recessive genetic trait. However, the mode of genetic inheritance is not accurately known. It has been considered autosomal dominant and autosomal recessive, though most reported cases own a positive family background.[citation needed] Mutations in the COL3A1 gene, located at chromosome 2q31–q32, have been reported in varied phenotypes, including acrogeria and vascular rupture in Ehlers-Danlos' syndrome (more especially type IV).[5] In the fibroblast culture, a reduction of RNA messenger cells in collagen types I and II was found, as well as reduced life expectancy of the fibroblasts most prematurely showing morphological alterations typical of aging. This seems perfectly compatible with the patients' aged phenotype.[citation needed] ## Diagnosis[edit] X-ray applications on most cases have brought about little outcome in most of the published case reports. As a consequence, a certain number of authors consider acrogeria mainly as a cutaneous affection, but the bone alterations are well described as part of the syndrome.For patients who show typical alterations of acrogeria and metageria, in a concomitant way, the single term of "Acrometageria" has been proposed, which can refer to the widest spectrum of premature ageing syndromes. However, this concept is still not generally accepted in the medical literature.[citation needed]As these are extremely rare syndromes, all sharing an aspect of aging skin similar to progeria, they are also called progeroid syndromes, from time to time. ## Treatment[edit] There is currently no specific treatment available for either of these so-called progeroid syndromes. With this in mind, what is most important when making a differential diagnosis with them is based on the prognosis, which appears to be far better in acrogeria.[citation needed] ## Epidemiology[edit] Acrogeria is extremely rare, with only about 40 cases having been reported in the medical literature, since 1941.[citation needed] ## History[edit] Acrogeria was originally described by Gottron in 1941, when he noticed premature cutaneous aging localized on the hands and feet in two brothers, which were present ever since birth.[3] From that time, various cases have been published, most in the European literature and predominantly affecting women. Most patients were of short stature although a few were of normal height.[citation needed] ## See also[edit] * Hutchinson–Gilford 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 978-1-4160-2999-1. 2. ^ Patterson, James W. (2014). Weedon's Skin Pathology E-Book. Elsevier Health Sciences. p. 379. ISBN 9780702062001. Retrieved 28 December 2017. 3. ^ a b Gottron, H. Familiaere Akrogerie. Arch. Derm. Syph. 181: 571-583, 1940. 4. ^ Blaszczyk M, Depaepe A, Nuytinck L, Glinska-Ferenz M, Jablonska S (2000). "Acrogeria of the Gottron type in a mother and son". Eur J Dermatol. 10 (1): 36–40. PMID 10694296. 5. ^ Pope FM, Narcisi P, Nicholls AC, et al. (1996). "COL3A1 mutations cause variable clinical phenotypes including acrogeria and vascular rupture". Br J Dermatol. 135 (2): 163–181. doi:10.1046/j.1365-2133.1996.d01-971.x. PMID 8881656. ## External links[edit] * Familial acrogeria in a brother and sister Classification D * OMIM: 201200 * MeSH: C538187 External resources * Orphanet: 2500 * v * t * e Disorders involving multiple endocrine glands * Autoimmune polyendocrine syndrome * APS1 * APS2 * Carcinoid syndrome * Multiple endocrine neoplasia * 1 * 2A * 2B * Progeria * Werner syndrome * Acrogeria * Metageria * Woodhouse–Sakati syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acrogeria	c0238590	30,028	wikipedia	https://en.wikipedia.org/wiki/Acrogeria	2021-01-18T18:56:18	{"mesh": ["C538187"], "orphanet": ["2500"], "wikidata": ["Q4675775"]}
Lewin and Hughes (1987) presented the cases of a male-female sib pair with 'arthrogryposis,' hypotonia-hypokinesia sequence, and lymphedema. The parents were Ashkenazi Jewish. The authors suggested that the condition in these sibs was the same as that described by German et al. (1975). The boy died at age 2 years of cor pulmonale; the girl was stillborn. This was the first instance of affected sibs. Three of the 4 known families with affected children have been Ashkenazi Jews. Cardiac \- Cor pulmonale Skel \- Arthrogryposis Inheritance \- Autosomal recessive Neuro \- Hypotonia-hypokinesia sequence Skin \- Lymphedema ▲ 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	GERMAN SYNDROME	c3887495	30,029	omim	https://www.omim.org/entry/231080	2019-09-22T16:27:35	{"mesh": ["C562543"], "omim": ["231080"], "orphanet": ["2077"]}
A number sign (#) is used with this entry because of evidence that cryptorchidism can be caused by heterozygous mutation in the insulin-like-3 gene (INSL3; 146738) on chromosome 19p13. Description Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002). Clinical Features Bishop et al. (1979) pointed out that renal anomalies such as renal agenesis are often associated with the familial form of cryptorchidism. Czeizel et al. (1981) found that mothers of index cases had shorter menses and delayed menarche, and stated that 'pituitary hypogonadism of mothers seems to be a predisposing factor for undescended testes in their sons.' In 8 patients with mutations in either the INSL3 or LGR8 (RXFP2; 606655) genes, Ferlin et al. (2003) found different phenotypes ranging from normozoospermia to complete azoospermia and from bilateral cryptorchidism to retractile testes. The endocrine function of the testis appeared normal in all patients. Inheritance Corbus and O'Conor (1922) found several reports of families with multiple generations affected. Perrett and O'Rourke (1969) described ipsilateral (right-sided) cryptorchidism in 8 males in 4 generations. Pardo-Mindan et al. (1975) reported 2 families suggesting autosomal dominant or, as they correctly indicated, Y-linked inheritance. Czeizel et al. (1981) confirmed undescended testis in 1.5 to 4.0% of fathers and 6.2% of brothers. The family clustering fitted a gaussian-additive-multifactorial-threshold model. Heritability in first-degree male relatives was estimated to be 0.67 plus or minus 0.16. Bilateral (more severe) cryptorchidism was associated with a higher recurrence risk for brothers. The nosologic identity of unilateral and bilateral cryptorchidism was borne out by the study. Molecular Genetics Tomboc et al. (2000) used SSCP analysis to screen the coding regions of the INSL3 gene in genomic DNA samples obtained from 145 formerly cryptorchid patients and 36 adult male controls. Two mutations and several polymorphisms were identified. The authors concluded that the frequency of INSL3 gene mutations as a cause of cryptorchidism is low, because only 2 of 145 (1.4%) formerly cryptorchid patients were found to have mutations: arg49 to ter (R49X; 146738.0005), which was likely to be pathogenetic because it was found in a boy with undescended right testis and history of incarcerated right inguinal hernia, and pro69 to leu (P69L; 146738.0002), which was found in an 8-month-old baby with nonpalpable intraabdominal right testis. Canto et al. (2003) studied genomic DNA from 150 patients with idiopathic cryptorchidism. A heterozygous asn86-to-lys mutation (146738.0001) in the INSL3 gene was found in 1 patient whose mother was a heterozygous carrier of the mutation and whose father was homozygous wildtype. Ferlin et al. (2003) sequenced the INSL3 and LGR8 genes in 87 patients with corrected cryptorchidism and 80 controls and found 3 mutations in the INSL3 gene (146738.0002-146738.0004) in 4 patients and 1 LGR8 mutation (606655.0001) in 4. The authors concluded that INSL3-LGR8 mutations are frequently associated with human cryptorchidism and are maternally inherited. The only clinical consequence of alterations of the INSL3-LGR8 system seemed to be failure of the testis to descend normally into the scrotum during embryonic development, without affecting the spermatogenic and endocrine components of the testis itself. ### Associations Pending Confirmation For discussion of a possible association between cryptorchidism and mutation in the LGR8 gene, see 606655.0001. Animal Model Male Insl3 knockout mice exhibit bilateral abdominal cryptorchidism (Nef and Parada, 1999; Zimmermann et al., 1999). Overbeek et al. (2001) described mice with a transgene insertional mutation, crsp, causing high, intraabdominal cryptorchidism in homozygous males. The authors identified a candidate gene within a 550-kb deleted region, which they dubbed Great (G-protein-coupled receptor affecting testis descent). This gene was later identified as the murine ortholog of LGR8. Gorlov et al. (2002) described a targeted mutation in Great causing cryptorchidism in homozygous male mice. INHERITANCE \- Autosomal dominant GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism, unilateral or bilateral \- Oligozoospermia, mild (in some patients) \- Normozoospermia (in some patients) MISCELLANEOUS \- Mutations are frequently maternally inherited MOLECULAR BASIS \- Caused by mutation in the insulin-like 3 gene (INSL3, 146738.0001 ) ▲ 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	CRYPTORCHIDISM, UNILATERAL OR BILATERAL	c0010417	30,030	omim	https://www.omim.org/entry/219050	2019-09-22T16:29:11	{"doid": ["11383"], "mesh": ["D003456"], "omim": ["219050"], "icd-9": ["752.51"], "icd-10": ["Q53.9"], "synonyms": ["Alternative titles", "UNDESCENDED TESTIS"]}
A number sign (#) is used with this entry because of evidence that Meckel syndrome type 3 (MKS3) is caused by homozygous or compound heterozygous mutation in the TMEM67 gene (609884) on chromosome 8q22. Description Meckel syndrome is an autosomal recessive pre- or perinatal lethal malformation syndrome characterized by renal cystic dysplasia and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Smith et al., 2006). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000). Clinical Features Morgan et al. (2002) stated that comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2 (603194)-linked kindreds suggested that polydactyly, and possibly encephalocele, are less common in MKS3-linked families. Consugar et al. (2007) observed that polydactyly and occipital encephalocele were less common in MKS3 compared to MKS1. Mapping By a genomewide linkage search using homozygosity mapping in 8 consanguineous kindreds with MKS originating from the Indian subcontinent, Morgan et al. (2002) identified an MKS locus (MKS3) on chromosome 8q24, with a maximum cumulative 2-point lod score of 3.04 at theta = 0.06 with marker D8S1179. Heterozygosity tests provided evidence of 1 unlinked family. Exclusion of this family for multipoint analysis maximized the cumulative multipoint lod score to 5.65 with marker D8S1128. Smith et al. (2006) refined MKS3 mapping to a 12.67-Mb interval (8q21.3-q22.1) that shows homology of synteny to the Wpk locus in rat. Molecular Genetics Smith et al. (2006) sequenced the human ortholog of rat Wpk, TMEM67 (609884), and found different pathogenic mutations in 5 MKS3 families. Consistent with the consanguineous nature of these families, all the mutations were homozygous. Consugar et al. (2007) identified 7 novel pathogenic mutations in the TMEM67 gene (see, e.g., 609884.0011) in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All 5 families were of European origin. In a patient from a consanguineous family who presented with MKS3 and cerebellar heterotopia, Adams et al. (2012) identified a homozygous deletion in the C-terminal region of meckelin (609884.0025). The deletion abrogated the interaction of meckelin with filamin A (FLNA; 300017), resulting in aberrant hyperactivation of canonical Wnt signaling in patient fibroblasts compared with controls. Heterogeneity Shaheen et al. (2011) identified a consanguineous Arab family in whom the Meckel-Gruber syndrome phenotype mapped to the MKS3 locus but in whom no mutation in the TMEM67 gene was found. Animal Model The Wpk rat was originally suggested to be a model system for autosomal recessive polycystic kidney disease (see 263200) (Nauta et al., 2000), but further characterization of the phenotype demonstrated central nervous system malformations, including hypoplasia to agenesis of the corpus callosum with severe hydrocephaly (Nauta et al., 2000; Gattone et al., 2004). Smith et al. (2006) refined the mapping of the Wpk locus and analyzed the annotated genomic sequence, showing that the critical region contained 13 genes conserved in the syntenic mouse and human regions. Sequence analysis of a novel gene in the mutant rat showed a nonconservative substitution, P394L, in exon 12 that was not present in the parental Wistar strain. INHERITANCE \- Autosomal recessive HEAD & NECK Mouth \- Cleft palate (in some patients) ABDOMEN Liver \- Hepatic developmental defects \- Bile duct proliferation \- Ductal plate malformation \- Hepatic fibrosis GENITOURINARY Kidneys \- Cystic dysplasia SKELETAL Hands \- Polydactyly, postaxial Feet \- Polydactyly, postaxial NEUROLOGIC Central Nervous System \- Encephalocele, occipital \- Dandy-Walker malformation (in some patients) \- Hydrocephalus (in some patients) MISCELLANEOUS \- Lethal in utero or in the perinatal period MOLECULAR BASIS \- Caused by mutation in the transmembrane protein 67 gene (TMEM67, 609884.0001 ) ▲ 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	MECKEL SYNDROME, TYPE 3	c0265215	30,031	omim	https://www.omim.org/entry/607361	2019-09-22T16:09:19	{"doid": ["0070117"], "omim": ["607361"], "orphanet": ["564"], "synonyms": ["Alternative titles", "MECKEL-GRUBER SYNDROME, TYPE 3"]}
A syndrome that is characterized by woolly hair, palmoplantar keratoderma and dilated cardiomyopathy principally affecting the left ventricle. ## Epidemiology Only a few cases have been reported, all involving patients from Ecuador, India or Turkey. ## Clinical description The woolly hair is present at birth and the palmoplantar keratoderma appears during the first year of life. The cardiac anomaly presents during childhood and is marked by dilation of the left ventricle accompanied by alterations in muscle contractility. The dilated cardiomyopathy may lead to life-threatening congestive heart failure. ## Etiology The syndrome is transmitted as an autosomal recessive trait and is caused by mutations in the DSP gene (6p24) encoding desmoplakin, a protein involved in cell adhesion. ## Differential diagnosis The syndrome is similar to Naxos disease (see this term). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Carvajal syndrome	c1854063	30,032	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65282	2021-01-23T18:46:35	{"gard": ["5595"], "mesh": ["C535581"], "omim": ["605676", "615821"], "umls": ["C1854063"], "synonyms": ["KWWH type II", "Keratoderma with woolly hair type II", "Woolly hair-palmoplantar hyperkeratosis-dilated cardiomyopathy syndrome", "Woolly hair-palmoplantar keratoderma-dilated cardiomyopathy syndrome", "Wooly hair-palmoplantar hyperkeratosis-dilated cardiomyopathy syndrome", "Wooly hair-palmoplantar keratoderma-dilated cardiomyopathy syndrome"]}
By electrophoresis of human tears on slab polyacrylamide gels, Azen (1976) demonstrated polymorphism of anodally migrating proteins. Family studies indicated simple codominant inheritance. Population frequency data were given. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TEAR PROTEIN, ANODAL	c1861283	30,033	omim	https://www.omim.org/entry/186890	2019-09-22T16:32:58	{"omim": ["186890"]}
A number sign (#) is used with this entry because this form of neurodegeneration with brain iron accumulation (NBIA), referred to here as NBIA2B, is caused by homozygous or compound heterozygous mutation in the PLA2G6 gene (603604) on chromosome 22q13. See NOMENCLATURE section below. This disorder is also referred to as 'atypical neuroaxonal dystrophy' to distinguish it from the allelic disorder 'infantile neuroaxonal dystrophy,' (INAD1, NBIA2A; 256600), which shows earlier onset and a more homogeneous phenotype (Gregory et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200). Clinical Features Morgan et al. (2006) studied a consanguineous Pakistani family with NBIA with 7 affected individuals in 5 generations. Affected individuals had abnormal iron accumulation in the globus pallidus, demonstrated by T2-weighted magnetic resonance imaging (MRI). The appearance was distinct from the 'eye of the tiger' sign seen in NBIA1 and Karak syndrome. Gregory et al. (2008) found that individuals with NBIA due to PLA2G6 mutations had widely varying phenotypes. They reported 6 affected individuals from 4 families. The average age at onset was 4.4 years. Presenting factors included gait instability or ataxia and speech delay; 2 were also noted to have diminished social interaction. Two-thirds of the patients had optic atrophy. Other features included spastic or areflexic tetraparesis, nystagmus, and seizures. Truncal hypotonia and strabismus were not observed. The natural history was characterized by progressive dystonia and dysarthria, as well as by neurobehavioral disturbances, including impulsivity, distractibility, poor attention span, hyperactivity, and emotional lability. Brain MRI showed cerebellar atrophy with high iron content in the globus pallidus. One of the patients reported by Gregory et al. (2008) was compound heterozygous for 2 mutations in the PLA2G6 gene (603604.0007 and 603604.0008). She presented at 3 years of age with toe walking and lower extremity spasticity. She developed optic atrophy and became nonambulatory by 5 years of age with dystonia and dysarthria, progressing to profound sensorimotor impairment by age 9 years. She died at age 23 years. Postmortem examination showed generalized brain atrophy with neuronal loss and gliosis. There were axonal swellings throughout the cortex, striatum, cerebellum, brainstem, and spinal cord. There were also Lewy bodies and neurofibrillary tangles, as seen in Parkinson disease (PD; 168600) and Alzheimer disease (AD; 104300), respectively. ### Karak Syndrome In a family living in Karak, a town in southern Jordan, Mubaidin et al. (2003) observed 2 sons of consanguineous parents who showed early-onset progressive cerebellar ataxia, dystonia, spasticity, and intellectual decline. Neuroradiology showed cerebellar atrophy and features compatible with iron deposition in the putamen (including the 'eye of the tiger' sign) and substantia nigra. Although X-linked recessive inheritance was possible, the consanguinity and lack of other affected males in the maternal line favored autosomal recessive inheritance. Linkage analysis excluded a mutation in the PANK2 gene (606157). Mubaidin et al. (2003) suggested that this disorder, which they termed 'Karak syndrome,' was novel and a member of a family of neurologic diseases involving excess cerebral iron accumulation, including, in addition to NBIA1, neuroferritinopathy (606159), aceruloplasminemia (604290), and Friedreich ataxia (229300). In a review of NBIA, Gregory et al. (2009) stated that Karak syndrome falls into the phenotypic spectrum of atypical neuroaxonal dystrophy. Mapping In the Pakistani family with NBIA studied by them, Morgan et al. (2006) detected linkage to chromosome 22q12-q13 (lod 4.65), with a minimal region of linkage of 4.9Mb between D22S426 and D22S276 containing the disease locus. Molecular Genetics In the index patient from a large Pakistani family with NBIA, Morgan et al. (2006) found a homozygous missense mutation in the PLA2G6 gene (603604.0002). The mutation segregated with disease status in 15 affected and unaffected family members. Gregory et al. (2008) found PLA2G6 mutations in 45 (79%) of 56 patients with INAD1 (NBIA2A) and in 6 (20%) of 23 patients with NBIA2B (see, e.g., 603604.0006-603604.0008). Patients with the less severe phenotype tended to have compound heterozygous missense mutations, consistent with residual protein function. ### Karak Syndrome Morgan et al. (2006) demonstrated that the affected members of the kindred on the basis of which the Karak syndrome was named had a homozygous missense mutation in the PLA2G6 gene (603604.0005). Nomenclature This disorder, caused by mutation in the PLA2G6 gene, is referred to in OMIM as NBIA2B, since the original phenotype was described as a form of neurodegeneration with brain iron accumulation (NBIA; Morgan et al., 2006). Some references in the literature (see, e.g., Chinnery et al., 2007) use the designation 'NBIA2' to refer to a similar disorder caused by mutation in the FTL gene (134790). OMIM refers to NBIA caused by mutation in the FTL gene as NBIA3 (606159). Kurian et al. (2008) proposed that disorders resulting from mutation in the PLA2G6 gene be referred to as PLA2G6-associated neurodegeneration (PLAN). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Impaired smooth pursuit \- Abnormal saccades \- Nystagmus \- Optic atrophy (67%) ABDOMEN Gastrointestinal \- Dysphagia \- Feeding difficulties SKELETAL Feet \- Pes calcaneovarus NEUROLOGIC Central Nervous System \- Gait ataxia \- Cerebellar ataxia \- Dysmetria \- Dysdiadochokinesia \- Intention tremor \- Extrapyramidal features \- Chorea of all limbs \- Progressive loss of movement control \- Dystonia \- Dysarthria \- Bradykinesia \- Hypertonia \- Spasticity \- Loss of independent ambulation within a few years \- Extensor plantar responses \- Speech delay \- Seizures \- Cognitive decline \- Cerebellar atrophy \- Increased iron deposition in the basal ganglia \- Cerebral atrophy \- 'Eye of the tiger' sign on MRI \- Axonal swellings or spheroids \- Lewy bodies in the substantia nigra \- Lewy bodies throughout the brain \- Neurofibrillary tangles Behavioral Psychiatric Manifestations \- Diminished social interaction \- Autistic features \- Impulsivity \- Poor attention span \- Hyperactivity \- Emotional lability MISCELLANEOUS \- Childhood onset (average 4 to 6 years) \- Progressive disorder \- Variable phenotype \- Allelic disorder to infantile neuroaxonal dystrophy ( 256600 ) MOLECULAR BASIS \- Caused by mutation in the phospholipase A2, group VI gene (PLA2G6, 603604.0002 ) ▲ 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	NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B	c0270724	30,034	omim	https://www.omim.org/entry/610217	2019-09-22T16:04:55	{"doid": ["0110736"], "mesh": ["D019150"], "omim": ["610217"], "orphanet": ["35069"], "synonyms": ["Alternative titles", "NEURODEGENERATION WITH BRAIN IRON ACCUMULATION, PLA2G6-RELATED", "NEUROAXONAL DYSTROPHY, ATYPICAL"], "genereviews": ["NBK1675"]}
A hydatidiform mole is a benign gestational trophoblastic disease developing during pregnancy. Resulting from an abnormal fertilization characterized by trophoblastic proliferation, normal embryo development is rendered impossible. Hydatidiform moles can be either complete or partial. ## Epidemiology The condition appears to occur in approximately 1/1,000 pregnancies and in 1/41 miscarriages in Europe. ## Clinical description Complete moles are asymptomatic in 40% of cases. Most often, a mole is detected upon suspicion of miscarriage in the first trimester, with bleeding and pelvic pain. The clinical signs in the second trimester (vomiting, metrorrhagia, abnormal increase in the size of the uterus, and more rarely anemia or preeclampsia) are observed less often, due to early detection by ultrasound examination. Hyperthyroidism is exceptional. The clinical signs of a partial mole (metrorrhagia, vomiting, etc.) are rare. A mole is usually detected histologically on analysis of aspiration samples from a suspected miscarriage. ## Etiology The moles are caused by abnormal fertilization with an excess of paternal chromosome material. Complete moles result from fertilization of an enucleated ovocyte by one or two haploid spermatozoa. The caryotype is 46,XX (75% of cases) or 46,XY (25%). The mole is characterized by trophoblastic hyperplasia associated with generalized degeneration of chorionic villi and absence of an amniotic cavity and embryonal tissue. Partial moles result from fertilization of a normal ovocyte by two spermatozoa or one abnormal spermatozoon. This type of mole is characterized by focal trophoblastic hyperplasia, localized degeneration of chorionic villi and identifiable embryonal tissue. The caryotype is triploid in 99% of cases. ## Diagnostic methods Ultrasound of a complete mole may show a classic ''snow storm'' appearance (solid, hyperechoic areas of varying forms interspersed with liquid areas of various sizes) occupying the entire uterine cavity. Earlier ultrasound before 9-10 weeks of pregnancy shows a limited vesicular appearance of the placenta. Ultrasound of a partial mole shows focal vesicular damage. Embryonic structures without an increase in uterine size are commonly found. Diagnosis is based on histological examination of the product of fertilization. Double reading by a pathology expert is often useful. When hydatidiform mole is suspected, determination of total chorionic gonadotropin (hCG) must be performed. ## Differential diagnosis Moles must not be confused with gestational trophoblastic neoplasms (see this term) nor with prolonged retention of a ''classic'' spontaneous miscarriage. ## Genetic counseling Aside from very rare cases of recurrent moles in the same patient or in the same family (< 1% of cases, in which a mutation in the NLRP7 or KHDC3L genes have sometimes been found), genetic counseling is not required. ## Management and treatment Treatment of moles consists of ultrasound-guided suction evacuation. Evacuation must be scheduled rapidly due to the risk of complications, which increases with gestational age. ## Prognosis After removal, the prognosis is excellent. The main risk is retention by incomplete aspiration (25% of cases) justifying ultrasound follow-up within 15 days of aspiration. Retention (ultrasound image of more than 17 mm in anteroposterior diameter) warrants a repeated aspiration. In about 15 % of cases of complete moles and in 0.5 to 5% of partial moles, the condition leads to gestational trophoblastic neoplasm (see this term) complications in the weeks and months following mole evacuation. Monitoring of plasma hCG levels allows diagnosis of possible occurrence of gestational trophoblastic neoplasm which would warrant disease staging and appropriate chemotherapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hydatidiform mole	c0020217	30,035	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99927	2021-01-23T17:23:53	{"gard": ["10263"], "mesh": ["D006828"], "omim": ["231090", "614293"], "umls": ["C0020217"], "icd-10": ["O01.0", "O01.1", "O01.9"], "synonyms": ["Molar pregnancy"]}
Roussy Levy syndrome is a term used to describe a neuromuscular disorder that typically becomes apparent during early childhood. This syndrome is considered a form of Charcot-Marie-Tooth (CMT) disease. Individuals with this disorder have clinical symptoms similar to Charcot-Marie-Tooth (CMT) disease type 1, which is characterized by muscle weakness and atrophy, poor judgement of movement (sensory ataxia), absent reflexes (areflexia) of the lower legs and hands, and abnormally high arches of the feet (pes cavus or "clawfoot"). Additional features of rhythmic shaking (static tremor) in the hands and an unsteady gait (gait ataxia) are specific to Roussy Levy syndrome. This disorder is caused by issues with nerve conduction and sensory dysfunction. Roussy Levy syndrome may result from a duplication of the PMP22 gene (which is also associated with CMT1A) or a mutation in the myelin protein zero (MPZ) gene (mutations in this gene are also associated with CMT1B). Roussy Levy syndrome is inherited in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Roussy Levy syndrome	c0205713	30,036	gard	https://rarediseases.info.nih.gov/diseases/4741/roussy-levy-syndrome	2021-01-18T17:57:52	{"mesh": ["D002607"], "omim": ["180800"], "umls": ["C0205713"], "orphanet": ["3115"], "synonyms": ["Roussy Levy hereditary areflexic dystasia", "Roussy-Levy disease", "Hereditary areflexic dystasia", "Charcot-Marie-Tooth Disease (Variant)", "Charcot-Marie-Tooth-Roussy-Levy Disease", "Hereditary Motor Sensory Neuropathy I", "HMSN I"]}
Ring chromosome 7 syndrome is a rare chromosomal anomaly syndrome, with highly variable phenotype, principally characterized by growth failure, short stature, intellectual disability, dermatological abnormalities (nevus flammeus, dark pigmented nevi, café-au-lait spots), microcephaly and facial dysmorphism (incl. facial asymmetry, small ears, abnormal palpebral fissures, ptosis, epicanthic folds, hyper/hypotelorism). Additional reported features include convulsions, cleft lip and palate, clinodactyly, kyphoscoliosis and genital anomalies (i.e. cryptorchidism, hypospadias, micropenis). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ring chromosome 7 syndrome	c0795818	30,037	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1449	2021-01-23T17:08:45	{"gard": ["1345"], "mesh": ["C537813"], "umls": ["C0795818", "C2931622"], "icd-10": ["Q93.2"], "synonyms": ["Ring 7", "Ring chromosome 7"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spondylocostal dysostosis-3 (SCDO3) is caused by homozygous or compound heterozygous mutation in the LFNG gene (602576) on chromosome 7p22. For a phenotypic description and a discussion of genetic heterogeneity of spondylocostal dysostosis, see 277300. Clinical Features Sparrow et al. (2006) reported a proband of Lebanese background who presented with extensive congenital vertebral anomalies; long, slender fingers; and camptodactyly of the left index finger. X-ray and magnetic resonance imaging (MRI) scans showed multiple vertebral ossification centers in the thoracic spine, which showed fitted angular shapes similar to those seen in the patient with spondylocostal dysostosis (SCDO2; see 608681) caused by mutation in the MESP2 gene (605195) (Whittock et al., 2004). Severe foreshortening of the spine was emphasized by comparison of the patient's arm span (186.5 cm) with adult height (155 cm; lower segment 92.5 cm). In contrast to SCDO2, vertebral anomalies were also present in the cervical and lumbar spine. Otomo et al. (2019) described a 9-month-old Japanese boy with a spinal deformity. His height was approximately -2.5 SD. He had multiple vertebral anomalies from cervical to sacral vertebrae as well as defect and fusion of ribs. Radiographs showed normal pelvis and long tubular bones, but a 'pebble-beach' appearance of the vertebral bodies. Lateral view of the cervical spine showed kyphosis and a hypoplastic odontoid process. Molecular Genetics In a Lebanese patient with spondylocostal dysostosis in whom mutations in the DLL3 (602768) and MESP2 genes were excluded, Sparrow et al. (2006) screened for mutations in the LFNG gene based on the phenotype of the homologous mouse mutant and identified a homozygous missense mutation (F188L; 602576.0001). Both parents with normal spinal and hand anatomy were heterozygous for the mutant allele. Based on comparison with the Lfng-null mouse, Sparrow et al. (2006) suggested that the hand anomalies in the proband were not caused by the LFNG mutation but were a secondary consequence of the cervical segmentation phenotype through nerve entrapment. In a 9-month-old Japanese boy with spondylocostal dysostosis, Otomo et al. (2019) found compound heterozygosity for a missense (D201N; 602576.0002) and a frameshift (602576.0003) mutation in the LFNG gene. Each parent was heterozygous for 1 of the mutations. Neither mutation was found in the ExAC, ESP6500, or iJGVD databases. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature CHEST Ribs Sternum Clavicles & Scapulae \- Fused ribs SKELETAL Spine \- Multiple vertebral anomalies \- Hypoplastic odontoid process \- 'Pebble-beach' appearance of vertebral bodies \- Multiple vertebral ossification centers \- Scoliosis, nonprogressive (cervical and thoracic) \- Kyphosis Pelvis \- Normal pelvis Limbs \- Normal long bones MISCELLANEOUS \- Two patients have been independently reported (last curated February 2019) MOLECULAR BASIS \- Caused by mutation in the lunatic fringe gene (LFNG, 602576.0001 ) ▲ 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	SPONDYLOCOSTAL DYSOSTOSIS 3, AUTOSOMAL RECESSIVE	c0265343	30,038	omim	https://www.omim.org/entry/609813	2019-09-22T16:05:33	{"doid": ["0050568"], "mesh": ["C537565"], "omim": ["609813"], "orphanet": ["2311"], "genereviews": ["NBK8828"]}
Masha and Dasha Krivoshlyapova Born Мария и Дарья Кривошляповы 3 January 1950 Moscow, Soviet Union Died17 April 2003(2003-04-17) (aged 53) Moscow, Russia Known forConjoined twins Maria and Daria ('Masha and Dasha') Krivoshlyapova (Мария и Дарья Кривошляповы) (3 January 1950 – 17 April 2003, Moscow) were Ischiopagus tripus conjoined twins from Russia. They were removed from their mother's custody at birth to be studied by Soviet physiologists. Their mother was told that her daughters had died soon after their birth. ## Contents * 1 Biography * 2 Early life * 3 Education * 4 Later life * 4.1 Death * 5 References and external links * 6 References ## Biography[edit] Masha and Dasha's mother, Yekaterina Krivoshlyapova, did not know she was having twins and spent two days and nights giving birth naturally. The doctors told her she had delivered a mutant (урод) and she was not shown the babies. They were born joined at the waist at a 180-degree angle with two heads, two torsos, four arms and one leg each, and a third, vestigial limb at their back that had some movement. ## Early life[edit] The Soviet physiologist Pyotr Anokhin was studying the separate roles of the nervous system and the blood system on the body's ability to adjust to conditions such as prolonged sleep deprivation, extreme hunger, and extreme temperature change. Conjoined twins who shared a blood system but had separate nervous systems were ideal objects for research. He had put out an alert to all maternity hospitals in the USSR to be informed if any conjoined twins were born, and began studying Masha and Dasha within days of their birth. When the twins were born, their mother was told they required full-time care from the State. She agreed, but on the condition that she would keep custody and visit them regularly. A night nurse brought the twins in to see their mother and let her hold them. Scientists did not want her to keep custody of them so she was later told by one of Anokhin's physiologists that they had died of pneumonia. In reality, the twins had been taken to the Institute of Experimental Medicine in Moscow to be studied and experimented on under laboratory conditions. The Soviet Academy of Medical Sciences produced a documentary film detailing the research.[1] In Autumn 1950, under Stalin's rule, Anokhin was exiled for two years for his anti-Soviet views on genetics (which taught Lysenkoism and Lamarckian evolution rather than Mendelian genetics and Darwinian evolution). The twins were placed in the Academy of Medical Sciences Pediatric Institute, where a team of Anokhin's physiologists continued to carry out experiments on them for the following six years; Masha and Dasha's case is now considered a prolonged case of medical torture. Experiments included packing one twin in ice to bring their temperature down to near-fatal levels while observing temperature changes in the other twin, burning them, starving them, depriving them of sleep and electrocuting them in time with a metronome to test their reflexes. Their lung, heart and brain activity was constantly monitored by pneumograms, electrocardiograms and encephalograms. Tubes were routinely inserted into their stomachs to monitor gastric juices and blood was taken from them three times a day. In 1956 they were transferred to the Central Scientific Research Institute of Traumatology and Orthopedics (TSNIIPP) (Центральный научно-исследовательский институт протезирования и протезостроения) in Moscow where they were taught to walk and given an elementary education. They were kept hidden from the public in a children's ward there for the following eight years. ## Education[edit] In 1964, news spread to Moscow that a girl with two heads was being kept in the Institute. As a result, the twins were transferred to a boarding school for children with motor-impairment in Novocherkassk, southern Russia, to continue their education. They studied here for four years in what they later recalled was the happiest time of their lives. In 1968 their third leg was amputated in an effort to make them less noticeable to the Soviet public, who were not used to seeing disabled people. The twins had by now developed very different personalities, with Masha being dominant, tomboyish and cheeky, and Dasha submissive, thoughtful and quiet. Dasha fell in love with a fellow student, but Masha put a stop to the romance. Dasha fell into a depression and tried to hang herself when the pair were 18.[2] This coincided with having been told by a medical commission which graded disability that they had been placed in the lowest grade, which meant that they would be kept for life in a retirement home (there were no homes for the disabled as the Soviet Union saw 'invalids' as flaws in the system) with no right to work or be independent in any way.[2] In 1989, aged 39, they moved into the 20th Home for Veterans of War and Labour and lived there in a small room with a single bed for the next fourteen years. They earned pocket money sewing diapers and assembling pipettes. They found their birth mother Yekaterina Krivoshlyapova in 1985 and she visited them for four years before Masha broke off the connection. They were visited every week by ‘Aunty Nadya’ – Nadezhda Gorokhova – their physiotherapist in TSNIIPP, who befriended them throughout their lives. With the coming of Gorbachev’s campaign of openness, or glasnost, they made an appeal on a national television chat show Vzglyad in 1988, to be allowed to leave the 20th Home which was being turned into a mental asylum. The appeal was successful and they moved to the 6th Home for Veterans of Labour with greatly improved living conditions and bought themselves luxuries such as a television set, an Atari, a music cassette player and a computer on the proceeds of charitable contributions. ## Later life[edit] They were also able to buy alcohol and over the next decade the twins became alcoholics - only Dasha drank, Masha was unable to because of a gag reflex. Because they shared the same blood supply, both would become inebriated. They made many attempts to stop drinking, which included hypnotism, magic spells and being 'sewn up', a process whereby a capsule (containing a nocebo chemical which would supposedly kill them upon inebriation) was inserted surgically under their skin. The pair visited Cologne, Germany, in August 1991. However, the trip was cut short following the Soviet coup attempt to overthrow Gorbachev. They befriended a British journalist, Juliet Butler, in 1988. The twins and Butler's family became close friends over the next twelve years, and she collaborated with them in appearing in a BBC Horizon documentary on conjoined twins in 1999.[3] Butler also helped write their autobiography, which was published in Germany in 2000.[4] She wrote a novel based on their life story called 'The Less you Know, The Sounder You Sleep' which was published in the UK, Australia, New Zealand, Canada, India, South Africa and the Netherlands in 2017.[2] British Surgeon Lewis Spitz, who specialised in operating on conjoined twins, offered to separate them in London, but Masha was against the procedure. ### Death[edit] Masha fell ill on the 13th of April, 2003, complaining of back pain. She died the following day, on the 14th of April, seventeen hours after the onset of her symptoms. Dasha was taken to the First City Hospital and died another seventeen hours later due to blood poisoning from the toxic by-products of Masha's decomposing body. At the time of their death they were the oldest living conjoined twins in the world. The pair were cremated and their remains lie in the Novodevichy Cemetery in Moscow. ## References and external links[edit] * Image ## References[edit] 1. ^ Krivoshlyapova, Masha/dasha. "Medical Documentary on conjoined twins". BIgnatiev. Retrieved 23 August 2017. 2. ^ a b c Butler, Juliet (2017-08-10). The Less You Know The Sounder You Sleep. Fourth Estate. ISBN 9780008203757. 3. ^ truthjunkie69 (2015-08-25), BBC Horizon - Conjoined Twins, retrieved 2017-07-10 4. ^ Butler, Juliet (2000). Masha und Dasha. Autobiographie eines siamesischen Zwillingspaars (in German). Bern München Wien. ISBN 9783502150978. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Masha and Dasha Krivoshlyapova	None	30,039	wikipedia	https://en.wikipedia.org/wiki/Masha_and_Dasha_Krivoshlyapova	2021-01-18T18:29:29	{"wikidata": ["Q1981369"]}
Solid, non-blisterform elevated areas in or under the skin Nodule SpecialtyDermatology In medicine, nodules are small firm lumps, usually greater than 1 cm in diameter.[1][2] If filled with fluid they are referred to as cysts.[2] Smaller (less than 0.5 cm) raised soft tissue bumps may be termed papules.[3] The evaluation of a skin nodule includes a description of its appearance, its location, how it feels to touch and any associated symptoms which may give clues to an underlying medical condition.[4] Nodules in skin include dermatofibroma[5] and pyogenic granuloma.[6] Nodules may form on tendons and muscles in response to injury,[7] and are frequently found on vocal cords.[8] They may occur in organs such as the lung,[9] or thyroid,[10] or be a sign in other medical conditions such as rheumatoid arthritis.[11] ## Contents * 1 Characteristics * 2 Evaluation * 3 Conditions * 3.1 Other examples * 4 Reference * 5 External links ## Characteristics[edit] Nodules are small firm lumps usually greater than 1 cm in diameter, found in skin and other organs.[1][2] If filled with fluid they are usually softer and referred to as cysts.[2] Smaller (less than 0.5 cm) raised soft tissue bumps may be termed papules.[3] ## Evaluation[edit] The evaluation of a skin nodule includes a description of its appearance, its location, how it feels to touch and any associated symptoms which may give clues to an underlying medical condition.[4] Often discovered unintentionally on a chest x-ray, a single nodule in the lung requires assessment to exclude cancer.[9] ## Conditions[edit] Nodules may form on tendons and muscles in response to injury,[7] and are frequently found on vocal cords,[8] They occur in conditions including endometriosis,[12] neurofibomatosis,[6] and in rheumatoid arthritis.[11] They may also feature in Kaposi's sarcoma[13] and gonorrhea.[14] ### Other examples[edit] * Dermatofibroma[5] * CT of thyroid colloid nodule with calcification[15][10] * lung nodule[16] * Merkel cell carcinoma[6] * Pyogenic granuloma[6] * lipoma[6] ## Reference[edit] 1. ^ a b Mosby (2013). Mosby's Medical Dictionary - E-Book. Elsevier. pp. 1235–1236. ISBN 978-0-323-11258-1. 2. ^ a b c d Oakley, Amanda. "Terminology in dermatology \| DermNet NZ". dermnetnz.org. Retrieved 13 January 2021. 3. ^ a b Potter, Patricia A.; Perry, Anne Griffin; Stockert, Patricia; Hall, Amy (2014-03-25). Essentials for Nursing Practice - E-Book. Elsevier Health Sciences. ISBN 978-0-323-18881-4. 4. ^ a b Evangelisto, Amy; Werth, Victoria; Schumacher, H. Ralph (October 2006). "What is that nodule? A diagnostic approach to evaluating subcutaneous and cutaneous nodules". Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases. 12 (5): 230–240. doi:10.1097/01.rhu.0000240034.72958.2f. ISSN 1076-1608. Retrieved 14 January 2021. 5. ^ a b Linton, Christina P. (March 2011). "Essential Morphologic Terms and Definitions". Journal of the Dermatology Nurses' Association. 3 (2): 102–103. doi:10.1097/JDN.0b013e318211c6f0. ISSN 1945-760X. Retrieved 13 January 2021. 6. ^ a b c d e "Dermal and subcutaneous lesions \| DermNet NZ". dermnetnz.org. Retrieved 13 January 2021. 7. ^ a b Ashton-Miller, James A. (1999). "Response of Muscle and Tendon to Injury and Overuse". National Academies Press (US). Retrieved 13 January 2021. Cite journal requires `\|journal=` (help) 8. ^ a b "BRITISH VOICE ASSOCIATION : Vocal nodules". www.britishvoiceassociation.org.uk. Retrieved 13 January 2021. 9. ^ a b Kikano, George E.; Fabien, Andre; Schilz, Robert (15 December 2015). "Evaluation of the Solitary Pulmonary Nodule". American Family Physician. 92 (12): 1084–1091. ISSN 0002-838X. Retrieved 14 January 2021. 10. ^ a b Britton, K. E.; Gilday, David L.; Maisey, Michael (2013-12-11). Clinical Nuclear Medicine. Springer. ISBN 978-1-4899-3358-4. 11. ^ a b "Rheumatoid nodules in rheumatoid arthritis (RA)". NRAS. Retrieved 13 January 2021. 12. ^ Nisenblat V, Bossuyt PM, Farquhar C, Johnson N, Hull ML (February 2016). "Imaging modalities for the non-invasive diagnosis of endometriosis". The Cochrane Database of Systematic Reviews. 2. doi:10.1002/14651858.cd009591.pub2. PMC 7100540. PMID 26919512. "painful palpable nodules" 13. ^ Massi, Daniela; Luzar, Boštjan; Alos, Llucia (2016). "15. Common skin tumours of the head and neck". In Cardesa, Antonio; Slootweg, Pieter J.; Gale, Nina; Franchi, Alessandro (eds.). Pathology of the Head and Neck. Springer. p. 737. ISBN 978-3-662-49670-1. 14. ^ Berg, Dale; Worzala, Katherine (2006). "3. Female genitourinary examination". Atlas of Adult Physical Diagnosis. Lippincott Williams & Wilkins. p. 55. ISBN 978-0-7817-4190-3. 15. ^ "New York Thyroid Center: Thyroid Nodules". Archived from the original on 2010-09-17. 16. ^ Ost D, Fein AM, Feinsilver SH; Fein; Feinsilver (June 2003). "Clinical practice. The solitary pulmonary nodule". New England Journal of Medicine. 348 (25): 2535–42. doi:10.1056/NEJMcp012290. PMID 12815140.CS1 maint: multiple names: authors list (link) ## External links[edit] * Diseases Database (DDB): 29379 * v * t * e Overview of tumors, cancer and oncology Conditions Benign tumors * Hyperplasia * Cyst * Pseudocyst * Hamartoma Malignant progression * Dysplasia * Carcinoma in situ * Cancer * Metastasis * Primary tumor * Sentinel lymph node Topography * Head and neck (oral, nasopharyngeal) * Digestive system * Respiratory system * Bone * Skin * Blood * Urogenital * Nervous system * Endocrine system Histology * Carcinoma * Sarcoma * Blastoma * Papilloma * Adenoma Other * Precancerous condition * Paraneoplastic syndrome Staging/grading * TNM * Ann Arbor * Prostate cancer staging * Gleason grading system * Dukes classification Carcinogenesis * Cancer cell * Carcinogen * Tumor suppressor genes/oncogenes * Clonally transmissible cancer * Oncovirus * Carcinogenic bacteria Misc. * Research * Index of oncology articles * History * Cancer pain * Cancer and nausea [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nodule (medicine)	None	30,040	wikipedia	https://en.wikipedia.org/wiki/Nodule_(medicine)	2021-01-18T18:31:42	{"wikidata": ["Q582484"]}
Parasitic disease Other namesparasitosis, parasitic infection False-color electron micrograph of a Plasmodium sporozoite. SpecialtyInfectious disease A parasitic disease, also known as parasitosis, is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases as it may eventually lead to death of both organism and host. Parasites infecting human beings are called human parasites. Parasitic diseases can affect practically all living organisms, including plants and mammals. The study of parasitic diseases is called parasitology. Some parasites like Toxoplasma gondii and Plasmodium spp. can cause disease directly, but other organisms can cause disease by the toxins that they produce.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatment * 4 Terminology * 5 References * 6 External links ## Signs and symptoms[edit] Symptoms of parasites may not always be obvious. However, such symptoms may mimic anemia or a hormone deficiency.[2] Some of the symptoms caused by several worm infestations can include itching affecting the anus or the vaginal area, abdominal pain, weight loss, increased appetite, bowel obstructions, diarrhea, and vomiting eventually leading to dehydration, sleeping problems, worms present in the vomit or stools, anemia, aching muscles or joints, general malaise, allergies, fatigue, and nervousness. Symptoms may also be confused with pneumonia or food poisoning.[3] The effects caused by parasitic diseases range from mild discomfort to death. The nematode parasites Necator americanus and Ancylostoma duodenale cause human hookworm infection, which leads to anaemia, protein malnutrition and, in severely malnourished people, shortness of breath and weakness.[4] This infection affects approximately 740 million people in the developing countries, including children and adults, of the tropics specifically in poor rural areas located in sub-Saharan Africa, Latin America, Southeast Asia and China.[citation needed] Chronic hookworm in children leads to impaired physical and intellectual development, school performance and attendance are reduced. Pregnant women affected by a hookworm infection can also develop anemia, which results in negative outcomes both for the mother and the infant. Some of them are: low birth weight, impaired milk production, as well as increased risk of death for the mother and the baby.[5] ## Causes[edit] See also: List of human parasitic diseases Mammals can get parasites from contaminated food or water, bug bites, or sexual contact. Ingestion of contaminated water can produce Giardia infections.[6] Parasites normally enter the body through the skin or mouth. Close contact with pets can lead to parasite infestation as dogs and cats are host to many parasites. Other risks that can lead people to acquire parasites are walking with barefeet, inadequate disposal of feces, lack of hygiene, close contact with someone carrying specific parasites, and eating undercooked foods, unwashed fruits and vegetables or foods from contaminated regions. Parasites can also be transferred to their host by the bite of an insect vector, i.e. mosquito, bed bug, fleas. ## Treatment[edit] Parasitic infections can usually be treated with antiparasitic drugs. Albendazole and mebendazole have been the treatments administered to entire populations to control hookworm infection. However, it is a costly option and both children and adults become reinfected within a few months after deparasitation occurs, raising concerns because the treatment has to repeatedly be administered and drug resistance may occur.[7] Another medication administered to kill worm infections has been pyrantel pamoate. For some parasitic diseases, there is no treatment and, in the case of serious symptoms, medication intended to kill the parasite is administered, whereas, in other cases, symptom relief options are used.[8] Recent papers have also proposed the use of viruses to treat infections caused by protozoa.[9][10] ## Terminology[edit] Although organisms such as bacteria function as parasites, the usage of the term "parasitic disease" is usually more restricted. The three main types of organisms causing these conditions are protozoa (causing protozoan infection), helminths (helminthiasis), and ectoparasites.[11] Protozoa and helminths are usually endoparasites (usually living inside the body of the host), while ectoparasites usually live on the surface of the host. Protozoa are single-celled, microscopic organisms that belong to the kingdom Protista.[12] Helminths on the other hand are macroscopic, multicellular organisms that belong to the kingdom Animalia.[12] Protozoans obtain their required nutrients through pinocytosis and phagocytosis.[12] Helminths of class Cestoidea and Trematoda absorb nutrients, whereas nematodes obtain needed nourishment through ingestion.[12] Occasionally the definition of "parasitic disease" is restricted to diseases due to endoparasites.[13] ## References[edit] 1. ^ Jones D, Wache S, Chhokar V (1996). "Toxins produced by arthropod parasites: salivary gland proteins of human body lice and venom proteins of chelonine wasps". Toxicon. 34 (11–12): 1421–9. doi:10.1016/s0041-0101(96)00091-8. PMID 9027999. 2. ^ "Parasite Infection and Parasite Treatment". Retrieved 2010-07-07. 3. ^ "Parasitic Diseases". Retrieved 2010-07-07. 4. ^ Harrison's manual of medicine. Harrison, Tinsley Randolph, 1900-1978., Kasper, Dennis L.,, Longo, Dan L. (Dan Louis), 1949-, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Jameson, J. Larry (19th ed.). New York. 2016-05-22. ISBN 9780071828543. OCLC 930026813.CS1 maint: others (link) 5. ^ "Hookworm disease". Retrieved 2010-07-07. 6. ^ "Parasitic Diseases". Retrieved 2010-07-07. 7. ^ "Disease Burden". Retrieved 2010-07-07. 8. ^ "Parasitic diseases". Retrieved 2010-07-07. 9. ^ Keen, E. C. (2013). "Beyond phage therapy: Virotherapy of protozoal diseases". Future Microbiology. 8 (7): 821–823. doi:10.2217/FMB.13.48. PMID 23841627. 10. ^ Hyman, P.; Atterbury, R.; Barrow, P. (2013). "Fleas and smaller fleas: Virotherapy for parasite infections". Trends in Microbiology. 21 (5): 215–220. doi:10.1016/j.tim.2013.02.006. PMID 23540830. 11. ^ "About Parasites \| CDC DPD". 2020-01-28. 12. ^ a b c d Sherris medical microbiology. Ryan, Kenneth J. (Kenneth James), 1940- (Seventh ed.). New York. 2018-01-12. ISBN 9781259859816. OCLC 1004770160.CS1 maint: others (link) 13. ^ "Intestinal Protozoal Diseases: eMedicine Pediatrics: General Medicine". Retrieved 2010-04-25. ## External links[edit] Classification D * MeSH: D010272 * v * t * e Amoebozoal diseases Lobosea (free-living) Centramoebida * Acanthamoeba * Acanthamoeba keratitis * Cutaneous acanthamoebiasis * Granulomatous amoebic encephalitis * Acanthamoeba infection * Balamuthia mandrillaris * Balamuthia amoebic encephalitis * Balamuthia infection Flabellinia * Sappinia diploidea/Sappinia pedata * Sappinia amoebic encephalitis Conosa/Archamoebae * Entamoeba histolytica * Amoebiasis * Amoebic dysentery * Amoebic liver abscess * Cutaneous amoebiasis * Amoebic brain abscess * Amebiasis cutis * Entamoeba gingivalis * v * t * e Parasitic disease caused by Excavata protozoa Discicristata Trypanosomatida Trypanosomiasis * T. brucei * African trypanosomiasis * T. cruzi * Chagas disease Leishmaniasis * Leishmania major / L. mexicana / L. aethiopica / L. tropica * Cutaneous leishmaniasis * L. braziliensis * Mucocutaneous leishmaniasis * L. donovani / infantum * Visceral leishmaniasis Schizopyrenida * Naegleria fowleri * Primary amoebic meningoencephalitis Trichozoa Diplomonadida * Giardia lamblia (Giardiasis) Trichomonadida * Trichomonas vaginalis * Trichomoniasis * Dientamoeba fragilis * Dientamoebiasis * v * t * e Protozoan infection: SAR and Archaeplastida SAR Alveolate Apicomplexa Conoidasida/ Coccidia * Coccidia: Cryptosporidium hominis/Cryptosporidium parvum * Cryptosporidiosis * Cystoisospora belli * Isosporiasis * Cyclospora cayetanensis * Cyclosporiasis * Toxoplasma gondii * Toxoplasmosis Aconoidasida * Plasmodium falciparum/vivax/ovale/malariae/knowlesi * Malaria * Blackwater fever * Babesia * Babesiosis Ciliophora * Balantidium coli * Balantidiasis Heterokont * Blastocystis * Blastocystosis * Pythium insidiosum * Pythiosis Archaeplastida * Algaemia: Prototheca wickerhamii * Protothecosis * v * t * e Parasitic disease caused by helminthiases Flatworm/ platyhelminth infection Fluke/trematode (Trematode infection) Blood fluke * Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum * Schistosomiasis * Trichobilharzia regenti * Swimmer's itch Liver fluke * Clonorchis sinensis * Clonorchiasis * Dicrocoelium dendriticum / D. hospes * Dicrocoeliasis * Fasciola hepatica / F. gigantica * Fasciolosis * Opisthorchis viverrini / O. felineus * Opisthorchiasis Lung fluke * Paragonimus westermani / P. kellicotti * Paragonimiasis Intestinal fluke * Fasciolopsis buski * Fasciolopsiasis * Metagonimus yokogawai * Metagonimiasis * Heterophyes heterophyes * Heterophyiasis Cestoda (Tapeworm infection) Cyclophyllidea * Echinococcus granulosus / E. multilocularis * Echinococcosis * Taenia saginata / T. asiatica / T. solium (pork) * Taeniasis / Cysticercosis * Hymenolepis nana / H. diminuta * Hymenolepiasis Pseudophyllidea * Diphyllobothrium latum * Diphyllobothriasis * Spirometra erinaceieuropaei * Sparganosis * Diphyllobothrium mansonoides * Sparganosis Roundworm/ Nematode infection Secernentea Spiruria Camallanida * Dracunculus medinensis * Dracunculiasis Spirurida Filarioidea (Filariasis) * Onchocerca volvulus * Onchocerciasis * Loa loa * Loa loa filariasis * Mansonella * Mansonelliasis * Dirofilaria repens * D. immitis * Dirofilariasis * Wuchereria bancrofti / Brugia malayi / \|B. timori * Lymphatic filariasis Thelazioidea * Gnathostoma spinigerum / G. hispidum * Gnathostomiasis * Thelazia * Thelaziasis Spiruroidea * Gongylonema Strongylida (hookworm) * Hookworm infection * Ancylostoma duodenale / A. braziliense * Ancylostomiasis / Cutaneous larva migrans * Necator americanus * Necatoriasis * Angiostrongylus cantonensis * Angiostrongyliasis * Metastrongylus * Metastrongylosis Ascaridida * Ascaris lumbricoides * Ascariasis * Anisakis * Anisakiasis * Toxocara canis / T. cati * Visceral larva migrans / Toxocariasis * Baylisascaris * Dioctophyme renale * Dioctophymosis * Parascaris equorum Rhabditida * Strongyloides stercoralis * Strongyloidiasis * Trichostrongylus spp. * Trichostrongyliasis * Halicephalobus gingivalis Oxyurida * Enterobius vermicularis * Enterobiasis Adenophorea * Trichinella spiralis * Trichinosis * Trichuris trichiura (Trichuriasis / Whipworm) * Capillaria philippinensis * Intestinal capillariasis * C. hepatica * v * t * e Arthropods and ectoparasite-borne diseases and infestations Insecta Louse * Body louse (pediculosis corporis) / Head louse (head lice infestation) * Crab louse (phthiriasis) Hemiptera * Bed bug (cimicosis) Fly * Dermatobia hominis / Cordylobia anthropophaga / Cochliomyia hominivorax (myiasis) * Mosquito (mosquito-borne disease) Flea * Tunga penetrans (tungiasis) Crustacea Pentastomida * Linguatula serrata (linguatulosis) * Porocephalus crotali / Armillifer armillatus (porocephaliasis) * For ticks and mites, see Template:Tick and mite-borne diseases and infestations Authority control * NDL: 00565989 * Medicine portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Parasitic disease	c0014238	30,041	wikipedia	https://en.wikipedia.org/wiki/Parasitic_disease	2021-01-18T18:51:59	{"mesh": ["D010272"], "umls": ["C0014238"], "icd-10": ["B89"], "orphanet": ["163588"], "wikidata": ["Q1601794"]}
Crigler-Najjar syndrome type 2 (CN-2) is a rare disorder that causes elevated levels of bilirubin in the blood (hyperbilirubinemia). Bilirubin normally is made by the body when old red blood cells are broken down. However, people with CN-2 develop hyperbilirubinemia even when red blood cells are not excessively broken down, because they have too little of a liver enzyme needed for conversion and excretion of bilirubin. The main symptom of CN-2 is persistent jaundice, which is yellowing of the skin, mucous membranes and whites of the eyes. Jaundice may become noticeable in infancy (particularly when an infant is sick or has not eaten for an extended time), but some people with CN-2 are not diagnosed until adulthood. Rarely, a person with CN-2 may develop bilirubin encephalopathy (also called kernicterus), especially during illness, prolonged fasting, or while under anesthesia. CN-2 is caused by mutations in the UGT1A1 gene and inheritance is autosomal recessive. CN-2 responds to treatment with phenobarbital; however during an episode of severe hyperbilirubinemia, phototherapy may be needed. Not all people with CN-2 require treatment, but routine monitoring is still recommended. Of note, mutations in the UGT1A1 gene can alternatively cause other disorders, such as Crigler-Najjar syndrome type 1 (CN-1) and Gilbert syndrome. CN-1 is characterized by near or complete absence of enzyme activity (versus partial absence in type 2) and severe, life-threatening symptoms. Phenobarbitol treatment is ineffective for people with CN-1, which is treated differently. Gilbert syndrome is considered a mild liver disorder that often does not cause symptoms or causes mild jaundice. Sometimes it can be hard to distinguish between Gilbert syndrome and CN-2 because of considerable overlap in measured bilirubin levels. Genetic testing to identify the specific mutation present is sometimes needed for the correct diagnosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Crigler-Najjar syndrome type 2	c2931132	30,042	gard	https://rarediseases.info.nih.gov/diseases/8683/crigler-najjar-syndrome-type-2	2021-01-18T18:01:02	{"mesh": ["C536213"], "omim": ["606785"], "umls": ["C2931132"], "orphanet": ["79235"], "synonyms": ["Crigler-Najjar syndrome, type II", "Crigler Najjar syndrome type 2", "Arias syndrome"]}
human disease characterized by an overgrowth of skin, bones, muscles, fatty tissues, and blood and lymphatic vessels Proteus syndrome Other namesPartial gigantism-nevi-hemihypertrophy-macrocephaly syndrome, Wiedemann syndrome A 7-year-old boy with Proteus syndrome, confirmed to have the AKT1 p.E17K somatic variant SpecialtyMedical genetics Proteus syndrome is a rare disorder with a genetic background[1] that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development.[2] The clinical and radiographic manifestations of Proteus syndrome are highly variable. Yet, the orthopedic manifestations of the syndrome are unique.[3][4] The syndrome is named after the Greek sea-god Proteus, who could change his shape. The condition appears to have been first described in the American medical literature by Samia Temtamy and John Rogers in 1976.[5][6] Michael Cohen described it in 1979.[7] Only a few more than 200 cases have been confirmed worldwide, with estimates that about 120 people are currently alive with the condition.[8] As attenuated forms of the disease may exist, there could be many people with Proteus syndrome who remain undiagnosed. Those most readily diagnosed are also the most severely disfigured. ## Contents * 1 Signs and symptoms * 1.1 Orthopaedic features * 2 Genetics * 3 Diagnosis * 3.1 Differential diagnosis * 3.2 Classification * 4 Treatment * 5 Notable cases * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Proteus syndrome causes an overgrowth of skin, bones, muscles, fatty tissues, and blood and lymphatic vessels. Proteus syndrome is a progressive condition wherein children are usually born without any obvious deformities. Tumors of skin and bone growths appear as they age typically in early childhood. The musculoskeletal manifestations are cardinal for the diagnosis of Proteus syndrome.[3] The severity and locations of these various asymmetrical growths vary greatly but typically the skull, one or more limbs, and soles of the feet will be affected. There is a risk of premature death in affected individuals due to deep vein thrombosis and pulmonary embolism caused by the vessel malformations that are associated with this disorder. Because of carrying excess weight and enlarged limbs, arthritis and muscle pain may also be symptoms. Further risks may occur due to the mass of extra tissue.[citation needed] The disorder itself does not uniformly cause learning impairments: the distribution of intelligence deficits among sufferers of Proteus syndrome appears higher than that of the general population, although this is difficult to determine with statistical significance.[9] In addition, the presence of visible deformity may have a negative effect on the social experiences of the affected individual, causing cognitive and social deficits.[citation needed] Afflicted individuals are at increased risk for developing certain tumors including unilateral ovarian cystadenomas, testicular tumors, meningiomas, and monomorphic adenomas of the parotid gland.[citation needed] Hemimegalencephaly is often found to be associated.[10] ### Orthopaedic features[edit] The musculoskeletal manifestations of Proteus syndrome are frequent and recognizable. Patients tend to demonstrate a unique pattern of skeletal abnormalities. The orthopaedic features are usually bilateral, asymmetrical, progressive and involving all four limbs and spine. Afflicted patients usually have localized periarticular limb distortions, limb length discrepancy, and spine deformity. Patients with Proteus syndrome can have regular bone configuration and contours despite the bone enlargement.[3] Patients can also exhibit deformation of the skull in the form of dolichocephaly or elongated skull and facial abnormalities. Because of the rarity of the syndrome and the variability of signs, the orthopaedic management should be individualized.[3] ## Genetics[edit] Proteus syndrome is an overgrowth disorder caused by a rare genetic mosaicism. A genetic mutation during embryonic development gives rise to overgrowth in a subset of the individual's cells In 2011 researchers determined the cause of Proteus syndrome. In 26 of 29 patients who met strict clinical criteria for the disorder, Lindhurst et al. identified an activating mutation in AKT1 kinase in a mosaic state gene.[11] Previous research had suggested the condition linked to PTEN on chromosome 10,[12] while other research pointed to chromosome 16.[13] Prior to the findings regarding AKT1 in 2011, other researchers expressed doubt regarding the involvement of PTEN or GPC3, which codes for glypican 3 and may play a role in regulating cell division and growth regulation.[14][15] ## Diagnosis[edit] ### Differential diagnosis[edit] * Macrodystrophia lipomatosa[16] * Fibrolipomatous hamartoma * Neurofibromatosis type 1.[17] * Klippel Trenaunay syndrome.[18] * Parkes Weber syndrome * Sotos syndrome * Hemangiomas.[19] ### Classification[edit] Many sources classify Proteus syndrome to be a type of nevus syndrome. The lesions appear to be distributed in a mosaic manner.[20] It has been confirmed that the disorder is an example of genetic mosaicism.[11] ## Treatment[edit] A team of doctors in Australia have trial tested the drug rapamycin in the treatment of a patient said to have Proteus syndrome and have found it to be an effective remedy.[21] However, the diagnosis of Proteus syndrome in this patient has been questioned by others.[22] The Proteus syndrome research team in the National Human Genome Research Institute at the United States National Institutes of Health have initiated a Phase 0 dose finding trial with the AKT1 inhibitor ARQ 092, which is being developed by the Arqule Corporation. In earlier tests on tissue and cell samples obtained from patients, ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in as little as two hours.[23] The Phase 0 trial opened in November 2015 and recruited patients in a study titled "Dose Finding Trial of ARQ 092 in Children and Adults With Proteus Syndrome"[24] This trial is based on in vitro data showing inhibition of AKT1 in cell lines from patients with Proteus syndrome.[25] ## Notable cases[edit] In a 1986 article in the British Medical Journal, Michael Cohen and J.A.R. Tibbles put forward the theory that Joseph Merrick (an Englishman known as the "Elephant Man") had suffered from Proteus syndrome. However, the exact condition suffered by Joseph Merrick is still not known with certainty.[26][27] Mandy Sellars has been diagnosed by some doctors as suffering from this condition.[8] Her legs and feet have grown at a disproportionate rate since birth. However, in 2013, Sellars' case was profiled on British television in a special called Shrinking My 17 Stone Legs, in which it was determined that Sellars' condition was not, in fact, Proteus syndrome, but rather the often-misdiagnosed PIK3CA-related overgrowth spectrum, a syndrome caused by a PIK3CA gene mutation.[citation needed] ## See also[edit] * Epidermal nevus syndrome * Mosaic (genetics) * List of radiographic findings associated with cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 554. ISBN 978-0-7216-2921-6. 2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 3. ^ a b c d El-Sobky, Tamer Ahmed; Elsayed, Solaf M.; El Mikkawy, Dalia M.E. (2015). "Orthopaedic manifestations of Proteus syndrome in a child with literature update". Bone Reports. 3: 104–108. doi:10.1016/j.bonr.2015.09.004. PMC 5365241. PMID 28377973. 4. ^ Jamis-Dow CA, Turner J, Biesecker LG, Choyke PL (2004). "Radiologic manifestations of Proteus syndrome". Radiographics. 24 (4): 1051–68. doi:10.1148/rg.244035726. PMID 15256628. 5. ^ Temtamy SA, Rogers JG (December 1976). "Macrodactyly, hemihypertrophy, and connective tissue nevi: Report of a new syndrome and review of the literature". The Journal of Pediatrics. 89 (6): 924–927. doi:10.1016/S0022-3476(76)80597-5. PMID 993918. 6. ^ Opitz JM, Jorde LB (July 27, 2011). "Hamartoma Syndromes, Exome Sequencing, and a Protean Puzzle". The New England Journal of Medicine. 365 (7): 661–3. doi:10.1056/NEJMe1107384. PMID 21793737. 7. ^ Cohen MM, Hayden PW (1979). "A newly recognized hamartomatous syndrome". Birth Defects Orig. Artic. Ser. 15 (5B): 291–6. PMID 118782. 8. ^ a b Woman's 11-stone legs may be lost at BBC 9. ^ Turner JT, Cohen MM, Biesecker LG (Oct 1, 2004). "Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases". American Journal of Medical Genetics. 130A (2): 111–122. doi:10.1002/ajmg.a.30327. PMID 15372514. S2CID 41588085. 10. ^ Bastos, Halisson; da Silva, Paula Fabiana Sobral; de Albuquerque, Marco Antônio Veloso; Mattos, Adriana; Riesgo, Rudimar Santos; Ohlweiler, Lygia; Winckler, Maria Isabel Bragatti; Bragatti, José Augusto; Duarte, Rodrigo Dias; Zandoná, Denise Isabel (June 2008). "Proteus syndrome associated with hemimegalencephaly and Ohtahara syndrome: Report of two cases". Seizure. 17 (4): 378–382. doi:10.1016/j.seizure.2007.11.001. PMID 18082431. S2CID 13492116. 11. ^ a b Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (Aug 18, 2011). "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N Engl J Med. 365 (7): 611–9. doi:10.1056/NEJMoa1104017. PMC 3170413. PMID 21793738. 12. ^ Smith JM, Kirk EP, Theodosopoulos G, Marshall GM, Walker J, Rogers M, Field M, Brereton JJ, Marsh DJ (2002). "Germline mutation of the tumour suppressor PTEN in Proteus syndrome". J. Med. Genet. 39 (12): 937–40. doi:10.1136/jmg.39.12.937. PMC 1757209. PMID 12471211. 13. ^ Cardoso MT, de Carvalho TB, Casulari LA, Ferrari I (2003). "Proteus syndrome and somatic mosaicism of the chromosome 16". Panminerva Medica. 45 (4): 267–71. PMID 15206168. 14. ^ Thiffault I, Schwartz CE, Der Kaloustian V, Foulkes WD (October 2004). "Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome". Am. J. Med. Genet. A. 130A (2): 123–7. doi:10.1002/ajmg.a.30335. PMID 15372512. S2CID 32014732. 15. ^ "Entrez Gene: GPC3 glypican 3". 16. ^ Abdulhady, H; El-Sobky, TA; Elsayed, NS; Sakr, HM (11 June 2018). "Clinical and imaging features of pedal macrodystrophia lipomatosa in two children with differential diagnosis review". Journal of Musculoskeletal Surgery and Research. 2 (3): 130. doi:10.4103/jmsr.jmsr_8_18. S2CID 80970016. 17. ^ Friedman, JM (11 January 2018). Neurofibromatosis 1. GeneReviews. University of Washington, Seattle. Retrieved 30 April 2018. 18. ^ Sung, HM; Chung, HY; Lee, SJ; et, al (2015). "Clinical experience of the Klippel-Trenaunay syndrome". Arch Plast Surg. 42 (5): 552–8. doi:10.5999/aps.2015.42.5.552. PMC 4579165. PMID 26430625. 19. ^ Nguyen, TA; Krakowski, AC; Naheedy, JH; Kruk, PG; Friedlander, SF (2015). "Imaging Pediatric Vascular Lesions". Clin Aesthet Dermatol. 8 (12): 27–41. PMC 4689509. PMID 26705446. 20. ^ Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM, Viljoen DL, Cohen MM (1999). "Proteus syndrome: differential diagnosis, and patient evaluation". Am J Med Genet. 84 (5): 389–95. doi:10.1002/(SICI)1096-8628(19990611)84:5<389::AID-AJMG1>3.0.CO;2-O. PMID 10360391. 21. ^ Marsh DJ, Trahair TN, Martin JL, Chee WY, Walker J, Kirk EP, Baxter RC, Marshall GM (April 22, 2008). "Rapamycin treatment for a child with germline PTEN mutation". Nature Clinical Practice Oncology. 5 (6): 357–361. doi:10.1038/ncponc1112. PMID 18431376. S2CID 2870300. 22. ^ Cohen MM, Turner JT, Biesecker LG (November 1, 2003). "Proteus Syndrome: Misdiagnosis with PTEN Mutations". American Journal of Medical Genetics. 122A (4): 323–324. doi:10.1002/ajmg.a.20474. PMID 14518070. S2CID 26811086. 23. ^ Lindhurst, Marjorie J.; Yourick, Miranda R.; Yu, Yi; Savage, Ronald E.; Ferrari, Dora; Biesecker, Leslie G. (2015-12-11). "Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome". Scientific Reports. 5: 17162. Bibcode:2015NatSR...517162L. doi:10.1038/srep17162. ISSN 2045-2322. PMC 4675973. PMID 26657992. 24. ^ "Dose Finding Trial of ARQ 092 in Children and Adults With Proteus Syndrome". ClinicalTrials.gov. National Human Genome Research Institute (NHGRI). Oct 31, 2015. NCT02594215. 25. ^ Lindhurst, Marjorie J.; Yourick, Miranda R.; Yu, Yi; Savage, Ronald E.; Ferrari, Dora; Biesecker, Leslie G. (2015). "Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome". Scientific Reports. 5: 17162. Bibcode:2015NatSR...517162L. doi:10.1038/srep17162. PMC 4675973. PMID 26657992. 17162. 26. ^ Tibbles JA, Cohen MM (1986). "The Proteus syndrome: the Elephant Man diagnosed". Br Med J (Clin Res Ed). 293 (6548): 683–5. doi:10.1136/bmj.293.6548.683. PMC 1341524. PMID 3092979. 27. ^ – Spiring P (2001). "The Improbable Elephant Man". Biologist (London) 48(3) 104., Article in The Sunday Telegraph, – BBC News, [http://www.eurekalert.org/pub_releases/2003-07/dhc-ada071803.php – Eurekalert!, Article in The Daily Telegraph ## External links[edit] Classification D * OMIM: 176920 * MeSH: D016715 * DiseasesDB: 30070 External resources * eMedicine: derm/721 ped/1912 * Orphanet: 744 * GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS) * v * t * e Phakomatosis Angiomatosis * Sturge–Weber syndrome * Von Hippel–Lindau disease Hamartoma * Tuberous sclerosis * Hypothalamic hamartoma (Pallister–Hall syndrome) * Multiple hamartoma syndrome * Proteus syndrome * Cowden syndrome * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease Neurofibromatosis * Type I * Type II Other * Abdallat–Davis–Farrage syndrome * Ataxia telangiectasia * Incontinentia pigmenti * Peutz–Jeghers syndrome * Encephalocraniocutaneous lipomatosis * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Proteus syndrome	c1867610	30,043	wikipedia	https://en.wikipedia.org/wiki/Proteus_syndrome	2021-01-18T18:39:16	{"gard": ["7475"], "mesh": ["C537716", "D016715"], "umls": ["C1867610"], "orphanet": ["744"], "wikidata": ["Q281115"]}
Kyphomelic dysplasia is a prenatal skeletal disease that causes dwarfism characterized by the following: a disproportionately short stature with a short narrow chest, shortening and bending (bowing) of the limbs, flared irregular metaphyses of the bones, and characteristic facial features. Bone changes are said to improve with age. Kyphomelic dysplasia is inherited in an autosomal recessive pattern. Recent studies indicate that Kyphomelic dysplasia is no longer considered it's own entity and that individual cases should be further evaluated and re-classified as another existing chondrodysplasias, such as Schwartz-Jampel syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Kyphomelic dysplasia	c0432239	30,044	gard	https://rarediseases.info.nih.gov/diseases/10149/kyphomelic-dysplasia	2021-01-18T17:59:33	{"mesh": ["C538128"], "omim": ["211350"], "umls": ["C0432239"], "orphanet": ["1801"], "synonyms": ["Bowing, congenital, with short bones", "Congenital bowing with short bones"]}
A number sign (#) is used with this entry because of evidence that proteasome-associated autoinflammatory syndrome-1 (PRAAS1) is caused by homozygous mutation in the PSMB8 gene (177046) on chromosome 6p21. Digenic forms of PRAAS1 can be caused by heterozygous mutation in the PSMB8 gene and heterozygous mutation in either the PSMA3 (176843) gene on chromosome 14q23 or in the PSMB4 (602177) on chromosome 1q21. Description This autosomal recessive systemic autoinflammatory disorder is characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. ### Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12, and PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21. Clinical Features Nakajo (1939) described 2 sibs, born of consanguineous parents, with nodular erythema, elongated and thickened fingers, and emaciation. He called the disorder 'secondary hypertrophic osteoperiostosis with pernio.' Both sibs had cardiomegaly and cardiac insufficiency. Nakajo (1939) thought the changes in the fingers were due to cardiac disease. Nishimura et al. (1950) reported 3 Japanese patients from 2 families with hypertrophic pulmonary osteoarthropathy with pernio-like skin eruptions. Kitano et al. (1985) found a total of 12 cases including 4 of their own in the Japanese literature. No cases had been reported in Caucasians at that time. The 12 cases were distributed in 8 kindreds, most of which were consanguineous. Other features included large eyes, nose, lips and ears, disproportionately long and thick fingers, and loss of adipose tissue in the upper part of the body. Yamada et al. (1984) and Tanaka et al. (1993) reported a Japanese brother and sister, born of consanguineous parents, with childhood onset of systemic joint pain and severe deformities of the fingers as well as recurrent skin eruptions followed by progressive loss of fat in the upper and then the lower extremities. The skin eruptions were similar to erythema nodosum, were associated with fever, and were steroid-responsive. The patients also had muscle atrophy and weakness in the areas of lipodystrophy, which resulted in the inability to walk in 1 patient by age 44 years and in the other at age 35 years. Other features included mild mental retardation, hepatomegaly, macroglossia, and extensor plantar responses. Laboratory study of the sister at age 44 years showed increased erythrocyte sedimentation rate (ESR), hypergammaglobulinemia, and impaired glucose tolerance. Brain CT scan showed calcification of the basal ganglia. Oyanagi et al. (1987) provided follow-up of the brother reported by Yamada et al. (1984) who had died of heart failure at age 47 years after developing cardiac arrhythmias at age 39. Postmortem examination showed severely atrophic skeletal muscles with fibrosis apparent on microscopic examination. There were rimmed vacuoles and lobulated fibers. Electron microscopy showed myofibrillary necrosis, Z-disc streaming, and intramitochondrial paracrystalline inclusions. These changes were considered to be indicative of ischemia. Similar, but less severe, findings were observed in the tongue, extraocular muscles, and heart. Blood vessels in skeletal muscle showed hyperplasia of the media with and narrowing and obstruction of the lumen. Small vessels showed hypertrophy of endothelial cells, whereas arterioles showed hyperplasia of smooth muscle cells with hypertrophy of endothelial cells and some degeneration of endothelial cells. The heart was hypertrophic, with patchy calcification of some vessels. There were also some calcium deposits in vessels of the basal ganglia. Tanaka et al. (1993) noted that 13 other Japanese patients with similar clinical manifestations had been reported, suggesting a distinct clinical entity. Kitamura et al. (2011) provided clinical details of 3 Japanese patients with Nakajo syndrome, including the patients reported by Tanaka et al. (1993). Patients presented with recurrent high fever with nodular erythema between 1 month and 3 years of age, and began to develop partial lipodystrophy between 6 and 12 years of age. Lipodystrophy was particularly prominent in the face, fingers, and upper limbs. Other features included muscle weakness, deformities of the hands, and frostbitten hands. Laboratory studies showed increased serum C-reactive protein, IgG, and IgA, but autoantibodies were not detected. Arima et al. (2011) reported 7 patients with the disorder, including the patient reported by Oyanagi et al. (1987). Clinical features included thin facial appearance, partial lipomuscular atrophy, and long clubbed fingers. All had a pernio-like, heliotrope-like, or nodular erythema-like skin rash, and most had periodic fever and joint contractures. All had evidence of chronic inflammation, as indicated by elevated ESR and hypergammaglobulinemia. Most had microcytic anemia, hepatosplenomegaly, and basal ganglia calcification. More variable features included hyperhidrosis and short stature; only 1 had low IQ. About half of patients had various autoantibodies. Garg et al. (2010) reported a Portuguese man and 2 Mexican sibs with what they termed JMP syndrome, for joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy. All had marked generalized lipodystrophy with a progeroid appearance and severe joint contractures of the elbows, hands, fingers, feet, and toes. Onset of lipodystrophy appeared in childhood, after appearance of erythematous nodular skin lesions. Skin biopsy of the skin lesions from 1 patient showed panniculitis. All patients had short stature and muscle atrophy and weakness. Other features included dry, stiff skin, hepatosplenomegaly, microcytic anemia, and hypergammaglobulinemia. Two had mild hypertriglyceridemia, and all 3 had low HDL cholesterol. The Mexican sibs both had seizures, but none of the patients had mental retardation. Garg et al. (2010) noted the phenotypic similarities to the Japanese patients reported by Tanaka et al. (1993), and postulated an autoinflammatory disorder. Laboratory studies of the 2 Mexican sibs performed by Agarwal et al. (2010) showed that both had significantly increased levels of serum IL6 (147620) and gamma-interferon (IFNG; 147570), and 1 had increased IL8 (146930). Other cytokines were not elevated, suggesting a particular biomarker signature. Arima et al. (2011) asserted that the most striking differences between NJKO and JMP (Garg et al., 2010) were the absence of fever in JMP syndrome and the absence of seizures in NJKO. Torrelo et al. (2010) reported 4 patients, including 2 sibs, with an autoinflammatory disorder characterized by onset in infancy of recurrent fever, annular erythematous skin lesions, persistent violaceous eyelid swelling, poor overall growth, partial lipodystrophy, hepatomegaly, and arthralgias. Laboratory studies showed increased erythrocyte sedimentation rate, C-reactive protein, and hypochromic anemia. All also had intermittent elevated liver enzymes. Two patients had hypertriglyceridemia, 2 had increased platelet counts, and 2 had basal ganglia calcifications. Histologic analysis of skin lesions showed atypical mononuclear infiltrates and mature neutrophils. Torrelo et al. (2010) proposed the acronym chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE) to refer to this presumably autosomal recessive disorder. In 3 of the patients reported by Torrelo et al. (2010), Liu et al. (2012) identified the same homozygous mutation in the PSMB8 gene (T75M; 177046.0001); the fourth patient, who had died at age 14 years, was presumed to carry the same mutation as her sister. ### Digenic Inheritance Brehm et al. (2015) reported 2 brothers (patients 6 and 7) of Irish descent (family 5) with digenic inheritance of PRAAS. The patients carried a heterozygous nonsense mutation in the PSMB4 gene (Y222X; 602177.0001) on 1 allele and a missense mutation in the PSMB8 gene (K105Q; 177046.0005) on the other allele. The patients presented in the first 3 to 4 weeks of life with skin lesions, fever, and anemia. They had annular plaques, violaceous eyelids, hyperpigmented macules, and scarring. Additional features included poor overall growth, lymphadenopathy, hepatosplenomegaly, myositis, arthritis/arthralgias, recurrent infections, joint contractures, and lipodystrophy. Laboratory studies showed elevated acute phase reactants, microcytic anemia, and lymphopenia. Both patients also had intracranial basal ganglia calcifications. One patient had autoantibodies. Brehm et al. (2015) also reported 2 additional unrelated patients (patients 2 and 3) with digenic PRAAS1. The patients had previously been reported as patients 7 and 9 by Liu et al. (2012), who identified a heterozygous missense mutation in the PRMB8 gene (T75M; 177046.0001) in both patients, but a second mutation could not be found. Using a combination of whole-exome sequencing and screening of proteasomal candidate genes in these patients, Brehm et al. (2015) found that these patients carried a heterozygous mutation in the PSMA3 gene (176843.0001 and 176843.0002, respectively) on 1 allele and the common heterozygous heterozygous T75M missense mutation in the PSMB8 gene on the other allele. The mutations segregated with the disorder in the families, although 1 of the patients had a de novo mutation in the PSMA3 gene. The patients had onset of symptoms in the first months of life. Features were somewhat variable, but included periorbital erythema and edema, violaceous eyelids, fever, skin lesions, myositis, arthralgia, joint contracture, increased acute phase reactants, lymphadenopathy, lipodystrophy, and poor overall growth. Laboratory studies showed thrombocytopenia, hypochromic anemia, lymphopenia, autoantibodies, lipid abnormalities, abnormal liver enzymes, increased acute phase reactants, and hypergammaglobulinemia. Inheritance The affected sibs reported by Tanaka et al. (1993) were born of consanguineous parents, indicating an autosomal recessive pattern of inheritance. Agarwal et al. (2010) confirmed consanguinity of the parents of the Portuguese patient reported by Garg et al. (2010). Molecular Genetics By genomewide homozygosity mapping followed by candidate gene sequencing of the 3 patients reported by Garg et al. (2010), Agarwal et al. (2010) identified the same homozygous mutation in the PSMB8 gene (T75M; 177046.0001). Studies of patient lymphocytes showed that the mutant protein had markedly decreased chymotrypsin-like activity compared to wildtype, consistent with a decrease in proteasomal activity and loss of function. The findings indicated that dysfunction of the immunoproteasome can result in an autoinflammatory disease. Kitamura et al. (2011) identified a homozygous PSMB8 mutation (G197V; 177046.0002) in 3 Japanese patients from 2 consanguineous families with Nakajo syndrome. One of the families had previously been reported by Tanaka et al. (1993). The mutation increased assembly intermediates of immunoproteasomes, resulting in decreased proteasome function and ubiquitin-coupled protein accumulation in patient tissues. In vitro studies showed that downregulation of PSMB8 inhibited the differentiation of murine and human adipocytes in vitro, and injection of siRNA against Psmb8 in mouse skin reduced adipocyte tissue volume. The findings indicated that PSMB8 has a role in both inflammation and adipocyte differentiation, explaining the pleiotropic feature of this disorder. In 5 unrelated Japanese patients with Nakajo-Nishimura syndrome, including 1 of the patients originally reported by Yamada et al. (1984), Arima et al. (2011) identified a homozygous mutation in the PSMB8 gene (G201V; 177046.0003). Haplotype analysis indicated a founder effect. Patient-derived lymphoblastoid cell lines showed markedly decreased chymotrypsin-like, trypsin-like, and caspase-like activity. Arima et al. (2011) noted that the T75M mutant protein reported by Garg et al. (2010) caused only diminished chymotrypsin-like activity, whereas other pepsidase activities remained normal, suggesting a possible biochemical basis for the slightly different phenotype reported by them (JMP syndrome). In 5 patients with CANDLE syndrome, Liu et al. (2012) identified homozygous mutations in the PSMB8 gene (177046.0001 and 177046.0004). Three of the patients (patients 1, 2, and 4) had previously been reported by Torrelo et al. (2010). The patients had high levels of gamma-interferon-induced protein-10 (CXCL10; 147310), as well as other inflammatory markers. Microarray profiling suggested dysregulation of the interferon signaling pathway, particularly gamma-interferon. Two additional patients (patients 7 and 9) were heterozygous for a PSMB8 T75M mutation, but a second pathogenic mutation could not be found. In 2 unrelated patients reported by Liu et al. (2012) (patients 7 and 9) with a heterozygous T75M PSMB8 mutation, Brehm et al. (2015) identified heterozygous mutations in the PSMA3 gene (176843.0001 and 176843.0002) on the other allele, consistent with digenic inheritance. Brehm et al. (2015) referred to the patients as patient 2 (American/Caucasian origin) and patient 3 (of Spanish origin). Two sibs from another family (family 5) carried a missense mutation in the PSMB8 gene (K105Q; 176843.0005) on 1 allele and a nonsense mutation in the PSMB4 gene (Y222X; 602177.0004) on the other allele, also consistent with digenic inheritance. Detailed functional studies, including in vitro studies of patient cells, expression of the mutations into HeLa cells, and siRNA-mediated knockdown of the PSMB4, PSMB3, and PSMB9 genes, demonstrated that the mutations resulted in variable defects in proteasome 20S and 26S assembly and maturation, with accumulation of proteasome precursor complexes, as well as impaired proteolytic activity. The defects were associated with induction of a type I interferon response with strong expression of IFN-inducible genes and an increase in chemokines and cytokines. Brehm et al. (2015) concluded that mutations in proteasomal subunit genes adversely affect proteasomal function, leading to cell stress and the triggering of a type I IFN gene response, causing a vicious cycle of uncontrolled inflammation in both hematopoietic and nonhematopoietic cells. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (less common) Other \- Failure to thrive \- Poor growth HEAD & NECK Face \- Loss of facial subcutaneous fat \- Periorbital swelling due to violaceous plaques on the eyelids Eyes \- Conjunctivitis \- Episcleritis Mouth \- Macroglossia \- Thick lips CARDIOVASCULAR Heart \- Cardiac insufficiency (in some) \- Arrhythmias (in some) ABDOMEN \- Prominent abdomen Liver \- Hepatomegaly Spleen \- Splenomegaly (variable) SKELETAL \- Joint contractures \- Narrowing of the joint spaces \- Periarticular osteopenia \- Bone pain \- Joint pain Limbs \- Elbow contractures Hands \- Finger contractures, severe \- Hand contractures, severe \- Clubbed fingers \- Long fingers \- Finger deformities \- Finger swelling Feet \- Toe contractures, severe \- Foot contractures, severe SKIN, NAILS, & HAIR Skin \- Erythematous nodular skin lesions \- Annular erythematous edematous plaques \- Lesions become purpuric \- Residual hyperpigmentation \- Lesions predominantly on face and limbs \- Panniculitis \- Dry, stiff skin \- Frostbitten hands Skin Histology \- Mononuclear cell infiltrates \- Atypical mononuclear cells with many mitoses MUSCLE, SOFT TISSUES \- Lipodystrophy, partial \- Lipodystrophy, generalized, panniculitis-induced (in some) \- Marked loss of subcutaneous fat in the limbs, face, and sometimes chest \- Muscle atrophy (variable) \- Muscle weakness NEUROLOGIC Central Nervous System \- Mental retardation, mild (2 families) \- Seizures (uncommon) \- Basal ganglia calcification METABOLIC FEATURES \- Fever, intermittent, recurrent (in some) HEMATOLOGY \- Microcytic anemia \- Thrombocytopenia IMMUNOLOGY \- Antinuclear autoantibodies (in some) \- Lymphadenopathy LABORATORY ABNORMALITIES \- Increased erythrocyte sedimentation rate \- Hypergammaglobulinemia \- Increased gamma-interferon \- Increased IgG \- Increased IgA \- Increased IL-6 \- Increased IL-8 \- Increased C-reactive protein \- Abnormal liver enzymes, intermittent \- Increased serum triglycerides MISCELLANEOUS \- Onset of autoinflammation in infancy or first few years of life \- Onset of lipodystrophy later in childhood \- Onset of joint contractures later in life \- Some features are variable MOLECULAR BASIS \- Caused by mutation in the proteasome subunit, beta-type, 8 gene (PSMB8, 177046.0001 ) ▲ 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	PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 1	c1850568	30,045	omim	https://www.omim.org/entry/256040	2019-09-22T16:24:27	{"mesh": ["C538334"], "omim": ["256040"], "orphanet": ["325004", "324999", "2615", "324977"], "synonyms": ["Alternative titles", "CHRONIC ATYPICAL NEUTROPHILIC DERMATOSIS WITH LIPODYSTROPHY AND ELEVATED TEMPERATURE SYNDROME", "NAKAJO-NISHIMURA SYNDROME", "JOINT CONTRACTURES, MUSCULAR ATROPHY, MICROCYTIC ANEMIA, AND PANNICULITIS-INDUCED LIPODYSTROPHY", "JMP SYNDROME", "AUTOINFLAMMATION, LIPODYSTROPHY, AND DERMATOSIS SYNDROME"]}
A number sign (#) is used with this entry because of evidence that thrombocytopenia-3 (THC3) is caused by homozygous mutation in the FYB gene (602731) on chromosome 5p13. Description Thrombocytopenia-3 is an autosomal recessive hematologic disorder characterized by onset of small-platelet thrombocytopenia in infancy. Patients may show variable bleeding tendency, manifest as petechiae, epistaxis, or heavy menstrual bleeding (summary by Levin et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900. Clinical Features Levin et al. (2013) reported 5 patients from a consanguineous Arab family with small-platelet thrombocytopenia apparent from infancy. The males had low-degree bleeding episodes, whereas 2 females developed severe bleeding during menstruation. Levin et al. (2015) reported follow-up of this family, noting that the patients had normal growth and development and absence of infections. Bone marrow aspirate from 1 patient showed reduced numbers of mature multilobulated megakaryocytes compared to controls, as well as increased megakaryocytes with nuclear hypersegmentation, suggesting abnormal maturation of megakaryocytes. Hamamy et al. (2014) reported a highly consanguineous kindred from northern Iraq in which 3 children had small-platelet thrombocytopenia. The patients presented in the first 5 years of life with evidence of bleeding, including generalized petechial rash and/or epistaxis. Laboratory studies showed normal hemoglobin concentration and leukocyte counts. There were no giant platelets. Bone marrow examination showed normocellular marrow with normal numbers of megakaryocytes and no abnormal cells. None of the patients had hepatosplenomegaly, skeletal or growth abnormalities, or immune defects. Inheritance The transmission pattern of THC3 in the family reported by Hamamy et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 members of a highly consanguineous kindred from northern Iraq with THC3, Hamamy et al. (2014) identified a homozygous frameshift mutation in the FYB gene (602731.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. In 5 patients from a large consanguineous Arab family with THC3, Levin et al. (2015) identified a homozygous truncating mutation in the FYB gene (602731.0002). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient platelets showed reduced pseudopodium formation and the presence of trapped platelets between fibrin fibers after thrombin addition compared to controls. Flow cytometric studies showed that patient fibroblasts had increased basal expression of P-selectin (173610) and PAC1, and reduced increments of activation markers after stimulation with ADP. Levin et al. (2015) noted that FYB is important for platelet activation, and that FYB-knockout mice have moderate thrombocytopenia. History Schaar (1963) described 4 brothers with idiopathic thrombocytopenic purpura that appeared in early infancy and was symptomatic. Three of the boys were well 14 years, 6 years, and 3 years following splenectomy. The other brother died of pneumococcal septicemia 3.5 years after splenectomy. The disorder was not associated with any other blood dyscrasia, platelet antibodies, or maternal antibodies. A platelet-stimulating factor was present. Bloom et al. (1966) described a form of constitutional aplastic anemia with 'amegakaryocytic thrombocytopenia present at birth or early infancy, followed later in childhood by pancytopenia.' They called it type II constitutional aplastic anemia. Maternal-fetal incompatibility of platelet antigens was a cause of neonatal thrombocytopenia in multiple sibs (Paganelli, 1969), simulating recessive inheritance. These patients were chronically thrombocytopenic but responded to the transfusion of normal plasma. Autosomal recessive inheritance has been reported by Roberts and Smith (1950) and by Wilson et al. (1963). INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Epistaxis GENITOURINARY Internal Genitalia (Female) \- Heavy menstrual flow SKIN, NAILS, & HAIR Skin \- Petechial rash HEMATOLOGY \- Thrombocytopenia \- Small platelets \- Mildly increased bleeding tendency \- Defect in megakaryocyte maturation MISCELLANEOUS \- Onset in first months or years of life \- Two unrelated consanguineous families have been reported (last curated April 2017) MOLECULAR BASIS \- Caused by mutation in the FYN-binding protein gene (FYB, 602731.0001 ) ▲ 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	THROMBOCYTOPENIA 3	c2678311	30,046	omim	https://www.omim.org/entry/273900	2019-09-22T16:21:45	{"doid": ["1588"], "mesh": ["C567487"], "omim": ["273900"], "orphanet": ["168629", "268322"], "synonyms": ["Alternative titles", "THROMBOCYTOPENIA, AUTOSOMAL RECESSIVE, 3"]}
Myeloid leukemia SpecialtyOncology, hematology Myeloid leukemia is a type of leukemia affecting myeloid tissue. Types include: * Acute myeloid leukemia * Chronic myelogenous leukemia * Acute megakaryoblastic leukemia * Blastic plasmacytoid dendritic cell neoplasm ## See also[edit] * Hematological malignancies * Myeloblast * transient myeloproliferative disease ## External links[edit] Classification D * ICD-10: C92 * ICD-9-CM: 205 * ICD-O: M9860/3 * MeSH: D007951 * SNOMED CT: 37810007 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia Index of articles associated with the same name This article includes a list of related items that share the same name (or similar names). If an internal link incorrectly led you here, you may wish to change the link to point directly to the intended article. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Myeloid leukemia	c0023470	30,047	wikipedia	https://en.wikipedia.org/wiki/Myeloid_leukemia	2021-01-18T18:44:13	{"gard": ["8226"], "mesh": ["D007951"], "umls": ["C0023470"], "wikidata": ["Q11688946"]}
A number sign (#) is used with this entry because of evidence that Huntington disease-like-2 (HDL2) is caused by a heterozygous expanded CAG/CTG repeat in the junctophilin-3 gene (JPH3; 605268) on chromosome 16q24. Normal alleles contain 6 to 28 repeats, whereas pathogenic alleles contain over 41 repeats (Todd and Paulson, 2010). Clinical Features Margolis et al. (2001) described a large kindred with an autosomal dominant disorder that is clinically similar to Huntington disease (143100) but arose from a CAG expansion in a different gene. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movements, psychiatric symptoms, weight loss, dementia, and relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal-to-ventral gradient and occasional intranuclear inclusions. This family was of African American ethnicity, and the parents of the first known affected individual were from a semirural region of the southeastern United States. The disorder in this family, designated family W, fell well within the spectrum of HD. Other than a lower frequency of eye movement findings and the absence of seizures, the disease was similar to juvenile-onset HD (van Dijk et al., 1986) and the 'Westphal' variant of HD observed in some adult cases. Unlike the HDL1 (603218), seizures did not occur in affected members of pedigree W. However, in both pedigrees, rigidity was more prominent than chorea. Walker et al. (2002) reported a family in which 3 individuals were affected with what the authors thought was an autosomal dominant form of chorea-acanthocytosis (200150), but which was later found by Walker et al. (2003) to be HDL2. The proband was a 56-year-old man who had initially been diagnosed with Huntington disease. At age 34 years, he developed a slowly progressive deterioration in memory and personality, with involuntary movements of the face and hands. By age 54 years, he was unable to stand, had no spontaneous speech, and showed continuous choreiform movements. Postmortem examination of the brain showed severe, diffuse cortical atrophy and severe atrophy of the caudate and putamen, as well as ubiquitinated intranuclear inclusions with immunoreactivity for expanded polyglutamine repeats throughout the brain. His son, who had fragile X syndrome (300624), developed gait abnormalities, chorea, and dystonia in his late twenties. Head CT scan showed generalized cerebral and caudate atrophy. Walker et al. (2002) suspected that the fragile X was unrelated to the neurologic disorder. The third patient, the nephew of the proband, developed personality changes, primitive reflexes, hyperreflexia, and mild parkinsonism beginning at age 28 years. All 3 patients had 30 to 35% acanthocytosis on peripheral blood smear. Pathogenesis Rudnicki et al. (2007) detected RNA foci within frontal lobe neurons of 4 patients with HDL2 using riboprobes specific for expanded CUG tracts and with riboprobes specific for JPH3 intron 1, exon 2A, or exon 2B. The RNA foci resembled those detected in DM1 (160900) in terms of size, restriction to nuclei, and colocalization with MBNL1 (606516). Approximately 30% of neurons contained foci, and most neurons contained more than 1 focus. Similar foci were also observed in the striatum. There was also a significant decrease in general MBNL1 expression compared to controls. No foci were detected in control brains or HD frontal cortex used as control. Overexpression of JPH3 transcripts containing an expanded CUG repeat expansion were toxic to HEK293 and HT22 cells, suggesting that the RNA transcripts play an important role in the pathogenesis of HDL2 via a toxic RNA gain-of-function effect. Molecular Genetics Margolis et al. (2001) found that in family W all tested affected individuals, and no tested unaffected individuals, had a CAG/CTG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other then-known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation was novel. Holmes et al. (2001) demonstrated that the expanded CAG/CTG repeat in the original pedigree was located in an alternatively spliced exon of the JPH3 gene (605268.0001). This exon has multiple splice acceptor sites. They found the same mutation in the JPH3 gene in other African American patients with a Huntington disease-like neurologic disorder. Among 74 patients with an HD-like phenotype but without CAG repeat expansions in the IT15 gene (HTT; 613004.0001), Stevanin et al. (2002) identified 1 patient with a pure uninterrupted 50 CAG/CTG repeat in the JPH3 gene. The patient was a 44-year-old Moroccan woman with subcortical dementia, mild choreic movements, and atrophy of the cerebral cortex. In the study by Stevanin et al. (2002), the HDL2 locus accounted for only 2% of typical HD cases not caused by expansion in the IT15 gene, suggesting further genetic heterogeneity. In the family reported by Walker et al. (2002) as having choreoacanthocytosis, Walker et al. (2003) identified trinucleotide repeat expansions of 51, 58, and 57 triplets in the junctophilin-3 gene, confirming Huntington disease-like-2. Walker et al. (2003) also reported a Mexican family with HDL2, characterized by dementia, depression, chorea, and parkinsonism, in which affected members had 46, 49, and 46 triplet repeats. One of the patients also had acanthocytosis. Another unrelated affected African American patient, who did not have acanthocytosis, had 44 triplet repeats. The findings indicated that some, but not all, patients with the HDL2 mutation may develop acanthocytosis, and Walker et al. (2003) suggested that there may be reduced penetrance of this feature or that the acanthocytosis may vary over the course of the disease. Population Genetics In 9 independent series of patients referred for HD testing in North America (538 patients) or Japan (44 patients), Margolis et al. (2004) found an HDL2 frequency of approximately 1% in North America and 0% in Japan. HDL2 was identified predominantly in patients of African ancestry. One affected Mexican pedigree originated from a region of Mexico colonized by Africans. Repeat expansions in the junctophilin-3 gene ranged from 44 to 57 triplets, and a younger age at onset was correlated with a longer repeat length. Rudnicki et al. (2007) stated that at least 25 HDL2 pedigrees had been identified; all with known ancestry are of definite or probable African origin. Santos et al. (2008) reported a 48-year-old Brazilian man of European ancestry who presented with a phenotype very suggestive of HD with onset of symptoms at age 44 years. His deceased father was reportedly similarly affected from age 50 years. Genetic analysis in the proband identified a 47 CTG repeat expansion in the JPH3 gene. Although the family did not refer to any African ancestry, the haplotype with the repeat expansion has only been identified in individuals of African ancestry (16.3%), suggesting that there was remote African ancestry in this family. Rodrigues et al. (2008) reported 4 unrelated Brazilian patients with HDL2 associated with heterozygous expanded repeat expansions of 47, 59, 46, and 48, respectively, in the JPH3 gene. Age at onset ranged from 22 to 60 years and was inversely correlated to the size of the repeat expansion. Three patients were black, consistent with African descent, and the fourth patient, who was white, was found to have a 'dark-skinned' grandmother, suggesting African ancestry. Rodrigues et al. (2008) noted that approximately 44.6% of the Brazilian population is of African descent. Nomenclature Margolis et al. (2001) stated that consistent with the recommendation of the Nomenclature Committee of HUGO, the disorder that maps to 20p is designated Huntington disease-like-1 (HDL1; 603218). They concluded that the family from Saudi Arabia that had been described as 'HD-like-3' is sufficiently distinct, based primarily on autosomal recessive inheritance and in part on presentation (onset age 3 to 4 years, prominent seizures, rapid course), to be classified separately. Since about 1% of all cases of clinically or pathologically defined HD do not carry the HD mutation, it was considered likely that the basis for other rare 'HD-like' disorders will be identified. INHERITANCE \- Autosomal dominant GROWTH Weight \- Weight loss NEUROLOGIC Central Nervous System \- Dystonia \- Chorea \- Rigidity \- Dysarthria \- Hyperreflexia \- Bradykinesia \- Dementia \- Action tremor \- Striatal atrophy Behavioral Psychiatric Manifestations \- Depression \- Anxiety \- Irritability \- Apathy \- Delusions \- Hallucinations MISCELLANEOUS \- Mean age of onset 35-40 years \- Normal alleles contain 6 to 28 repeats \- Pathogenic alleles contain greater than 41 repeats MOLECULAR BASIS \- Caused by a trinucleotide repeat expansion CAG(n) in the junctophilin-3 gene (JPH3, 605268.0001 ) ▲ 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	HUNTINGTON DISEASE-LIKE 2	c1847987	30,048	omim	https://www.omim.org/entry/606438	2019-09-22T16:10:28	{"doid": ["0090104"], "mesh": ["C564708"], "omim": ["606438"], "orphanet": ["98934"], "genereviews": ["NBK1529"]}
A tuberculoma is a clinical manifestation of tuberculosis which conglomerates tubercles into a firm lump, and so can mimic cancer tumors of many types in medical imaging studies.[1][2] Since these are evolutions of primary complex, the tuberculomas may contain within caseum or calcifications. ## Contents * 1 Cause * 2 Diagnosis * 2.1 Differential diagnosis * 3 Treatment * 4 References ## Cause[edit] With the passage of time Mycobacterium tuberculosis can transform into crystals of calcium. These can affect any organ such as the brain,[3][4] intestine,[5][6][7] ovaries,[8][9] breast,[10][11][12] lungs,[13][14] esophagus,[15] liver,[citation needed] pancreas,[16] bones,[17][18] and many others. ## Diagnosis[edit] ### Differential diagnosis[edit] As the histologic and clinical indications, as well as tumor markers such as the CA-125, are similar, it is often difficult to differentiate tuberculoma from cancer. For these reasons, tuberculosis should always be considered in the differential diagnosis of cancer. ## Treatment[edit] Tuberculoma is commonly treated through the HRZE drug combination (Isoniazid, Rifampin, Pyrazinamide, Ethambutol) followed by maintenance therapy.[19] ## References[edit] 1. ^ Pitlik SD, Fainstein V, Bodey GP (May 1984). "Tuberculosis mimicking cancer--a reminder". The American Journal of Medicine. 76 (5): 822–5. doi:10.1016/0002-9343(84)90993-8. PMID 6720729. 2. ^ Vento S, Lanzafame M (June 2011). "Tuberculosis and cancer: a complex and dangerous liaison". The Lancet. Oncology. 12 (6): 520–2. doi:10.1016/S1470-2045(11)70105-X. PMID 21624773. 3. ^ Dennison P, Rajakaruna G (October 2006). "Cerebral tuberculoma". Thorax. 61 (10): 922. doi:10.1136/thx.2005.054932. PMC 2104774. PMID 17008487. 4. ^ Chatterjee S (October 2011). "Brain tuberculomas, tubercular meningitis, and post-tubercular hydrocephalus in children". Journal of Pediatric Neurosciences. 6 (Suppl 1): S96–S100. doi:10.4103/1817-1745.85725. PMC 3208909. PMID 22069437. 5. ^ Herrick FC (April 1925). "Tuberculoma of the Caecum: Hyperplastic Tuberculosis". Annals of Surgery. 81 (4): 801–20. doi:10.1097/00000658-192504000-00009. PMC 1399989. PMID 17865239. 6. ^ Chakravartty S, Chattopadhyay G, Ray D, Choudhury CR, Mandal S (2010). "Concomitant tuberculosis and carcinoma colon: coincidence or causal nexus?". Saudi Journal of Gastroenterology. 16 (4): 292–4. doi:10.4103/1319-3767.70619. PMC 2995101. PMID 20871197. 7. ^ Kushwaha JK, Sonkar AA, Saraf A, Singh D, Gupta R (September 2011). "Jejunal adenocarcinoma: an elusive diagnosis". Indian Journal of Surgical Oncology. 2 (3): 197–201. doi:10.1007/s13193-011-0101-7. PMC 3272177. PMID 22942611. 8. ^ Elmore RG, Li AJ (December 2007). "Peritoneal tuberculosis mimicking advanced-stage epithelial ovarian cancer". Obstetrics and Gynecology. 110 (6): 1417–9. doi:10.1097/01.AOG.0000295653.32975.4a. PMID 18055741. 9. ^ Rabesalama S, Mandeville K, Raherison R, Rakoto-Ratsimba H (2011). "Isolated ovarian tuberculosis mimicking ovarian carcinoma: case report and literature review". African Journal of Infectious Diseases. 5 (1): 7–10. doi:10.4314/ajid.v5i1.66508. PMC 3497843. PMID 23878702. 10. ^ Baharoon S (July 2008). "Tuberculosis of the breast". Annals of Thoracic Medicine. 3 (3): 110–4. doi:10.4103/1817-1737.41918. PMC 2700437. PMID 19561892. 11. ^ Sen M, Gorpelioglu C, Bozer M (2009). "Isolated primary breast tuberculosis: report of three cases and review of the literature". Clinics. 64 (6): 607–10. doi:10.1590/S1807-59322009000600019. PMC 2705158. PMID 19578668. 12. ^ Akçay MN, Sağlam L, Polat P, Erdoğan F, Albayrak Y, Povoski SP (June 2007). "Mammary tuberculosis -- importance of recognition and differentiation from that of a breast malignancy: report of three cases and review of the literature". World Journal of Surgical Oncology. 5: 67. doi:10.1186/1477-7819-5-67. PMC 1910599. PMID 17577397. 13. ^ Liang HY, Li XL, Yu XS, Guan P, Yin ZH, He QC, Zhou BS, et al. (December 2009). "Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review". International Journal of Cancer. 125 (12): 2936–44. doi:10.1002/ijc.24636. PMID 19521963. 14. ^ Khan AN, Al-Jahdali HH, Allen CM, Irion KL, Al Ghanem S, Koteyar SS (April 2010). "The calcified lung nodule: What does it mean?". Annals of Thoracic Medicine. 5 (2): 67–79. doi:10.4103/1817-1737.62469. PMC 2883201. PMID 20582171. 15. ^ Patnayak R, Reddy MK, Parthasarathy S, Yootla M, Reddy V, Jena A (April 2008). "Unusual presentation of esophageal tuberculosis mimicking malignancy". Saudi Journal of Gastroenterology. 14 (2): 103–4. doi:10.4103/1319-3767.39632. PMC 2702907. PMID 19568514. 16. ^ Saluja SS, Ray S, Pal S, Kukeraja M, Srivastava DN, Sahni P, Chattopadhyay TK (June 2007). "Hepatobiliary and pancreatic tuberculosis: a two decade experience". BMC Surgery. 7 (1): 10. doi:10.1186/1471-2482-7-10. PMC 1925057. PMID 17588265. 17. ^ Herzog A (September 2009). "Dangerous errors in the diagnosis and treatment of bony tuberculosis". Deutsches Ärzteblatt International. 106 (36): 573–7. doi:10.3238/arztebl.2009.0573. PMC 2770211. PMID 19890413. 18. ^ Dhillon MS, Aggarwal S, Prabhakar S, Bachhal V (March 2012). "Tuberculosis of the foot: An osteolytic variety". Indian Journal of Orthopaedics. 46 (2): 206–11. doi:10.4103/0019-5413.93683. PMC 3308663. PMID 22448060. 19. ^ Monteiro R, Carneiro JC, Costa C, Duarte R (2013). "Cerebral tuberculomas - A clinical challenge". Respiratory Medicine Case Reports. 9: 34–7. doi:10.1016/j.rmcr.2013.04.003. PMC 3949551. PMID 26029627. This infectious disease 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	Tuberculoma	c0041295	30,049	wikipedia	https://en.wikipedia.org/wiki/Tuberculoma	2021-01-18T18:34:21	{"mesh": ["D014375"], "umls": ["C0041295"], "wikidata": ["Q4464809"]}
Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles. ## Epidemiology The prevalence is estimated to be 1/5,000 and the incidence to be 1/250,000 to 1/33,000 in Europe. MG affects both males and females: mainly females before the age of 40 years and males and females equally after the age of 50 years. ## Clinical description Myasthenia gravis can develop at any age but there is a bimodal peak in the age of onset in the adult-onset form, with primarily female patients before 40 years of age, and primarily males after 50 years of age (adult-onset myasthenia gravis; see this term). Patients have fluctuating weakness, worsening with repetitive activities, heat and stress while improving with rest and with involvement of skeletal muscle groups of ocular, bulbar, extremities and neck. Ocular manifestations include fluctuating diplopia and ptosis. Bulbar involvement may manifest with fatigable chewing, dysphagia and dysarthria. Some patients develop generalized muscle weakness, which may become serious with respiratory muscle weakness. In the juvenile form, onset is before 18 years of age (juvenile myasthenia gravis; see this term) and patients also present with ocular and possibly generalized muscle weakness. A transient neonatal form causing hypotonia and feeding difficulties occurs in some newborns born to mothers with MG (transient neonatal myasthenia gravis; see this term). Congenital genetic forms of MG with a different pathogenesis also occur (congenital myasthenic syndrome, see this term). ## Etiology The exact pathogenesis is not known but MG is related to circulating antibodies to various muscle receptors, including acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). Another target, the low density lipoprotein receptor-related protein 4 (LRP4), has been also described. The thymus is thought to trigger antibody production in the form with anti-AChR antibodies. These antibodies have been found to play a pathogenic role in all the forms of the disease. MG can also be drug induced (by D-penicillamine, interferon alpha, and bone marrow transplantation). An initial infection (EBV) may be responsible for some cases of MG. The role of infections has been strongly suggested by evidence of the involvement of interferon type I in the disease, but direct evidence is lacking. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Myasthenia gravis	c0026896	30,050	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=589	2021-01-23T18:49:23	{"gard": ["7122"], "mesh": ["D009157"], "omim": ["159400", "254200", "607085"], "umls": ["C0026896"], "icd-10": ["G70.0"], "synonyms": ["Acquired myasthenia", "Autoimmune myasthenia gravis"]}
This article needs attention from an expert in Genetics. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Genetics may be able to help recruit an expert. (August 2008) Hydrolethalus syndrome Other namesSalonen-Herva-Norio syndrome Hydrolethalus syndrome is inherited in an autosomal recessive manner SpecialtyMedical genetics Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.[1] HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper cilial development within the human body. Cilia are microscopic projections that allow sensory input and signalling output within cells, as well as cell motility.[2] Dysfunction results in a range of abnormalities that are often the result of improper cell signalling.[3] A variant form, HLS2, with additional mutations to the KIF7 gene, is less common.[4] KIF7 also ensures correct cilia formation and function, specifically cilia stability and length.[5] Hydrolethalus syndrome (HLS) was first mistakenly identified in Finland, during a study on Meckel syndrome.[6] Like HLS, Meckel syndrome presents with severe physiological abnormalities, namely disruptions to the central nervous system and the presence of extra fingers or toes (polydactyly).[6] HLS can be distinguished from Meckel syndrome by analysing kidney function, which is dysfunctional in Meckel syndrome as a result of cyst formation.[7] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Genetic * 2.2 Environmental * 3 Pathophysiology * 3.1 Variations and related pathologies * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] HLS presents itself as various, lethal developmental abnormalities, which often result in either premature stillbirth or death shortly after birth.[6] Rare cases of children born with HLS surviving for several months have been noted.[7] A characteristic abnormality of HLS is an absence of brain tissue and midline structures, with the presence of excess brain fluid (hydrocephalus) as a result of abnormal development of the central nervous system.[6] Other common defects include incomplete lung development, heart defects, a cleft lip or palate, polydactyly, and an abnormally small jaw.[6] Stillbirth and an excess of amniotic fluid (polyhydramnios) are common during pregnancy with a HLS-affected foetus, with cases of up to 8 litres cited compared to the normal 1 litre.[7] Less common symptoms such as abnormally small eyes and a broad nose are also possible.[citation needed] ## Cause[edit] ### Genetic[edit] HLS is caused by a genetic missense mutation of the HYLS1 gene, encoding for Hydrolethalus syndrome protein 1, on chromosome 11;[7] a single base change to the amino acid sequence for HYLS1 in exon 6 involves the replacement of aspartic acid 211 with glycine (D211G) in the polypeptide chain.[8] Exon 6 is the only protein coding exon in HYLS1; proper functioning of exons 1-5 ensures regulation and expression of the entire protein.[7] HLS is an autosomal recessive syndrome;[9] development is only possible if both parents carry the defective gene, and in that instance, the risk of the foetus developing the syndrome is 25%. HLS is a member of the Finnish disease heritage,[7] with incidences more common in Finland than the rest of the world; roughly 1 in 20,000 developing foetuses are affected in Finland.[6] Rare cases in other regions have also been documented, often with less severe phenotypes as a result of allele variability across countries, allowing survival of affected offspring for up to several months.[7] Individuals of Finnish descent are advised to undergo genetic testing before attempting to conceive.[citation needed] Prior to the discovery of HLS, the HYLS1 gene was unknown, and similar genes within humans have not been identified.[7] Orthologs, genes in other species with common ancestral heritage, have been examined to explain the pathophysiology of HLS; a similar gene within the roundworm, Caenorhabditis elegans, is responsible for the formation of cilia.[10] Current hypotheses place a dysfunction of cilia as the main cause of HLS defects arising from the HYLS1 mutation in humans.[7][9] Differences between wild type and mutant HYLS1 have been clearly observed; the wild type form is localised to the cytoplasm, while the mutant form is localised to the nucleus and forms small clusters, suggesting that the mutant gene disrupts cellular localisation.[9] The protein encoded by the HYLS1 mutant form is unable to carry out essential targeting of centrioles to the plasma membrane, disrupting ciliary function, which results in ciliopathy.[10] As cilia are located in almost all cells throughout the body, cilial dysfunction causes developmental defects in a range of organs and thus the phenotype of HLS can vary greatly, though brain malformation and polydactyly are most commonly observed. ### Environmental[edit] Currently, no environmental factors are known to increase the likelihood of HLS development or progression; HLS is caused only by genetic abnormalities.[5] ## Pathophysiology[edit] The pathophysiology of HLS is abnormal cilia development arising from the inability of the mutated HYLS1 gene to correctly target centrioles to the plasma membrane.[10] Specifically, transition fibres within the transition zone, at the base of the axoneme and adjoining to the plasma membrane, lack proper development.[11] As these structures form the cilial gate, improper development results in a loss of selectivity for protein entry into the ciliary compartment.[5] ### Variations and related pathologies[edit] Mutations in KIF7 have also been noted in patients that present a similar phenotype to HLS and the characteristic HYLS1 A to G transformation; homozygous deletion of the KIF7 gene causes a variant form of HLS, HLS2.[4] KIF7 encodes a structural factor vital to cilial transport, and is also implicated in other developmental disorders, such as Joubert syndrome (JS).[2] Additionally, mutations in HYLS1 are no longer explicitly connected to HLS in humans.[2] Homozygous mutations removing the stop codon in exon 4 of HYLS1 result in a different genomic sequence disruption to the missense mutation of HLS, and phenotypically present as JS.[3] The ‘molar tooth sign’ of the brain, an anomaly in which cerebellar volume is reduced but cerebellar shape is retained, resembles the molar tooth and is used to identify JS.[2] JS presents with mutations in more than 30 genes, whilst the HYLS1 mutation is the sole cause of HLS, but is also present in the HLS2 variant form with the mutated KIF7 gene.[4] ## Diagnosis[edit] HLS can be readily diagnosed during pregnancy through the use of ultrasound, which will often reveal hydrocephaly and an abnormal structure of the brain.[12] Precise examination via ultrasound or at birth is necessary to rule out Meckel syndrome, Trisomy 13, or Smith–Lemli–Opitz syndrome, which present with similar physiological defects.[7] HLS can be detected at the end of the first trimester, approximately 13 weeks gestation.[8] ## Treatment[edit] No cure or treatment option for individuals with HLS currently exist.[12] Due to the severity of the foetal defects and the poor prognosis for those with HLS, the pregnancy is often terminated.[7] Certain prevention can only be achieved by avoiding conception if genetic testing indicates both prospective parents as carriers of the defective HYLS1 gene.[9] ## See also[edit] •HYLS1 ## References[edit] 1. ^ E-Notes: Hydrolethalus Syndrome 2. ^ a b c d Oka M, Shimojima K, Yamamoto T, Hanaoka Y, Sato S, Yasuhara T, Yoshinaga H, Kobayashi K (June 2016). "A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome". Clinical Genetics. 89 (6): 739–43. doi:10.1111/cge.12752. PMID 26830932. 3. ^ a b Waters A, Beales P (July 2011). "Ciliopathies: an expanding disease spectrum". Pediatric Nephrology. 26 (7): 1039–56. doi:10.1007/s00467-010-1731-7. PMC 3098370. PMID 21210154. 4. ^ a b c Putoux A, Thomas S, Coene K, Davis E, Alanay Y, Ogur G, Uz E, Buzas D, Gomes C, Patrier S, Bennett C, Elkhartoufi N, Frison M, Rigonnot L, Joyé N, Pruvost S, Utine G, Boduroglu K, Nitschke P, Fertitta L, Thauvin-Robinet C, Munnich A, Cormier-Daire V, Hennekam R, Colin E, Akarsu N, Bole-Feysot C, Cagnard N, Schmitt A, Goudin N, Lyonnet S, Encha-Razavi F, Siffroi J, Winey M, Katsanis N, Gonzales M, Vekemans M, Beales P, Attié-Bitach T (June 2011). "KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes". Nature Genetics. 43 (6): 601–6. doi:10.1038/ng.826. PMC 3674836. PMID 21552264. 5. ^ a b c Takao D, Verhey K (January 2016). "Gated entry into the ciliary compartment". Cellular and Molecular Life Sciences. 73 (1): 119–27. doi:10.1007/s00018-015-2058-0. PMC 4959937. PMID 26472341. 6. ^ a b c d e f Salonen R, Herva R (December 1990). "Hydrolethalus syndrome". Journal of Medical Genetics. 27 (12): 756–59. doi:10.1136/jmg.27.12.756. PMC 1017280. PMID 2074561. 7. ^ a b c d e f g h i j k Honkala H (March 2009). "The molecular basis of hydrolethalus syndrome". ResearchGate: 756–59. 8. ^ a b Honkala H, Lahtela J, Fox H, Gentile M, Pakkasjärvi N, Salonen R, Wartiovaara K, Jauhiainen M, Kestilä M (April 2009). "Unraveling the disease pathogenesis behind lethal Hydrolethalus syndrome revealed multiple changes in molecular and cellular level". PathoGenetics. 2 (2): 2. doi:10.1186/1755-8417-2-2. PMC 2686686. PMID 19400947. 9. ^ a b c d Mee L, Honkala H, Kopra O, Vesa J, Finnilä S, Visapää I, Sang T, Jackson G, Salonen R, Kestilä M, Peltonen L (April 2005). "Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1". Human Molecular Genetics. 14 (11): 1475–88. doi:10.1093/hmg/ddi157. PMID 15843405. 10. ^ a b c Dammermann A, Pemble H, Mitchell B, McLeod I, Yate J, Kintner C, Desai A, Oegema K (September 2009). "The Hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation". Genes & Development. 23 (17): 2046–59. doi:10.1101/gad.1810409. PMC 2751977. PMID 19656802. 11. ^ Wei Q, Zhang Y, Schouteden, C, Zhang, Y, Zhang, Q, Dong, J, Wonesch, V, Ling, K, Dammermann, A, Hu, J (August 2016). "The hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate". Nature Communications. 7 (12437): 12437. Bibcode:2016NatCo...712437W. doi:10.1038/ncomms12437. PMC 4992140. PMID 27534274. 12. ^ a b "Orphanet: Hydrolethalus". 2017-09-10. Retrieved 2017-09-10. ## External links[edit] Classification D * ICD-10: Q87.8 * OMIM: 236680 * MeSH: C536079 * DiseasesDB: 34380 * SNOMED CT: 721232000 External resources * Orphanet: 2189 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hydrolethalus syndrome	c2931104	30,051	wikipedia	https://en.wikipedia.org/wiki/Hydrolethalus_syndrome	2021-01-18T18:40:15	{"gard": ["6683"], "mesh": ["C536079"], "umls": ["C2931104"], "orphanet": ["2189"], "wikidata": ["Q5955105"]}
Rather extensive literature supporting dominant inheritance was reviewed by Gates (1946). Klinkerfuss (1924) found polymastia in 5 females in 4 generations. The extra breast consisted of a mass in one or both axillae which enlarged in pregnancy and lactation. In some, a nipple was associated with the adventitious breast tissue. It may have communicated with the main breast tissue because it swelled before nursing and shrunk with nursing. Pierre Marie (1893) also observed supernumerary breasts in 4 generations and noted an association with twinning. Weinberg and Motulsky (1976) reported a kindred in which 6 adult females in 2 generations showed bilateral accessory axillary breast without nipples or areolae. They concluded that the anomaly is probably caused by an autosomal dominant gene of variable expressivity which prevents normal regression of the embryonal mammary bridge. Without areolae or nipples, the trait is usually not detectable in prepubertal females and in males of all ages. Leung (1988) reported supernumerary nipples in a Chinese man and his identical twin daughters. The supernumerary nipples were situated below the normal nipples, which is usually the case in Caucasians. In Japanese women, according to Iwai (1907), 82% of instances of supernumerary nipples show a location above the normal breasts. An association with renal anomalies has been suggested (Meggyessy and Mehes, 1987). Rintala and Norio (1982) reported dysplastic divided nipples (intraareolar polythelia) bilaterally in a mother, her 2 daughters, and 1 son. By selective breeding in sheep, Alexander Graham Bell (1898) succeeded in producing 2 to 4 accessory nipples in 90% of the offspring. In the guinea pig this trait behaves as an autosomal dominant (Goertzen and Ibsen, 1951). Toumbis-Ioannou and Cohen (1994) described polythelia in 3 sibs, 2 sisters and a brother. They tabulated reports of same in the English language literature starting with that by Iwai (1907). Multigeneration involvement was the rule. Urbani and Betti (1995) claimed that there is an association between familial polythelia and kidney and urinary tract malformations. In a subsequent report, Urbani and Betti (1997) reported an association between supernumerary nipples and Becker nevus (see 604919). They suggested this observation may be explained by the concept of paradominant inheritance proposed by Happle (1992) for Becker nevus. The idea of paradominant inheritance as described by Happle (1992) is that heterozygous gene carriers are usually phenotypically normal, and consequently the altered gene can be transmitted through multiple generations without phenotypic manifestation. Only when a somatic mutation occurs, resulting in a mosaic patch of cells homozygous for the mutation (or hemizygous), does a trait become evident. Schmidt (1998) studied the prevalence, size, and predilections for sex and side of supernumerary nipples in a prospective clinical study. Of 502 individuals, 28 (5.6%) exhibited a supernumerary nipple, which was classified as small (areola only, diameter less than 30% of normal) in 21 persons and middle-sized (30 to 50% of normal) in 7 persons. The male/female ratio was 20 to 8 and the left/right side ratio was 15 to 7 in males and 5 to 4 in females. In 40% of individuals, one of the parents confirmed the presence of a supernumerary nipple. None of the 28 had a history of urinary tract infection or suspected urinary tract malformation. Hundleby and Beighton (2007) described a South African woman with bilateral duplication of the nipples and areolae in an apparently horizontal plane without mammary tissue reduplication. The authors stated that this configuration of breast tissue had not previously been described. The family history was negative for any abnormalities of the breasts. INHERITANCE \- Autosomal dominant CHEST Breasts \- Accessory breast \- Supernumerary nipples (polythelia) ▲ 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	NIPPLES, SUPERNUMERARY	c0266011	30,052	omim	https://www.omim.org/entry/163700	2019-09-22T16:37:22	{"mesh": ["C562557"], "omim": ["163700"], "icd-10": ["Q83.3"], "orphanet": ["2456"], "synonyms": ["Alternative titles", "ACCESSORY NIPPLES", "POLYMASTIA", "POLYTHELIA, FAMILIAL"]}
A rare form of pseudohyperaldosteronism characterized by very early-onset and severe hypertension, associated with low renin levels and hypoaldosteronism. ## Epidemiology Prevalence is difficult to estimate and likely varies between populations depending on the level of consanguinity. Less than 100 cases have been reported in the literature so far. ## Clinical description AME is usually diagnosed within the first years of life and is characterized by polyuria and polydipsia, failure to thrive, severe hypertension with low renin and aldosterone levels, profound hypokalemia with metabolic alkalosis, and most often nephrocalcinosis. Stroke has been observed before the age of 10 years in untreated children. ## Etiology AME is caused by homozygous or compound heterozygous loss-of-function mutations or deletions in the HSD11B2 gene (16q22). In all cases, these mutations lead to abolition or a marked decrease in the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), an enzyme involved in the conversion of cortisol to cortisone. ## Diagnostic methods Diagnosis should be suspected on the basis of the clinical and biochemical characteristics. Detection of a marked increase (10 to 100-fold) in the ratio of cortisol/cortisone (F/E) or of the tetrahydroxylated metabolites (THF+alloTHF/THE) in plasma and urine is a strong indication for diagnosis. However, a milder form of AME (AME2, also caused by mutations in the HSD11B2 gene) has been described with less marked hypertension and only mild abnormalities of cortisol metabolism. The diagnosis can be confirmed by genetic testing. ## Differential diagnosis Differential diagnoses include pseudohyperaldosteronism (particularly Liddle syndrome; see this term), as well as other forms of early-onset childhood hypertension (particularly renal hypertension). Natural licorice consumption can result in a clinical picture that mimics AME, but this phenomenon is only rarely observed in children as it requires either a sustained and chronic, or a high and acute, exposure to cause adverse effects. ## Antenatal diagnosis For families in which the disease-causing mutation has already been identified, prenatal diagnosis may be considered in case of a life-threatening case in a previous child. ## Genetic counseling Transmission is autosomal recessive. ## Management and treatment Early diagnosis and treatment is important to prevent end-organ damage (central nervous system, kidney, heart and retina). Two main strategies can be used to treat AME. The first is the blockade of the mineralocorticoid receptor by spironolactone (2-10 mg/kg/day), combined with thiazides to help to normalize blood pressure and reduce hypercalciuria and nephrocalcinosis. The second and complementary strategy, is the administration of exogenous corticoids to block ACTH and suppress the endogenous secretion of cortisol. This strategy has proven efficacy on blood pressure, renin and aldosterone levels but has little effect on urinary cortisol, cortisone and corticosterone concentrations. As the hypertension is severe, nonspecific antihypertensive agents (e.g. calcium antagonists) are also often required. ## Prognosis In the absence of treatment, the prognosis for AME is severe with malignant hypertension, stroke, cardiac and renal insufficiency. However, the prognosis for patients with appropriate treatment appears to be good. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Apparent mineralocorticoid excess	c0342488	30,053	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=320	2021-01-23T19:10:35	{"gard": ["433"], "mesh": ["D043204", "C537422"], "omim": ["218030"], "umls": ["C0342488", "C2936861", "C3887949"], "icd-10": ["E26.1"], "synonyms": ["11-beta-hydroxysteroid dehydrogenase deficiency type 2", "Ulick syndrome"]}
For a general description and a discussion of genetic heterogeneity of sarcoidosis, see 181000. Mapping Hofmann et al. (2008) performed a genomewide association study with greater than 440,000 single-nucleotide polymorphisms (SNPs) for sarcoidosis comprising 499 German individuals with sarcoidosis and 490 controls, and detected a series of genetic associations. The strongest association signal mapped to the ANXA11 gene (602572) on chromosome 10q22.3. Validation in an independent sample (1,649 cases, 1,832 controls) confirmed the association (for rs2789679, P = 3.0 x 10(-13)). Extensive fine mapping located the association signal to a region between exon 5 and exon 14 of ANXA11. A common nonsynonymous SNP (rs1049550, C-to-T, R230C) was found to be strongly associated with sarcoidosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SARCOIDOSIS, SUSCEPTIBILITY TO, 3	c0036202	30,054	omim	https://www.omim.org/entry/612388	2019-09-22T16:01:34	{"mesh": ["D012507"], "omim": ["612388"], "orphanet": ["797"]}
GM2 gangliosidosis, AB variant is an extremely rare, severe genetic disorder characterized by progressive neurological decline due to ganglioside activator deficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GM2 gangliosidosis, AB variant	c0268275	30,055	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309246	2021-01-23T18:11:06	{"mesh": ["D049290"], "omim": ["272750"], "umls": ["C0268275"], "icd-10": ["E75.0"], "synonyms": ["Hexosaminidase activator deficiency"]}
Refractory anemia with excess blasts (RAEB) is a frequent severe subtype of myelodysplastic syndrome (MDS; see this term) characterized by cytopenias with unilineage or multilineage dysplasia and 5% to 19% blasts in bone marrow or blood. ## Epidemiology Exact prevalence is unknown but RAEB accounts for about 40% of patients with MDS which has a prevalence estimated to be 1/25,000 to 1/33,000. The disease tends to occur in older adults with a male predominance. ## Clinical description Two types of RAEB are recognized: type 1 and type 2 (RAEB-1 and RAEB-2; see these terms) which are differentiated based on the percentage of blasts in bone marrow or blood. Patients usually present with symptoms related to one or more cytopenias. Survival is lower in patients with RAEB-2 and there is a higher rate of transformation into acute myeloid leukemia in these patients. Most RAEB patients die from neutropenia-, thrombocytopenia- and anemia-related complications. ## Etiology The etiology is not known but is thought to involve inherited susceptibility or hematopoietic stem cell damage. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Refractory anemia with excess blasts	c0002894	30,056	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86839	2021-01-23T18:00:03	{"mesh": ["D000754"], "umls": ["C0002894"], "icd-10": ["D46.2"], "synonyms": ["RAEB"]}
A rare autosomal recessive cerebellar ataxia characterized by early onset of slowly progressive cerebellar atrophy, clinically manifesting with extremity and truncal ataxia, global developmental delay, intellectual impairment, nystagmus, dysarthria, intention tremor, and pyramidal signs, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 recessive cerebellar ataxia due to CWF19L1 deficiency	c4015301	30,057	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=453521	2021-01-23T17:28:12	{"omim": ["616127"], "icd-10": ["G11.1"], "synonyms": ["SCAR17", "Spinocerebellar ataxia autosomal recessive type 17"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Penile torsion is a fairly common congenital condition with male infants. It occurs up to about 1 in 80 newborn males. With this condition, the penis appears rotated on its axis, almost always to the left (counterclockwise).[1] ## See also[edit] * Chordee ## References[edit] 1. ^ Eroglu, Egemen; Gundogdu, Gokhan (2015-01-01). "Isolated penile torsion in newborns". Canadian Urological Association Journal. 9 (11–12): E805–E807. doi:10.5489/cuaj.2833. ISSN 1911-6470. PMC 4639432. PMID 26600889. * Bar-Yosef Y, Binyamini J, Matzkin H, Ben-Chaim J. Degloving and realignment—simple repair of isolated penile torsion. Urology 2007 Feb;69(2):369-71. * Bauer R, Kogan BA. Modern technique for penile torsion repair. J Urol. 2009 Jul;182(1):286-90 * Snow BW. Penile torsion correction by diagonal corporal plication sutures. Int Braz J Urol. 2009 Jan-Feb;35(1):56-9 * Abdelhamid A, Zeid A, Soliman H. Penile torsion: An overlooked anomaly with distal hypospadias. Annals of Pediatric Surgery 2010 Apr; 6(2)93-97. * Wilcox D, Godbole P, Cooper C.Pediatric Urology Book ## External links[edit] * Penile torsion image [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Penile torsion	c4076085	30,058	wikipedia	https://en.wikipedia.org/wiki/Penile_torsion	2021-01-18T19:08:10	{"umls": ["C4076085"], "wikidata": ["Q30314170"]}
## Description Autoimmune thrombocytopenic purpura is characterized by a low platelet count, normal bone marrow, and the absence of other causes of thrombocytopenia. It is principally a disorder of increased platelet destruction mediated by autoantibodies to platelet-membrane antigens (George et al., 1994). Clinical Features In children, AITP is usually acute and self-limited, whereas in adults, it is most often chronic. The presenting features are bruising, petechiae, and/or mucosal bleeding (epistaxis, hematuria, and rarely intracerebral hemorrhage) (George et al., 1994). Cines and Blanchette (2002) and Imbach et al. (2002) provided comprehensive reviews. Inheritance Karpatkin et al. (1981) described autoimmune thrombocytopenic purpura in a woman and 3 of her 4 children (a son and 2 daughters). Bound platelet antibody was demonstrated. They found reports of 4 families of probable similar disorder. Laster et al. (1982) described chronic immune thrombocytopenic purpura in monozygotic twins. Imbach et al. (2002) cited Dohrn in Germany as describing purpura hemorrhagica in a neonate and his mother. Pathogenesis Harrington et al. (1951) observed a child with purpura born to a mother with chronic idiopathic thrombocytopenic purpura. The child's purpura resolved spontaneously within 3 weeks while the mother remained thrombocytopenic. Harrington argued that transfer of a humoral antiplatelet factor from the mother to her baby occurred. He then administered plasma from patients with chronic AITP to himself and to 9 volunteers with a normal platelet count. Eight of the recipients immediately developed transient thrombocytopenia and some of them purpura as well. One of the volunteers, in spite of an earlier splenectomy, also responded with thrombocytopenia, indicating a secondary role of the spleen. Imbach et al. (2002) stated that Harrington's experiment clearly suggested an antiplatelet factor in the plasma as the cause of AITP. They also noted that evidence for the role of autoantibodies in chronic AITP was first reported by van Leeuwen et al. (1982). Clinical Management Gasbarrini et al. (1998) reported that successful eradication of Helicobacter pylori infection in ITP patients, as assessed by the urea breath test, resulted in a significant increase in platelet counts and, in 6 of the 8 patients, in the disappearance of anti-platelet antibodies. Fujimura et al. (2005) analyzed more than 200 ITP patients and observed a benefit from successful eradication of H. pylori in most patients. Complete remission was 23% in the successfully treated group, 12 months after eradication. Asahi et al. (2008) observed increased platelet numbers following anti-H. pylori treatment only in H. pylori-positive ITP patients. Before treatment, monocytes from H. pylori-positive patients exhibited enhanced phagocytic capacity and low levels of the inhibitory FCGR2B (604590) receptor. Treatment suppressed the activated monocyte phenotype and improved autoimmunity parameters and modulation of the balance of Fc-gamma receptors. Asahi et al. (2008) suggested that platelet recovery in successfully treated ITP patients is mediated through a change in Fc-gamma receptor balance toward the inhibitory FCGR2B type. Molecular Genetics Breunis et al. (2008) found that an ORF allele of the FCGR2C gene (612169) was significantly overrepresented in patients with autoimmune thrombocytopenic purpura, with 34% of AITP patients having at least 1 ORF allele. Inheritance \- Autosomal dominant form Lab \- Platelet antibody Heme \- Bleeding diathesis \- Thrombocytopenia ▲ 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	THROMBOCYTOPENIC PURPURA, AUTOIMMUNE	c0398650	30,059	omim	https://www.omim.org/entry/188030	2019-09-22T16:32:41	{"doid": ["8924"], "mesh": ["D016553"], "omim": ["188030"], "icd-9": ["287.31"], "icd-10": ["D69.3"], "orphanet": ["3002"], "synonyms": ["Alternative titles", "IMMUNE THROMBOCYTOPENIC PURPURA", "IDIOPATHIC THROMBOCYTOPENIC PURPURA"]}
A rare congenital hemangioma characterized by a superficial, red to violaceous lesion with overlying telangiectasia and a surrounding pale halo, which initially behaves like a rapidly involuting congenital hemangioma, beginning to involute shortly after birth. Involution is then aborted, and a residual tumor virtually indistinguishable from non-involuting congenital hemangioma remains. This lesion grows proportionally with the child and does not regress. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Partially involuting congenital hemangioma	None	30,060	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=458785	2021-01-23T17:34:56	{"icd-10": ["D18.0"]}
A malignant peripheral nerve sheath tumor (MPNST) is a tumor that develops in the protective lining that covers nerves. The first symptom of MPNST is often a lump or mass that increases in size, sometimes causing pain or a tingling sensation. MPNST is considered an aggressive tumor because there is up to a 65% chance of the tumor regrowing after surgery (a recurrence), and approximately 40% chance of spreading to distant parts of the body (a metastasis), most commonly to the lung. Treatment of MPNST begins with surgery to remove as much of the tumor as possible. Radiation therapy may be used to decrease the chance of a recurrence. Chemotherapy might be used if the whole tumor cannot be removed during surgery, or to treat a metastasis. MPNSTs are quite rare, occurring in 0.001% of the general population. Approximately 25-50% of MPNSTs are associated with a genetic condition known as neurofibromatosis type 1. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Malignant peripheral nerve sheath tumor	c0751690	30,061	gard	https://rarediseases.info.nih.gov/diseases/10872/malignant-peripheral-nerve-sheath-tumor	2021-01-18T17:59:15	{"mesh": ["D018319"], "orphanet": ["3148"], "synonyms": ["MPNST", "Malignant neurilemmoma", "Malignant neurofibroma", "Malignant schwannoma", "Neurofibrosarcoma", "Neurogenic sarcoma"]}
Thymic endocrine tumor is a rare, malignant, primary thymic neoplasm originating from neuroendocrine cells, presenting as a mass within the anterior mediastinum. Patients typically present with nonspecific symptoms, such as chest pain, cough, shortness of breath, or in some cases, superior vena cava syndrome, although patients could be asymptomatic during the early stages or present with multiple endocrine neoplasia type I. Ectopic production of ACTH and serotonin can lead to Cushing syndrome and carcinoid syndrome, respectively. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Thymic neuroendocrine tumor	None	30,062	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97289	2021-01-23T17:34:53	{"icd-10": ["C37"]}
Normal anion gap acidosis Other namesNon-anion gap acidosis SpecialtyEndocrinology, nephrology Normal anion gap acidosis is an acidosis that is not accompanied by an abnormally increased anion gap. The most common cause of normal anion gap acidosis is diarrhea with a renal tubular acidosis being a distant second. ## Contents * 1 Differential diagnosis * 2 See also * 3 References * 4 External links ## Differential diagnosis[edit] The differential diagnosis of normal anion gap acidosis is relatively short (when compared to the differential diagnosis of acidosis): * Hyperalimentation (e.g. from TPN containing ammonium chloride) * Acetazolamide and other carbonic anhydrase inhibitors * Renal tubular acidosis[1] * Diarrhea: due to a loss of bicarbonate. This is compensated by an increase in chloride concentration, thus leading to a normal anion gap, or hyperchloremic, metabolic acidosis. The pathophysiology of increased chloride concentration is the following: fluid secreted into the gut lumen contains higher amounts of Na+ than Cl−; large losses of these fluids, particularly if volume is replaced with fluids containing equal amounts of Na+ and Cl−, results in a decrease in the plasma Na+ concentration relative to the Cl−concentration. This scenario can be avoided if formulations such as lactated Ringer’s solution are used instead of normal saline to replace GI losses.[2] * Ureteroenteric fistula – an abnormal connection (fistula) between a ureter and the gastrointestinal tract * Pancreaticoduodenal fistula – an abnormal connection between the pancreas and duodenum * Spironolactone * High ostomy output[1] * Hyperparathyroidism – can cause hyperchloremia and increase renal bicarbonate loss, which may result in a normal anion gap metabolic acidosis. Patients with hyperparathyroidism may have a lower than normal pH, slightly decreased PaCO2 due to respiratory compensation, a decreased bicarbonate level, and a normal anion gap.[3] As opposed to high anion gap acidosis (which involves increased organic acid production), normal anion gap acidosis involves either increased production of chloride (hyperchloremic acidosis) or increased excretion of bicarbonate. ## See also[edit] * High anion gap metabolic acidosis ## References[edit] 1. ^ a b "Metabolic Acidosis: Acid-Base Regulation and Disorders: Merck Manual Professional". Retrieved 2008-12-04. 2. ^ Jean-Louis Vincent; Abraham Edward; Kochanek Patrick (8 July 2011). "Acid-base disorders". Textbook of Critical Care. Elsevier. ISBN 143771367X. 3. ^ Coe FL (August 1974). "Magnitude of metabolic acidosis in primary hyperparathyroidism". Arch. Intern. Med. 134 (2): 262–5. doi:10.1001/archinte.1974.00320200072008. PMID 4843192. ## External links[edit] Classification D * ICD-10: E87.2 * ICD-9-CM: 276.2 * DiseasesDB: 29144 * v * t * e Acid–base disorders Acidosis Metabolic * High anion gap * Ketoacidosis * Diabetic ketoacidosis * Alcoholic ketoacidosis * Lactic * Normal anion gap * Hyperchloremic * Renal tubular Respiratory * Respiratory Alkalosis * Metabolic * Contraction alkalosis * Respiratory Other * Mixed disorder of acid-base balance * Acid–base homeostasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Normal anion gap acidosis	None	30,063	wikipedia	https://en.wikipedia.org/wiki/Normal_anion_gap_acidosis	2021-01-18T18:34:41	{"icd-9": ["276.2"], "icd-10": ["E87.2"], "wikidata": ["Q7051791"]}
A rare, genetic renal tubular disease characterized by phosphate loss in the proximal tubule, leading to hypercalciuria and recurrent urolithiasis and/or osteoporosis. ## Epidemiology More than 10 cases have been identified to date. ## Clinical description Disease onset is in adulthood with presentation of nephrolithiasis, renal phosphate wasting and skeletal abnormalities variably including osteopenia, osteoporosis and increased susceptibility to fractures. Cases of spinal deformity have also been described. ## Etiology Heterozygous mutations have been identified in two genes SCL34A1 (5q35), and SLC9A3R1 (17q25.1). SCL34A1 encodes the main sodium-phosphate cotransporter, sodium-dependent phosphate transport protein 2A (NPT2a), located in the apical membrane of renal proximal tubular cells. SLC9A3R1 encodes the Na(+)/H(+) exchange regulatory cofactor (NHERF1), a cytoplasmic protein essential for recruitment of transporter or signaling proteins to the plasma membrane which stabilize NaPi-IIa, the parathyroid hormone (PTH) receptor 1, and phospholipase C at the brush border membrane and creates a platform for PTH signaling to NaPi-IIa . SLC9A3R1 mutations decreases NPT2a expression directly or indirectly via an increase in PTH-responsive downregulation of NaPi-IIa. The decreased serum phosphate levels stimulate 1,25-dihydroxy-Vitamin D synthesis leading to absorptive hypercalciuria, which together with elevated urinary phosphate levels can trigger the formation of calcium-phosphate crystals favoring the development of renal calcifications. ## Diagnostic methods Diagnosis is usually based on clinical features, plasma and urine electrolytes showing hypophosphatemia, hyperphosphaturia, hypercalciuria and increased serum 1,25-dihydroxy-Vitamin D in response to phosphate deprivation. A definitive diagnosis can be achieved by genetic testing. ## Differential diagnosis The differential diagnosis includes other forms of inherited hypophosphatemia such as X-linked hypophosphatemia, autosomal recessive hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria. ## Genetic counseling The pattern of inheritance is autosomal dominant. There is a 50% risk of the disease occurring in a sibling or being transmitted to the offspring of affected individuals. ## Management and treatment Supportive treatment is with phosphate and low‐ dose vitamin D supplementation. ## Prognosis There is no information available on outcomes. * 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	Dominant hypophosphatemia with nephrolithiasis or osteoporosis	c2676786	30,064	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=244305	2021-01-23T17:58:09	{"mesh": ["C567363"], "omim": ["612286", "612287"]}
Spondyloepimetaphyseal dysplasia, matrilin-3 type is characterized by disproportionate early-onset dwarfism, bowing of the lower limbs, short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, lumbar lordosis, hypoplastic iliac bones, flat ovoid vertebral bodies and normal hands. ## Epidemiology The syndrome has been described in a large consanguineous Arab Muslim family. ## Etiology It is caused by mutation in the matrilin-3 gene (MATN3, 2p24-p23) and transmitted in an autosomal recessive manner. * [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spondyloepimetaphyseal dysplasia, matrilin-3 type	c1837481	30,065	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=156728	2021-01-23T17:14:42	{"gard": ["10611"], "mesh": ["C563869"], "omim": ["608728"], "umls": ["C1837481"], "icd-10": ["Q77.7"], "synonyms": ["SEMD, MATN3-related", "SEMD, matrilin-3 type"]}
A number sign (#) is used with this entry because orofaciodigital syndrome I (OFD1) is caused by mutation in the OFD1 gene (300170) on chromosome Xp22. Mutations in the CXORF5 gene also cause Simpson-Golabi-Behmel syndrome type 2 (GBS2; 300209) and Joubert syndrome-10 (JBTS10; 300804). Description Orofaciodigital syndrome type I (OFD1) is characterized by malformations of the face, oral cavity, and digits and is transmitted as an X-linked dominant condition with lethality in males. Thickened alveolar ridges and abnormal dentition, including absent lateral incisors, are additional characteristics of OFD1. The central nervous system may also be involved in as many as 40% of cases. Although these clinical features overlap those reported in other forms of orofaciodigital syndrome, OFD1 can be easily distinguished from among these by its X-linked dominant inheritance pattern and by polycystic kidney disease, which seems to be specific to type I (summary by Ferrante et al., 2001). Since the CXORF5 gene localizes to the centrosome and basal body of primary cilia, OFD1 is considered to be a ciliopathy (Chetty-John et al., 2010). Clinical Features Papillon-Leage and Psaume (1954) described 8 female patients with a hereditary syndrome involving abnormal oral frenula accompanied by alveolar and lingual clefting. They stated that there were only 3 previous reports of the syndrome, and all patients described to date were female. Radiography of the skull in the 8 patients of Papillon-Leage and Psaume (1954) showed asymmetry of the cranial vault, nasal fossae, and sometimes the mandible, with increased interorbital distance and a sella turcica that 'appeared abnormal.' Histologic examination of one of the oral adhesions revealed condensation of the conjunctival tissue around a narrow and deep epithelial invagination. The authors noted that although the phenotype varied in severity, ranging from simple hypertrophy of the frenula with mesialization of the lateral frenula to forms with more marked malpositioning of the teeth, the sites of involvement were always the same. The syndrome was frequently accompanied by a specific constellation of malformations, including cleft lip/palate, aplasia of the alar cartilages, digital malformations such as syndactyly or trident hand, familial tremor, and mental retardation. Papillon-Leage and Psaume (1954) included photographs and detailed clinical descriptions of each of their 8 patients. On the basis of a review of the clinical features in their patients and the patients they identified in the literature, Papillon-Leage and Psaume (1954) expanded the phenotype of OFD I to include a granular appearance of facial skin with diffuse alopecia and dry hair. They suggested that malpositioning of a single canine or premolar with hypertrophy of the lateral frenulum might represent a minimal form of the disorder, and reviewed the embryologic development of the affected region. Gorlin et al. (1961) first reported this condition in the English literature. Clefts of the jaw and tongue in the area of the lateral incisors and canines, other malformations of the face and skull, malformation of the hands (specifically syndactyly, clinodactyly, brachydactyly and occasionally postaxial polydactyly) and mental retardation are features. Others include small nostrils, lobulated tongue with hamartomas, peculiarly irregular and asymmetric clefts of the palate, aberrant hyperplastic oral frenula, transient multiple milia on pinnae, and spotty alopecia. The abnormal oral frenula appear to lead to the clefting of jaw, tongue, and upper lip. Harrod et al. (1976) observed bilateral polycystic kidneys and renal failure in an affected 48-year-old woman and noted other reports of this feature. Donnai et al. (1987) reported a 3-generation family with OFD I in 5 females. Several family members were thought to suffer from autosomal dominant polycystic kidney disease, but examination of the proband led to the correct diagnosis. Connacher et al. (1987) reported a girl with OFD I who, by age 17 years, had established renal failure and bilaterally palpable renal masses. Her mother had less severe OFD I associated with polycystic kidneys, but her renal function was normal. The proband also had agenesis of the corpus callosum demonstrable by computerized tomography. Her IQ was about 70 and she had marked dysarthria and a clumsy gait from early childhood. Anneren et al. (1984) suggested that irregular mineralization of the bones of the hands and feet is an important feature of OFD I distinguishing it from OFD II (252100). Malformations of the brain were described in a severe case of OFD I. Towfighi et al. (1985) found reports of a variety of central nervous system malformations in OFD I and gave a description of the findings in a personally studied case. Goodship et al. (1991) described a 3-generation family in which 3 females showed minor features of OFD I and a severely affected male was born in the third generation. The male showed bilateral duplication of the halluces, a feature considered diagnostic of OFD II, and an atrioventricular septal defect. Heart defects had not previously been reported in OFD I but had been found in OFD II. Goodship et al. (1991) suggested that OFD I and OFD II are not phenotypically distinct and that the case for an autosomal recessive locus deserves reexamination. They urged that when a male neonate has features of OFD, his mother should be examined carefully before it is assumed that he has OFD II. Salinas et al. (1991) reported the variability in 6 affected black U.S. females and in 2 previously reported black patients. Only 2 of the 8 had cleft palate and none had midline of the upper lip; among whites, 80% have cleft palate and 45% have midline cleft of the upper lip. Half of the black patients showed polycystic kidneys. Lipp and Lubit (1990) reported the cases of an affected black mother and daughter followed over many years. Larralde de Luna et al. (1992) described an 11-month-old girl classified as having OFD I, whose features included cleft palate, bifid uvula, lingual cleft, numerous hypertrophic frenula, numerous milia on face, scalp, and ears, frontal bossing, hypertelorism, hypoplasia of the nasal alar cartilages, micrognathia, and bilateral brachydactyly of hands. She also had diffuse, nonscarring alopecia with wiry, dry hair. Radiographic and ultrasound studies were normal, and her psychomotor development was appropriate for her age. ### Clinical Variability Additional clinical forms of orofaciodigital syndrome have been described and numbered OFD2 through OFD11. Gurrieri et al. (2007) referred to 2 further possible forms: OFD12 with myelomeningocele, stenosis of the aqueduct of Sylvius, and cardiac anomalies (Moran-Barroso et al., 1998), and OFD13 with psychiatric symptoms, epilepsy, and brain MRI findings of leukoaraiosis (Degner et al., 1999). Additional forms of OFD (e.g., OFD14-OFD18) were numbered based on genotype. Toriello (2009) noted many phenotypic similarities between OFD syndromes and conditions known as ciliopathies, and suggested that many, if not all, OFD syndromes could be caused by mutations in ciliary proteins. Bruel et al. (2017) reviewed 155 index OFD cases from an international cohort, and noted that although OFD syndromes were initially classified into 13 clinical subtypes, that initial classification appeared to be obsolete given the wide clinical and molecular heterogeneity, as well as multiple overlapping ciliopathies such as Joubert syndrome (see 213300), Meckel syndrome (see 249000), Bardet-Biedl syndrome (see 209900), short-rib polydactyly syndrome (see 208500), and nephronophthisis (see 256100). Bruel et al. (2017) proposed an OFD classification restricted to the 3 most common and well-delineated subtypes, involving the clinical features of kidney disease/corpus callosum agenesis, tibial dysplasia, and molar tooth sign, with further classification based on genotype; however, they stated that detailed classification is extremely complex and of little use in such diseases with high clinical and genetic heterogeneity. Other Features Chetty-John et al. (2010) emphasized that patients with OFD1 can develop fibrocystic disease of the liver and pancreas, in addition to polycystic kidneys. They reported 2 unrelated women with OFD1 diagnosed at birth, who presented as adults with visceral involvement. The first patient presented at age 29 years with severe hypertension and was found to have mildly increased liver enzymes at age 35. Abdominal ultrasound showed multiple cystic intrahepatic bile duct dilatations, pancreatic cysts, and numerous macrocysts in both kidneys. She had no evidence of pancreatic insufficiency. The second patient presented at age 25 years with abdominal pain associated with cystic kidneys, and developed hypertension in her early thirties. At age 37, she had mild hepatomegaly, dilation and beading of the intrahepatic bile ducts, and evidence of hepatic fibrosis. She also had significant proteinuria. In a review of 35 OFD1 patients reported in the literature, Chetty-John et al. (2010) found that all had polycystic kidney disease, 9 (45%) of 20 evaluated had multiple liver macrocysts, and 5 (29%) of 17 evaluated had pancreatic macrocysts. The ages of the patients with cysts ranged from 15 to 38 years. The findings were consistent with OFD1 being a ciliopathy, affecting the development and maintenance of bile ducts and renal tubules. Chetty-John et al. (2010) suggested that patients with OFD1 be routinely monitored for visceral involvement. Inheritance All cases (with the exception mentioned below) are female. A male reported as presumed OFD I syndrome (Kushnick et al., 1963) probably had OFD II or the XXY Klinefelter syndrome. Doege et al. (1964) reported a kindred with 15 affected females. Chromosome studies of 8 of them did not uncover any abnormality. Wahrman et al. (1966) described the condition in an XXY male. This greatly strengthens the idea that inheritance is male-lethal X-linked dominant. Incontinentia pigmenti (308300) and focal dermal hypoplasia (305600) have the same inheritance. Melnick and Shields (1975) suggested that there is some female lethality due to lyonization in heterozygotes. Fuhrmann and Vogel (1960) described cleft lip-palate and syndactyly in a female infant and partial manifestation (syndactyly, finger deformity and split in tip of tongue) in the mother. The lip cleft was median. They cited other cases of this syndrome and suggested autosomal dominant inheritance. Subsequently Fuhrmann et al. (1966) concluded that this was a case of OFD syndrome and that inheritance is X-linked dominant with lethality in males. Vaillaud et al. (1968) described a remarkable pedigree in which 10 females had OFD. The grandmother and 9 of her granddaughters through 3 unaffected sons had OFD. The 9 affected included all daughters of the 3 carrier males. The authors accepted the interpretation of X-linked dominance with lethality in the hemizygous males, which has been applied to previously published pedigrees. In addition, however, to explain the findings in this specific family, they postulated that the OFD gene is on a terminal segment of the X chromosome homologous with a segment of the Y chromosome and that the 3 carrier males had inherited a Y chromosome which in some way masked expression of the OFD gene. Cohen et al. (1981) reported the occurrence of OFD I in a 47,XXX female. Shotelersuk et al. (1999) reported monozygotic twin girls who were discordant for OFD I. Monozygosity was supported by placental pathology (monochorionic diamniotic) and molecular studies which yielded a probability of dizygosity less than 1 x 10(-6). The affected twin had oral cavity abnormalities including median cleft lip, cleft palate, lobulated hamartomatous tongue, aberrant hyperplastic oral frenula, alveolar notches, and absent lateral incisors. Facial manifestations included telecanthus, hypoplastic alae nasi, and transient neonatal facial milia. The patient also had short and deviated fingers with partial cutaneous syndactyly. At 10 years, she had not had central nervous system or kidney problems. X-inactivation study revealed similar X-inactivation patterns in the lymphoblasts of both twins. Shotelersuk et al. (1999) concluded that skewed X-inactivation is an unlikely cause for the discordance, which in their view was more likely due to a postzygotic mutation in the affected twin. Mapping Feather et al. (1997) performed linkage studies in 2 kindreds with OFD I in which the clinical course was dominated by polycystic kidney disease requiring dialysis and transplantation. They were able to map the disorder to a region on the short arm of the X chromosome (Xp22.3-p22.2) spanning 19.8 cM and flanked by crossovers with the markers DXS996 and DX7S105. There was a maximum lod score of 3.32 (theta = 0.0) in an 'affecteds only' analysis using a marker within the KAL1 gene (300836), thereby confirming the location of the gene for OFD1 on Xp/Xp. The remainder of the X chromosome was excluded by recombinants in affected individuals. The importance of the findings included the definitive assignment of this male-lethal disorder to the X chromosome and the mapping of a further locus for human polycystic kidney disease (see also 173900). Furthermore, this mapping suggested that a possible mouse model for OFD1 is the X-linked dominant Xpl mutant, in which polydactyly and renal cystic disease occurs. Xpl maps to the homologous region of the mouse X chromosome (Sweet and Lane, 1980). The full clinical details of one of the families were reported by Feather et al. (1997); the other family had been described by Donnai et al. (1987). By linkage analysis, Malcolm et al. (1997) demonstrated that the OFD1 locus is situated at Xp22.3-p22.2. A maximum lod score of 3.32 at theta = 0.0 was obtained using a marker within the KAL1 gene. They suggested the Xpl mouse as a possible model; that mutation maps to a homologous region of the mouse X chromosome. By linkage studies, Gedeon et al. (1999) narrowed the physical interval containing the OFD1 gene to 12 Mb. They suggested that the flanking markers defined in their study could be used for prenatal diagnosis in female fetuses in families with clinically classic OFD type I. Molecular Genetics To identify the gene responsible for OFD I, Ferrante et al. (2001) analyzed several transcripts mapping to the critical region on Xp22 and found mutations in the CXORF5 gene (see 300170.0001-300170.0003). They analyzed 3 familial and 4 sporadic cases of OFD I. Analysis of the familial cases revealed a missense mutation, a 19-bp deletion, and a single basepair deletion leading to a frameshift. In the sporadic cases, they found a missense (de novo), a nonsense, a splice site, and a frameshift mutation. RNA in situ studies on mouse embryo tissue sections showed that Ofd1 is developmentally regulated and is expressed in all tissues affected in OFD I syndrome. Thus, the involvement of CXORF5 in this specific disorder demonstrates an important role of the gene in human development. In 8 affected female members of 4 Finnish families with OFD1, Rakkolainen et al. (2002) identified heterozygosity for 4 different mutations in the OFD1 gene (see, e.g., 300170.0004 and 300170.0005). In a Japanese woman with sporadic OFD1, Morisawa et al. (2004) identified 2 deletions on the same allele of the OFD1 gene (300170.0006). The most likely cause of the double deletion was considered to be 2 unequal recombinations between homologous sequences. Bruel et al. (2017) reported that 59 (51%) of 115 index OFD cases from an international cohort had causative SNVs or CNVs involving the OFD1 gene. Genotype/Phenotype Correlations Thauvin-Robinet et al. (2006) reported 25 females with OFD I from 16 French and Belgian families. Eleven novel mutations in the CXORF5 gene were identified in 16 patients from 11 families. Renal cysts were associated with splice site mutations, mental retardation was associated with mutations in exons 3, 8, 9, 13, and 16, and tooth abnormalities were associated with mutations in coiled-coil domains. Seven (30%) of 23 patients showed nonrandom X inactivation. Animal Model Ferrante et al. (2009) studied Ofd1 function during zebrafish embryonic development. In wildtype embryos, Ofd1 mRNA was widely expressed and Ofd1-green fluorescent protein (GFP) fusion localized to the centrosome/basal body. Disrupting Ofd1 using antisense morpholinos led to bent body axes, hydrocephalus, and edema. Laterality was randomized in the brain, heart, and viscera, likely a consequence of shorter cilia with disrupted axonemes and perturbed intravesicular fluid flow in Kupffer vesicle. Embryos injected with Ofd1 antisense morpholinos also displayed convergent extension defects, which were enhanced by loss of Slb/Wnt11 (603699) or Tri/Vangl2 (600533), 2 proteins functioning in a noncanonic Wnt/planar cell polarity pathway. Pronephric glomerular midline fusion was compromised in Vangl2 and Ofd1 loss-of-function embryos. The authors concluded that Ofd1 is required for ciliary motility and function in zebrafish, supporting data showing that Ofd1 is essential for primary cilia function in mice. In addition, Ofd1 is important for convergent extension during gastrulation, consistent with data linking primary cilia and noncanonic Wnt/planar cell polarity signaling. Zullo et al. (2010) generated a mouse line with kidney-specific inactivation of the Ofd1 gene, which resulted in a viable animal model for renal cystic disease and progressive impairment of renal function. Primary cilia initially formed and then disappeared after the development of cysts, suggesting that the absence of primary cilia may be a consequence rather than the primary cause of renal cystic disease. Immunofluorescence and Western blot analysis revealed upregulation of the mammalian target of rapamycin (mTOR; 601231) pathway in both dilated and nondilated renal structures. Treatment with rapamycin, a specific inhibitor of the mTOR pathway, resulted in a significant reduction in the number and size of renal cysts and a decrease in the cystic index compared with untreated mutant mice. The authors concluded that dysregulation of this pathway in the model is mTOR-dependent. INHERITANCE \- X-linked dominant GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Face \- Frontal bossing \- Facial asymmetry \- Microretrognathia \- Hypoplasia of the malar bones Ears \- Low-set ears \- Hearing loss Eyes \- Epicanthus \- Hypertelorism \- Telecanthus \- Downslanting palpebral fissures Nose \- Broad nasal bridge \- Hypoplastic alar cartilage Mouth \- Hyperplastic oral frenuli \- Buccal frenuli \- Median cleft lip (in 45% of patients) \- Pseudocleft of the upper lip \- Lobulated tongue (30-45%) \- Bifid tongue (30-45%) \- Tongue nodule \- Cleft palate \- Tongue hamartoma (70%) \- High-arched palate \- Thickened alveolar ridges \- Irregular margin of the lips Teeth \- Dental caries \- Anomalous anterior teeth \- Enamel hypoplasia \- Supernumerary teeth \- Missing teeth CARDIOVASCULAR Heart \- Cardiac anomalies ABDOMEN Liver \- Fibrocystic liver (45%) \- Dilatation and beading of the intrahepatic bile ducts \- Hepatic fibrosis Pancreas \- Pancreatic cysts (29%) GENITOURINARY Internal Genitalia (Female) \- Ovarian cysts Kidneys \- Adult onset polycystic kidney (50%) SKELETAL Hands \- Abnormalities of the fingers (45%) \- Clinodactyly \- Syndactyly \- Brachydactyly \- Polydactyly, preaxial or postaxial (rare) \- X-ray shows irregular pattern of radiolucency and/or spicule-like formation in metacarpals and phalanges Feet \- Abnormalities of the toes (25%) \- Duplication of the hallux \- Polydactyly, preaxial or postaxial (rare) SKIN, NAILS, & HAIR Skin \- Milia of upper face and ears (infancy) \- Dry scalp Hair \- Dry, rough, sparse hair \- Alopecia NEUROLOGIC Central Nervous System \- Variable mental retardation (40%) \- Central nervous system malformations (40%) \- Abnormal gyrations \- Absence of corpus callosum \- Gray matter heterotopias \- Myelomeningocele (rare) \- Stenosis of the aqueduct of Sylvius (rare) \- Hydrocephalus \- Arachnoid cysts \- Cerebellar abnormalities \- Seizures \- Hypothalamic hamartoma \- Porencephaly Behavioral Psychiatric Manifestations \- Major depression (rare) LABORATORY ABNORMALITIES \- Abnormal liver enzymes in those with hepatic cysts or fibrosis \- Proteinuria in those with cystic kidneys MISCELLANEOUS \- Lethal in males MOLECULAR BASIS \- Caused by mutation in the OFD1 protein gene (OFD1, 300170.0001 ) ▲ 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	OROFACIODIGITAL SYNDROME I	c1510460	30,066	omim	https://www.omim.org/entry/311200	2019-09-22T16:17:31	{"doid": ["0060316"], "mesh": ["D009958"], "omim": ["311200"], "orphanet": ["2750"], "synonyms": ["Alternative titles", "ORAL-FACIAL-DIGITAL SYNDROME, TYPE I", "OFDS I", "PAPILLON-LEAGE AND PSAUME SYNDROME"], "genereviews": ["NBK1188"]}
Human disease. The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Hydrops fetalis An ultrasound showing a fetus with Hydrops fetalis SpecialtyObstetrics and gynaecology, hematology, immunology Hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments.[1] By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in the allantoic or amniotic space, respectively.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Immune Pathophysiology * 2.2 Non-immune Pathophysiology * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Locations can include the subcutaneous tissue on the scalp, the pleura (pleural effusion), the pericardium (pericardial effusion) and the abdomen (ascites). Edema is usually seen in the fetal subcutaneous tissue, sometimes leading to spontaneous abortion. It is a prenatal form of heart failure, in which the heart is unable to satisfy demand (in most cases abnormally high) for blood flow.[citation needed] ## Causes[edit] Hydrops fetalis usually stems from fetal anemia, when the heart needs to pump a much greater volume of blood to deliver the same amount of oxygen. This anemia can have either an immune or non-immune cause. Non-immune hydrops can also be unrelated to anemia, for example if a fetal tumor or congenital cystic adenomatoid malformation increases the demand for blood flow.[3] The increased demand for cardiac output leads to heart failure, and corresponding edema. ### Immune Pathophysiology[edit] Rh disease is the only immune cause of hydrops fetalis. Erythroblastosis fetalis, also known as Rh disease, is a hemolytic disease of newborns. Pregnant mothers do not always have the same blood type as their child. During birth or throughout the pregnancy, the mother may be exposed to the infant's blood. In the event of a pregnancy where the fetus has the Rh-D blood antigen and the mother does not, the mother's immune system will respond to the red blood cells as foreign and create antibodies against the Rh-D antigen on the fetal blood cells. Rh disease develops in the event of a second pregnancy where the mother's immune system launches an attack, via IgG, against the infant's Rh-D positive blood cells. The immune response results in hemolysis of fetal red blood cells causing severe anemia.[citation needed] Hemolysis caused by the Rh incompatibility, causes extramedullary hematopoiesis in the fetal liver and bone marrow.[4] The push to make more erythroblasts to help compensate with the hemolysis over works the liver causing hepatomegaly. The resulting liver dysfunction decreases albumin output which in turn decreases oncotic pressure. Consequentially, the decrease in pressure results in overall peripheral edema and ascites.[citation needed] Rh disease is currently an uncommon cause of immune-mediated hydrops fetalis. Due to preventative methods developed in the 1970s, the incidence of Rh disease has markedly declined. Rh disease can be prevented by administration of anti-D IgG (Rho(D) Immune Globulin) injections to RhD-negative mothers during pregnancy and/or within 72 hours of the delivery. However, a small percentage of pregnant mothers are still susceptible to Rh disease even after receiving anti-D IgG (Rho(D) Immune Globulin)[citation needed] ### Non-immune Pathophysiology[edit] Severe anemia leads to hyper dynamic circulation, which means high-output cardiac failure causes the blood to circulate rapidly. The excessive pumping of blood causes the left side of the heart to fail leading to pulmonary edema. The build up of fluid in the lungs increases the pressure in the lungs leading to vasoconstriction. The coupled vasoconstriction and pulmonary hypertension causes the right side of the heart to fail which in turn, increases the venous hydrostatic pressure in the body. The summation of these effects ultimately leads to peripheral edema and ascites. All in all, the left side failure of the heart will lead to pulmonary edema whereas right side failure will lead to peripheral edema and ascites. The non-immune form of hydrops fetalis has many causes including:[5][6] * Iron deficiency anemia * Paroxysmal supraventricular tachycardia resulting in heart failure * Deficiency of the enzyme beta-glucuronidase. This enzyme deficiency is the cause of the lysosomal storage disease called mucopolysaccharidosis type VII. * Congenital disorders of glycosylation * Parvovirus B19 (fifth disease) infection of the pregnant woman (Most Common cause) * Cytomegalovirus in mother * Congenital pulmonary airway malformation (formerly called congenital cystic adenomatoid malformation) * Maternal syphilis and maternal diabetes mellitus * Alpha-thalassemia can also cause hydrops fetalis when all four of the genetic loci for α globin are deleted or affected by mutation. This is termed Hb Barts (consists of y-4 tetramers). * Uncommonly, Niemann-Pick disease Type C (NPC) and Gaucher disease type 2 can present with hydrops fetalis. * Turner syndrome * Tumors,[7] the most common type of fetal tumor being teratoma, particularly a sacrococcygeal teratoma. * Twin-twin transfusion syndrome (TTTS) in pregnancies in which twins share a single placenta (hydrops affects the recipient twin) * Twin anemia-polycythemia sequence (TAPS) * Twin reversed arterial perfusion sequence (TRAPS) * Maternal hyperthyroidism * Fetal cardiac defects and skeletal defects * Noonan syndrome * Mirror syndrome, in which fetal and placental hydrops develops in association with maternal preeclampsia, edema and hypertension * Down syndrome ## Diagnosis[edit] Hydrops fetalis can be diagnosed and monitored by ultrasound scans. An official diagnosis is made by identifying excess serous fluid in at least one space (ascites, pleural effusion, of pericardial effusion) accompanied by skin edema (greater than 5 mm thick). A diagnosis can also be made by identifying excess serous fluid in two potential spaces without accompanying edema. Prenatal ultrasound scanning enables early recognition of hydrops fetalis and has been enhanced with the introduction of MCA Doppler.[5] ## Treatment[edit] The treatment depends on the cause and stage of the pregnancy.[5] * Severely anemic fetuses, including those with Rh disease and alpha thalassemia major, can be treated with blood transfusions while still in the womb. This treatment increases the chance that the fetus will survive until birth.[5][8][9] * Therapy for Cardiac tachyarrhythmia, supraventricular tachycardia, atrial flutter, or atrial fibrillation etiologies are maternal transplacental administration of antiarrhythmic medication(s). This type of treatment is recommended unless the fetus is close to term.[10] * Therapy for Fetal anemia caused by a parvovirus infection or fetomaternal hemorrhage is fetal blood sampling followed by intrauterine transfusion. This treatment at an advanced gestational age poses risks and should not be performed if the risks associated with delivery are considered to be less than those associated with the procedure.[11] * Fetal hydrothorax, chylothorax, or large pleural effusion associated with bronchopulmonary sequestration should be treated using a Fetal needle drainage of effusion or placement of thoracoamniotic shunt. This procedure can be performed prior to delivery if gestational age is advanced.[12] * Hydrops Fetalis resulting from fetal CPAM can be treated using either a fetal needle drainage of effusion or placement of thoracoamniotic shunt or a maternal administration of corticosteroids, betamethasone 12.5 mg IM q24 h × 2 doses or dexamethasone 6.25 mg IM q12 h × 4 doses.[13] * Therapy for hydrops fetalis derived from TTTS or TAPS requires laser ablation of placental anastomoses or selective termination.[14] * Therapy for hydrops fetalis derived from TRAPS requires percutaneous radio frequency ablation.[15] ## See also[edit] * Mirror syndrome ## References[edit] 1. ^ "Hydrops Fetalis: eMedicine Pediatrics: Cardiac Disease and Critical Care Medicine". Retrieved 2010-02-11. 2. ^ Knottenbelt, Derek C. (2003). Equine stud farm medicine and surgery. ISBN 9780702021305. Retrieved 2010-02-11. 3. ^ Isaacs, Hart (January 2008). "Fetal hydrops associated with tumors". American Journal of Perinatology. 25 (1): 43–68. doi:10.1055/s-2007-1004826. ISSN 0735-1631. PMID 18075961. 4. ^ Jagannathan-Bogdan, Madhumita; Zon, Leonard I. (2013-06-15). "Hematopoiesis". Development. 140 (12): 2463–2467. doi:10.1242/dev.083147. ISSN 0950-1991. PMC 3666375. PMID 23715539. 5. ^ a b c d Norton, Mary E.; Chauhan, Suneet P.; Dashe, Jodi S. (February 2015). "Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #7: nonimmune hydrops fetalis". American Journal of Obstetrics and Gynecology. 212 (2): 127–139. doi:10.1016/j.ajog.2014.12.018. ISSN 0002-9378. PMID 25557883. 6. ^ Nassr, Ahmed A.; Ness, Amen; Hosseinzadeh, Pardis; Salmanian, Bahram; Espinoza, Jimmy; Berger, Victoria; Werner, Eleonore; Erfani, Hadi; Welty, Stephen; Bateni, Zhoobin H.; Shamshirsaz, Amir A. (2018). "Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis". Fetal Diagnosis and Therapy. 43 (2): 123–128. doi:10.1159/000475990. ISSN 1015-3837. PMID 28647738. S2CID 3601812. 7. ^ Isaacs, Hart (January 2008). "Fetal Hydrops Associated with Tumors". American Journal of Perinatology. 25 (1): 043–068. doi:10.1055/s-2007-1004826. ISSN 0735-1631. PMID 18075961. 8. ^ Vichinsky, Elliott P. (2009-01-01). "Alpha thalassemia major—new mutations, intrauterine management, and outcomes". Hematology. 2009 (1): 35–41. doi:10.1182/asheducation-2009.1.35. ISSN 1520-4391. PMID 20008180. 9. ^ Derderian, S. Christopher; Jeanty, Cerine; Fleck, Shannon R.; Cheng, Lily S.; Peyvandi, Shabnam; Moon-Grady, Anita J.; Farrell, Jody; Hirose, Shinjiro; Gonzalez, Juan; Keller, Roberta L.; MacKenzie, Tippi C. (January 2015). "The many faces of hydrops". Journal of Pediatric Surgery. 50 (1): 50–54. doi:10.1016/j.jpedsurg.2014.10.027. ISSN 0022-3468. PMC 4315667. PMID 25598092. 10. ^ Donofrio, Mary T.; Moon-Grady, Anita J.; Hornberger, Lisa K.; Copel, Joshua A.; Sklansky, Mark S.; Abuhamad, Alfred; Cuneo, Bettina F.; Huhta, James C.; Jonas, Richard A.; Krishnan, Anita; Lacey, Stephanie (2014-05-27). "Diagnosis and Treatment of Fetal Cardiac Disease: A Scientific Statement From the American Heart Association". Circulation. 129 (21): 2183–2242. doi:10.1161/01.cir.0000437597.44550.5d. ISSN 0009-7322. PMID 24763516. 11. ^ Centers for Disease Control (CDC) (1989-02-17). "Risks associated with human parvovirus B19 infection". MMWR. Morbidity and Mortality Weekly Report. 38 (6): 81–88, 93–97. ISSN 0149-2195. PMID 2536885. 12. ^ Yinon, Y.; Grisaru-Granovsky, S.; Chaddha, V.; Windrim, R.; Seaward, P. G. R.; Kelly, E. N.; Beresovska, O.; Ryan, G. (July 2010). "Perinatal outcome following fetal chest shunt insertion for pleural effusion". Ultrasound in Obstetrics & Gynecology. 36 (1): 58–64. doi:10.1002/uog.7507. ISSN 1469-0705. PMID 20069656. S2CID 206542529. 13. ^ Wilson, R. Douglas; Baxter, Jason K.; Johnson, Mark P.; King, Mary; Kasperski, Stefanie; Crombleholme, Timothy M.; Flake, Alan W.; Hedrick, Holly L.; Howell, Lori J.; Adzick, N. Scott (2004). "Thoracoamniotic Shunts: Fetal Treatment of Pleural Effusions and Congenital Cystic Adenomatoid Malformations". Fetal Diagnosis and Therapy. 19 (5): 413–420. doi:10.1159/000078994. ISSN 1015-3837. PMID 15305098. S2CID 24586927. 14. ^ Society for Maternal-Fetal Medicine; Simpson, Lynn L. (January 2013). "Twin-twin transfusion syndrome". American Journal of Obstetrics and Gynecology. 208 (1): 3–18. doi:10.1016/j.ajog.2012.10.880. ISSN 1097-6868. PMID 23200164. S2CID 78687065. 15. ^ Lee, Hanmin; Bebbington, Michael; Crombleholme, Timothy M.; North American Fetal Therapy Network (2013). "The North American Fetal Therapy Network Registry data on outcomes of radiofrequency ablation for twin-reversed arterial perfusion sequence". Fetal Diagnosis and Therapy. 33 (4): 224–229. doi:10.1159/000343223. ISSN 1421-9964. PMID 23594603. S2CID 12699823. ## External links[edit] Classification D * ICD-10: P56, P83.2 * ICD-9-CM: 773.3, 778.0 * MeSH: D015160 * DiseasesDB: 29715 External resources * MedlinePlus: 007308 * eMedicine: ped/1042 * Patient UK: Hydrops fetalis * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hydrops fetalis	c0020305	30,067	wikipedia	https://en.wikipedia.org/wiki/Hydrops_fetalis	2021-01-18T18:28:44	{"gard": ["2783"], "mesh": ["D015160"], "icd-9": ["773.3", "778.0"], "icd-10": ["P83.2", "P56"], "orphanet": ["1041"], "wikidata": ["Q1679678"]}
A rare, genetic, mixed autoinflammatory and autoimmune syndrome characterized by chronic systemic autoinflammation (presenting as recurrent fever in the neonatal or infantile period) and combined immunodeficiency (manifesting as recurrent viral and invasive bacterial infections). Muscular amylopectinosis may be subclinical or be complicated by myopathy/cardiomyopathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis	c4014605	30,068	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329173	2021-01-23T17:07:58	{"omim": ["615895"]}
That at least one gene concerned with stature is on the Y chromosome is suggested by the comparative heights associated with the XX, XY, and XYY genotypes; that the effect of the Y chromosome on stature is mediated through a mechanism other than androgen is suggested by the tall stature of persons with XY gonadal dysgenesis (400044). It is also argued, from XO and XXY cases, that genes determining slower maturation must be located on the Y chromosome (Tanner et al., 1959). Yamada et al. (1981) found a correlation between the length of the heterochromatic band Yq12 and height; yet complete or almost complete lack of the heterochromatic segment in Amish males of the surname Byler had no effect on stature (or fertility) (Borgaonkar et al., 1969). Ogata and Matsuo (1992) compared the adult height of 27 patients with XY gonadal dysgenesis with 27 patients with XX gonadal dysgenesis (233300). Heights were 171.0 cm and 164.4 cm, respectively; p = less than 0.01. The postulated locus for stature, symbolized STA, was not mapped. From study of tooth size in XO, XX, XY, XYY, XXX and other aneuploid states, Alvesalo and de la Chapelle (1979, 1981) and Alvesalo and Portin (1980) concluded that there are dental growth-promoting factors on both the X and the Y chromosomes. Alvesalo and Portin (1980) suggested that '...the promoting effect of the Y chromosome on tooth growth seems more effective than that of the X chromosome.' This postulated locus on the Y chromosome was earlier symbolized TS; since HGM8 in Helsinki (1985), it has been symbolized GCY for 'growth control Y.' The dental growth factors are thought to be identical to determinants for stature (de la Chapelle, 1994). To localize the growth gene(s) thought to reside on the X chromosome, Ogata et al. (1995) correlated genotype with stature in 13 Japanese and 4 European nonmosaic adult male patients with partial Yq deletion. In 14 patients in whom the region between DYS11 and DYS246 was preserved stature was considered normal: 11 Japanese, 165-180 cm; 3 Europeans, 165-173 cm. The remaining 3 patients in whom this region was deleted had short stature: 2 Japanese, both 159 cm; 1 European, 157 cm. The results suggested that the region defined by DYS11 at interval 5C and by DYS246 at interval 5D may be the critical region for the Y-specific growth gene(s). Kirsch et al. (2000) studied 9 adult patients with Yq- karyotype-chromosomal abnormalities. They demonstrated that all patients with a previously defined pure 46,XYq- karyotype were actually mosaics with cells containing an isodicentric(Y) or ring(Y) chromosome in association with 45,X0 cells. Molecular analyses of chromosomes from patients with interstitial Yq deletions established the critical region for the GCY gene as the 2-Mb interval between DYZ3 and DYS11. To determine whether CYP19 gene (107910) or Y chromosome loci are associated with variation in height, Ellis et al. (2001) performed an association study using common biallelic polymorphisms in CYP19 and the Y chromosome in 413 adult males and 335 females drawn at random from a large population sample. An association between CYP19 and height was found that was more evident in men than in women. An association was also found with the Y chromosome. Additionally, when men were grouped according to haplotypes of the CYP19 and Y chromosome polymorphisms, a difference of 4.2 cm was detected. The authors concluded that in men, genetic variation in CYP19 and on the Y chromosome are involved in determining normal adult height, and that these loci may interact in an additive fashion. Studying 9 individuals with deletions on the Y chromosome, 2 of whom were of short stature, Kirsch et al. (2002) restricted the GCY critical region to a 700-kb region between markers SKY8 and DYS11 (sY83). Growth \- Stature Inheritance \- Y-linked \- ? same as TSY (or GCY) locus ▲ 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	GROWTH CONTROL, Y-CHROMOSOME INFLUENCED	c1868676	30,069	omim	https://www.omim.org/entry/475000	2019-09-22T16:17:00	{"omim": ["475000"], "synonyms": ["Alternative titles", "STATURE", "TOOTH SIZE"]}
Latham and Munro (1937) reported a family in which the parents were second cousins and 5 out of 8 sibs had congenital deafness with myoclonic epilepsy which began at age 10-12 years. Probably no other such families have been reported. See myoclonus, cerebellar ataxia, and deafness (159800). Inheritance \- Autosomal recessive Neuro \- Myoclonus epilepsy \- Seizures Ears \- Congenital hearing loss ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DEAFNESS, CONGENITAL, AND FAMILIAL MYOCLONIC EPILEPSY	c1857348	30,070	omim	https://www.omim.org/entry/220300	2019-09-22T16:28:58	{"mesh": ["C565649"], "omim": ["220300"]}
The jejunal polyps of Peutz-Jeghers syndrome (175200) lead to intussusception. Idiopathic intussusception shows a modest degree of familial aggregation; see review of Jolly et al. (1982), who reported a family in which 5 members in 3 generations had intussusception in infancy. A girl without intussusception developed malignant hyperthermia of a nonrigid type (145600). Her father and a sister had elevated levels of serum creatine kinase. Two older sibs died inexplicably following anesthesia for intussusception surgery and may have had malignant hyperthermia. Jolly et al. (1982) considered the coexistence of these 2 disorders in this family to be happenstance, although clearly each was hereditary. GI \- Intussusception 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	INTUSSUSCEPTION	c0021933	30,071	omim	https://www.omim.org/entry/147710	2019-09-22T16:39:23	{"doid": ["8446"], "mesh": ["D007443"], "omim": ["147710"], "icd-9": ["560.0"], "icd-10": ["K56.1"]}
Erythrokeratodermia with ataxia Other namesGiroux–Barbeau syndrome"[1] Erythrokeratodermia with ataxia is a condition characterized by erythematous, hyperkeratotic plaques with fine, white, attached scales distributed almost symmetrically on the extremities.[1] ## See also[edit] * Hallerman–Streiff 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 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: G11.1 * OMIM: 133190 * MeSH: C535738 C535514, C535738 External resources * Orphanet: 1955 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	Erythrokeratodermia with ataxia	c1851481	30,072	wikipedia	https://en.wikipedia.org/wiki/Erythrokeratodermia_with_ataxia	2021-01-18T18:30:16	{"gard": ["59"], "mesh": ["C535514", "C535738"], "umls": ["C2930921", "C1851481"], "orphanet": ["1955"], "wikidata": ["Q5396477"]}
Compulsive talking (or talkaholism) is talking that goes beyond the bounds of what is considered to be socially acceptable.[1] The main factors in determining if someone is a compulsive talker are talking in a continuous manner or stopping only when the other person starts talking, and others perceiving their talking as a problem. Personality traits that have been positively linked to this compulsion include assertiveness, willingness to communicate, self-perceived communication competence, and neuroticism.[2] Studies have shown that most people who are talkaholics are aware of the amount of talking they do, are unable to stop, or do not see it as a problem.[3] ## Contents * 1 Characteristics * 2 Talkaholic scale * 2.1 Cultural similarities * 3 Consequences and management * 4 See also * 5 References * 6 Further reading * 7 External links ## Characteristics[edit] It has been suggested, through research done by James C. McCroskey and Virginia P. Richmond, that United States society finds talkativeness attractive.[4] It is something which is rewarded and positively correlated with leadership and influence.[1] However, those who compulsively talk are not to be confused with those who are simply highly verbal and vary their quantity of talk. Compulsive talkers are those who are highly verbal in a manner that differs greatly from the norm and is not in the person's best interest.[2] Those who have been characterized as compulsive talkers talk with a greater frequency, dominate conversations, and are less inhibited than others.[1] They have also been found to be more argumentative and have a positive attitude regarding communication.[1] Tendencies towards compulsive talking also are more frequently seen in the personality structure of neurotic psychotic extraverts.[5] It has also been found that talkaholics are never behaviorally shy.[4] ## Talkaholic scale[edit] In 1993 James C. McCroskey and Virginia P. Richmond constructed the Talkaholic Scale, a Likert-type model, to help identify those who are compulsive talkers. A score of 40 or above, which indicates two standard deviations above the norm, would signal someone to be a true talkaholic.[2] ### Cultural similarities[edit] A study done in 1995 of 811 university students in the United States found 5.2% of that population had results indicating they were talkaholics. A similar study from the same year with students from New Zealand found similar results, with 4.7% scoring above 40.[6] ## Consequences and management[edit] Compulsive talking can drive people away, which in turn can leave that person with no social support.[7] Interrupting, another act that is associated with talkaholics, can signal to other people a lack of respect.[7] According to Elizabeth Wagele, an author of best-selling books on personality types, there are different ways to handle compulsive talkers. Such coping techniques include changing the focus of the conversation, taking attention away from the talkaholic, leaving the conversation, and creating a distraction.[8] ## See also[edit] * Chatterbox * Compulsive lying * Compulsive behavior * Conversation ## References[edit] 1. ^ a b c d Bostrom, Robert N.; Grant Harrington, Nancy (1999). "An Exploratory Investigation Of Characteristics Of Compulsive Talkers". Communication Education. 48 (1): 73–80. doi:10.1080/03634529909379154. 2. ^ a b c McCroskey, James C.; Richmond, Virginia P. (1993). "Identifying Compulsive Communicators: The Talkaholic Scale". Communication Research Reports. 10 (2): 107–114. doi:10.1080/08824099309359924. 3. ^ Walther, Joseph B. (Aug 1999). "Communication Addiction Disorder: Concern over Media, Behavior and Effects". Psych Central. Retrieved 21 Oct 2012. 4. ^ a b McCroskey, James C.; Richmond, Virginia P. (1995). "Correlates of Compulsive Communication: Quantitative and Qualitative Characteristics". Communication Quarterly. 43 (1): 39. doi:10.1080/01463379509369954. 5. ^ McCroskey, James C.; Heisel, Alan D.; Richmond, Virginia P. (2001). "Eysenck's BIG THREE And Communication Traits: Three Correlational Studies". Communication Monographs. 68 (4): 360. doi:10.1080/03637750128068. 6. ^ Hackman, Michael Z.; Barthel-Hackman, Tam; Johnson, Craig E. (1995). "Correlates Of Talkaholism In New Zealand: An Intracultural Analysis Of The Compulsive Communication Construct". Communication Research Reports. 12 (1): 5360. doi:10.1080/08824099509362039. 7. ^ a b Chillot, Rick (1997). "Do you talk too much?". Prevention. 49 (10): 118. 8. ^ Wagele, Elizabeth (21 Dec 2010). "The Career Within You. Nine Ways to Cope with Talkaholics". Sussex Publishers. Retrieved 21 Oct 2012. ## Further reading[edit] Books * Axsom JR Compulsive Talkers: Perceptions of Over Talkers Within the Workplace (2006) * Brians P How to overcome compulsive talking (1987) Academic articles * Bostrom RN, Harrington NG An exploratory investigation of characteristics of compulsive talkers Communication Education Volume 48 Issue 1 Pages 73–80 (1999) * Bostrom R, Grant N, Davis W Characteristics of compulsive talkers: A preliminary investigation - Paper presented at the annual meeting of the International Communication Association (1990) ## External links[edit] * Talkaholic Scale (TAS) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Compulsive talking	None	30,073	wikipedia	https://en.wikipedia.org/wiki/Compulsive_talking	2021-01-18T19:07:59	{"wikidata": ["Q5157235"]}
## Description Cisplatin is a highly effective chemotherapeutic agent, but its use is restricted by the high incidence of irreversible ototoxicity associated with it. This ototoxicity causes serious permanent bilateral hearing loss in 10 to 25% of adults receiving the drug, and in up to 60% of children. The consequences of this ototoxicity are particularly serious in children, because even mild hearing loss can compromise language and cognitive development. Cisplatin ototoxicity frequently leads to dose reduction and premature termination of cisplatin treatment, which may affect overall survival rates (summary by Ross et al., 2009). Mapping ### Associations Pending Confirmation Ross et al. (2009) performed association studies for 220 drug metabolism genes in genetic susceptibility to cisplatin-induced hearing loss in children. Ross et al. (2009) genotyped 1,949 SNPs in these candidate genes in an initial cohort of 54 children treated in pediatric oncology units, with replication in a second cohort of 112 children recruited through a national surveillance network for adverse drug reactions in Canada. They identified genetic variants in TPMT (187680) (rs12201199, P value = 0.00022, OR = 17.0, 95% confidence interval 2.3-125.9) and COMT (116790) (rs9332377, P value = 0.00018, OR = 5.5, 95% CI 1.9-15.9) associated with cisplatin-induced hearing loss in children. A Kaplan-Meier graph of cisplatin ototoxicity and number of TPMT and COMT risk alleles showed that an increasing number of TPMT rs12201199 and COMT rs9332377 risk alleles was associated with earlier onset of cisplatin-induced hearing loss (P = 0.00009). An increasing number of these risk alleles was also associated with more severe cisplatin-induced hearing loss (P = 2.7 x 10(-6)). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HEARING LOSS, CISPLATIN-INDUCED, SUSCEPTIBILITY TO	c2750088	30,074	omim	https://www.omim.org/entry/613290	2019-09-22T15:59:04	{"omim": ["613290"], "orphanet": ["240863"], "synonyms": []}
A number sign (#) is used with this entry because this form of hereditary persistence of fetal hemoglobin (HPFH) is caused by heterozygous mutation in the KLF1 gene (600599). For a general phenotypic description and a discussion of other loci that may affect fetal hemoglobin level, see HBFQTL1 (141749). Clinical Features Borg et al. (2010) reported a Maltese family in which 10 individuals had hereditary persistence of fetal hemoglobin (HbF) with levels of HbF ranging from 3.3 to 19.5% of total hemoglobin. The proband presented with mild hypochromic, microcytic red cell indices, but no other phenotypic abnormalities were reported. Inheritance In a Maltese family reported by Borg et al. (2010) with HPFH, the inheritance pattern was autosomal dominant. Mapping By genomewide linkage analysis of a Maltese family with HPFH, Borg et al. (2010) found significant linkage to chromosome 19p13.13 (maximum parametric lod score of 4.2). Molecular Genetics In affected members of a Maltese family with HPFH, Borg et al. (2010) identified a heterozygous mutation in the KLF1 gene (K288X; 600599.0005). Gene expression profiles showed that mutation carriers had decreased expression of the fetal globin repressor BCL11A (606557) and upregulation of the fetal hemoglobin genes HBG1 (142200) and HBG2 (142250). Borg et al. (2010) concluded that haploinsufficiency for KLF1 is a cause of HPFH. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 6	c3150805	30,075	omim	https://www.omim.org/entry/613566	2019-09-22T15:58:16	{"omim": ["613566"], "icd-10": ["D56.4"], "orphanet": ["46532", "251380"], "synonyms": ["HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN, KLF1-RELATED", "HPFH-beta-thalassemia syndrome", "Alternative titles", "HPFH-sickle cell disease syndrome"]}
Benign infantile epilepsy (BIE), also known as benign infantile seizures (BIS), is an epilepsy syndrome of which several forms have been described. The International League Against Epilepsy (ILAE) classify two main forms of the syndrome (familial and nonfamilial)[1] though several other forms have been described in the academic literature. Affected children, who have no other health or developmental problems, develop seizures during infancy. These seizures have focal origin within the brain but may then spread to become generalised seizures. The seizures may occur several times a day, often grouped in clusters over one to three days followed by a gap of one to three months. Treatment with anticonvulsant drugs is not necessary but they are often prescribed and are effective at controlling the seizures. This form of epilepsy resolves after one or two years, and appears to be completely benign. The EEG of these children, between seizures, is normal. The brain appears normal on MRI scan.[2][3] The familial and nonfamilial forms have overlapping features and the presence of a family history of infantile seizures may be the only distinguishing criterion. The nonfamiliar form has a larger range of the onset of seizures: from three to twenty months with most occurring between five and six months. There is no difference between the sexes. With benign familial infantile epilepsy, the seizures onset from four to eight months of age.[2] Some cases of nonfamilial benign infantile seizures occur during a case of mild gastroenteritis. Called benign infantile seizures associated with mild gastroenteritis (BIS with MG), the seizures only occur during this illness and no not recur. Infection with rotavirus is the most common cause.[2] Although children with benign infantile epilepsy typically have a normal EEG between seizures, some infants have been found to have a characteristic abnormal EEG during sleep. Called benign infantile focal epilepsy with midline spikes and waves during sleep, these infants have few seizures and there may often be a family history.[2] ## References[edit] 1. ^ Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr;51(4):676-85. 2010 Feb 26. PMID 20196795. doi:10.1111/j.1528-1167.2010.02522.x. 2. ^ a b c d Vigevano F, Specchio N, Caraballo R, Watanabe K. Benign familial and nonfamilial seizures. In: Dichter MA, Engel J, Pedley TA, Aicardi J, editors. Epilepsy: a comprehensive textbook. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. ch. 227. ISBN 0-7817-5777-0 3. ^ Panayiotopoulos CP. The Epilepsies: Seizures, Syndromes and Management. Oxfordshire: Bladon Medical Publishing; 2005. ch. 6. ISBN 1-904218-34-2. PMID 20821848. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Benign infantile epilepsy	None	30,076	wikipedia	https://en.wikipedia.org/wiki/Benign_infantile_epilepsy	2021-01-18T18:28:43	{"orphanet": ["166311"], "synonyms": [], "wikidata": ["Q4887960"]}
Rectal duplication is a rare congenital anorectal malformation characterized by an egg-like, cystic, mucus-filled mass, composed of intestinal mucosal lining and smooth muscle tissue. Commonly it presents in childhood with symptoms of recurrent urinary tract infections, gastroenteritis, obstruction, perianal sepsis and rectal bleeding. Drainage of mucus or pus from the anus is also a typical presenting sign. The majority are found in the retro-rectal space where they communicate with, or are contiguous to, the rectum. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Rectal duplication	c4511483	30,077	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171220	2021-01-23T17:20:16	{"icd-10": ["Q43.4"]}
Human disease Ross River fever SpecialtyInfectious disease Ross River fever is a mosquito-borne infectious disease caused by infection with the Ross River virus. The illness is typically characterised by flu like symptoms combined with polyarthritis and a rash. The virus is endemic to mainland Australia and Tasmania, the island of New Guinea, Fiji, Samoa, the Cook Islands, New Caledonia and several other islands in the South Pacific.[1] ## Contents * 1 Symptoms and signs * 1.1 Acute illness * 1.2 Chronic illness * 2 Transmission * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Epidemiology * 7 History * 8 Research * 9 References * 10 External links ## Symptoms and signs[edit] Symptoms of the disease vary widely in severity, but major indicators are arthralgia, arthritis, fever, and rash.[2] The incubation period is 7–9 days. About a third of infections are asymptomatic, particularly in children.[3][2] ### Acute illness[edit] About 95% of symptomatic cases report joint pain.[3] This is typically symmetrical and with acute onset, affecting the fingers, toes, ankles, wrists, back, knees and elbows.[2] Fatigue occurs in 90% and fever, myalgia and headache occur in 50–60%.[3] A rash occurs in 50% of patients and is widespread and maculopapular. Lymphadenopathy occurs commonly; pharyngitis and rhinorrhea less frequently. Diarrhea is rare. About 50% of people report needing time off work with the acute illness.[3] If the rash is unnoticed, these symptoms are quite easily mistaken for more common illnesses like influenza or the common cold. Recovery from the flu symptoms is expected within a month, but, because the virus currently cannot be removed once infection has occurred secondary symptoms of joint and muscle inflammation, pain and stiffness can last for many years. Less common manifestations include splenomegaly, hematuria and glomerulonephritis. Headache, neck stiffness, and photophobia may occur. There have been three case reports suggesting meningitis or encephalitis.[citation needed] ### Chronic illness[edit] Reports from the 1980s and 1990s suggested RRV infection was associated with arthralgia, fatigue and depression lasting for years.[2] More recent prospective studies have reported a steady improvement in symptoms over the first few months, with 15–66% of patients having ongoing arthralgia at 3 months. Arthralgias have resolved in the majority by 5–7 months. The incidence of chronic fatigue is 12% at 6 months and 9% at 12 months, similar to Epstein–Barr virus and Q fever.[3] The only significant predictor of the likelihood of developing chronic symptoms is the severity of the acute illness itself. No other aspects of the patient's medical or psychiatric history have been found to be predictive. However, in those with the most persisting symptoms (12 months or more), comorbid rheumatologic conditions and/or depression are frequently observed.[3] ## Transmission[edit] The virus can only be spread by mosquitoes. The main reservoir hosts are kangaroos and wallabies, although horses, possums and possibly birds and flying foxes play a role. Over 30 species have been implicated as possible vectors, but the major species for Ross River fever are Culex annulirostris in inland areas, Aedes vigilax in northern coastal regions and Ae. camptorhynchus in southern coastal regions.[3][2] ## Diagnosis[edit] A blood test is the only way to confirm a case of Ross River fever. Several types of blood tests may be used to examine antibody levels in the blood. Tests may either look for simply elevated antibodies (which indicate some sort of infection), or specific antibodies to the virus.[2] ## Prevention[edit] There is currently no vaccine available. The primary method of disease prevention is minimizing mosquito bites, as the disease is only transmitted by mosquitoes. Typical advice includes use of mosquito repellent and mosquito screens, wearing light coloured clothing, and minimising standing water around homes (e.g. removing Bromeliads, plant pots, garden ponds).[3] Staying indoors during dusk/dawn hours when mosquitos are most active may also be effective. Bush camping is a common precipitant of infection so particular care is required. ## Treatment[edit] Patients are usually managed with simple analgesics, anti-inflammatories, anti-pyretics and rest while the illness runs its course.[1][2] Pentosan polysulfate has also shown recent promise. [4] ## Epidemiology[edit] Most notifications are from Queensland, tropical Western Australia and the Northern Territory. Geographical risk factors include areas of higher rainfall and higher maximal tides.[3] In the tropics, Ross River fever is more prevalent during the summer/autumn "wet season", particularly January—March, when mosquito populations numbers are high. In southern parts of Australia, this time period may shift to earlier in the year during spring/summer. Areas noted of common place contraction of the virus include townships and along the River Murray areas. Backwaters and Lagoons are breeding grounds for mosquitos and local medical treating facilities report higher cases than cities away from the river around the riverina areas.[1][2] Areas near suitable mosquito breeding grounds—marshes, wetlands, waterways and farms with irrigation systems—are high risk areas for outbreaks. As such, the disease is more characteristic of rural and regional areas.[2] Infection is most common in adults aged 25–44 years old, with males and females equally affected.[3] Ross River fever is on the Australian Department of Health and Ageing's list of notifiable diseases.[5] ## History[edit] The first outbreak of RRF was in 1928 in the Hay and Narrandera region in New South Wales, Australia.[3] The virus was first isolated in 1959 from a mosquito trapped along the Ross River in Townsville, Queensland. Since then, outbreaks have occurred in all Australian states, including Tasmania, and metropolitan areas.[3] The largest outbreak occurred in 1979–1980 in the Western Pacific, and affected more than 60,000 people.[3] Before the identification of this infectious agent, the disease was referred to as "epidemic polyarthritis". This term was also used for a similar Australian disease caused by another mosquito-borne virus, Barmah Forest virus.[2] ## Research[edit] The study of RRF has been recently facilitated by the development of a mouse model. Mice infected with RRV develop hind-limb arthritis/arthralgia which is similar to human disease. The disease in mice is characterized by an inflammatory infiltrate including macrophages which are immunopathogenic and exacerbate disease. Furthermore, mice deficient in the C3 protein do not suffer from severe disease following infection.[6] This indicates that an aberrant innate immune response is responsible for severe disease following RRV infection. ## References[edit] 1. ^ a b c Ed Poliness (2006-01-19). "Fact file: Ross River fever". ABC Health & Wellbeing. ABC. Retrieved 2008-10-29. 2. ^ a b c d e f g h i j Russell RC, Doggett SL. "Ross River & Barmah Forest". Department of Medical Entomology, University of Sydney. Retrieved 2008-10-29. 3. ^ a b c d e f g h i j k l m Australian Family Physician: Ross River virus 4. ^ https://www.sbs.com.au/news/breakthrough-in-ross-river-virus-battle 5. ^ "Australian national notifiable diseases list and case definitions". National Notifiable Diseases Surveillance. Australia: Department of Health and Ageing. 2004-03-12. Retrieved 2008-11-29. 6. ^ Morrison TE, Fraser RJ, Smith PN, Mahalingam S, Heise MT (2007). "Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease". J. Virol. 81 (10): 5132–43. doi:10.1128/JVI.02799-06. PMC 1900244. PMID 17314163. ## External links[edit] Classification D * ICD-10: B33.1 * ICD-9-CM: 066.3 * MeSH: D012398 * DiseasesDB: 29866 * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ross River fever	c0035865	30,078	wikipedia	https://en.wikipedia.org/wiki/Ross_River_fever	2021-01-18T18:54:18	{"icd-9": ["066.3"], "icd-10": ["B33.1"], "wikidata": ["Q2744442"]}
A number sign (#) is used with this entry because of evidence that susceptibility to asthma-related traits is associated with specific haplotypes of the prostaglandin D2 receptor (PTGDR; 604687) on chromosome 14. Description Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002; Pillai et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807. Mapping Using 175 extended Icelandic families that included 596 patients with asthma, Hakonarson et al. (2002) performed a genomewide scan with 976 microsatellite markers. The families were identified by cross-matching a list of patients with asthma from the National University Hospital of Iceland with a genealogy database of the entire Icelandic nation. They detected linkage of asthma to chromosome 14q24 with an allele-sharing lod score of 2.66. After they increased the marker density within the locus to an average of 1 microsatellite every 0.2 cM, the lod score rose to 4.00. Hakonarson et al. (2002) designated this locus AS1 and concluded that it represents a major susceptibility gene for asthma. Mansur et al. (1999) and other investigators also found evidence for genetic linkage between IgE phenotypes and 14q markers. The prostanoid DP receptor gene (PTGDR; 604687) is located on 14q22.1 and was shown by Matsuoka et al. (2000) to be a mediator of allergic asthma in mouse experiments. Molecular Genetics Oguma et al. (2004) presented evidence of an association of asthma susceptibility with functional genetic variants of the PTGDR gene. Specific PTGDR haplotypes were significantly associated with a diagnosis of asthma in a large case-control study of whites (P = 0.002) and blacks (P = 0.01). Both whites and blacks who had at least 1 copy of the haplotype with low transcriptional efficiency (604687.0001) had a lower risk of asthma than subjects with no copies of the haplotype. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ASTHMA-RELATED TRAITS, SUSCEPTIBILITY TO, 1	c1846534	30,079	omim	https://www.omim.org/entry/607277	2019-09-22T16:09:28	{"omim": ["607277"], "synonyms": ["Alternative titles", "ASRT1", "AS1"]}
Camptodactyly-taurinuria syndrome is a congenital malformation syndrome characterized by the association of a permanent camptodactyly of the fingers (see this term) with the over excretion of taurine in the urine. Camptodactyly mainly affects the little finger, although any finger may be involved. The disease has been described in 17 affected patients from 4 unrelated families. An autosomal dominant inheritance has been suggested. There have been no further descriptions in the literature since 1966. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Camptodactyly-taurinuria syndrome	c2931681	30,080	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1325	2021-01-23T18:56:31	{"gard": ["1069"], "mesh": ["C537972"], "umls": ["C2931681"], "icd-10": ["Q68.1"], "synonyms": ["Familial streblodactyly with amino-aciduria"]}
Börjeson–Forssman–Lehmann syndrome Other namesIntellectual disability-epilepsy-endocrine disorders syndrome Affected males with BFLS SpecialtyMedical genetics Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare genetic disease that causes intellectual disability, obesity, and growth defects.[1] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] Some symptoms of BFLS are discernible at birth, but they develop over time. Babies with BFLS are born at normal weight but have muscle hypotonia and difficulty feeding. As development progresses, moderate to severe intellectual disability and developmental delays become evident.[2] Beyond intellectual disability, the central nervous system of affected people shows other symptoms, including impaired vision (cataracts and hyperopia, particularly) and nystagmus.[2][1] Vision impairments can develop before age 30.[1] The peripheral nervous system may also be affected by polyneuropathy.[2] Some individuals may have psychiatric problems, most commonly anxiety disorders, depression, behavioral disorders, and hypersexuality.[3] The appearance of affected individuals is characteristic, featuring ptosis, large ears, supraorbital ridge, short stature (in approximately half of affected individuals), gynecomastia, deposits of abdominal fat, swollen cheeks and eyelids, short toes, and tapered fingers. Kyphosis or scoliosis may also be present.[1][2][3] The genitourinary system is also affected by BFLS; the testes of affected children often show hypogonadism and cryptorchidism.[2] Diabetes has co-occurred in several cases.[1] Hearing loss, epilepsy, cleft lip and palate, acute precursor T-cell acute lymphoblastic leukemia, Legg-Calvé-Perthes disease, and hypopituitarism are uncommon.[2][3] People with XX chromosomes are usually carriers of the disease and show few, if any symptoms - if affected, they may have obesity, polyneuropathy, and/or mild intellectual disability.[2] ## Pathophysiology[edit] BFLS is an X-linked recessive genetic disease caused by mutations in PHF6, a gene that encodes a zinc finger protein involved in cell growth.[2][1][3] Point mutations lead to less severe forms of the disease than loss of function mutations or deletions.[3] It is highly expressed during development in the pituitary gland, face, and brain.[2] It occurs primarily in people with XY chromosomes because there is only one copy of the X chromosome present and therefore the only copy of PHF6 is the mutated copy.[2] ## Diagnosis[edit] Definitive diagnosis of BFLS is made with a genetic test, though it can be suspected where there are several people in a family showing the characteristic symptoms. Magnetic resonance imaging, electroencephalography, and electroneuronography can be used to assess the severity of the disease.[2] Mutations in the PHF6 gene have been shown to be the cause of this condition.[4] Other diseases that may need to be distinguished from BFLS include Prader–Willi syndrome, Coffin–Lowry syndrome, Klinefelter syndrome, Wilson–Turner syndrome, Bardet–Biedl syndrome, Smith–Fineman–Myers syndrome (Chudley-Lowry syndrome), and Coffin–Siris syndrome.[1][3] ## Treatment[edit] There is no cure for BFLS, but its symptoms can be managed with surgery and medication. Surgery is used to treat cryptorchidism and cleft palate, whereas medication is used to treat epilepsy that may result from the condition.[2] ## Prognosis[edit] Though affected children can have severe developmental delays, they typically learn to walk between 4 and 6 years old.[2] Intellectual disability in affected individuals does not worsen over time;[3] some affected individuals see their symptoms become less severe.[1] ## Epidemiology[edit] BFLS is extremely rare, with only approximately 50 people diagnosed since its discovery. As with other X-linked diseases, it mostly occurs in males; the few females who have been diagnosed had defects in X-inactivation.[2] ## History[edit] BFLS was described in 1962 by the physicians for whom it is named.[2] ## References[edit] 1. ^ a b c d e f g h "Börjeson-Forssman-Lehman Syndrome - NORD (National Organization for Rare Disorders)". Retrieved 2015-07-25. 2. ^ a b c d e f g h i j k l m n o "Börjeson-Forssman-Lehmann syndrome". www.socialstyrelsen.se. Archived from the original on 2019-04-08. Retrieved 2015-07-24. 3. ^ a b c d e f g "Orphanet: Borjeson Forssman Lehmann syndrome". Orphanet. Retrieved 2015-07-24. 4. ^ Ernst A, Le VQ, Højland AT, Pedersen IS, Sørensen TH, Bjerregaard LL, Lyngbye TJ, Gammelager NM, Krarup H, Petersen MB (2015) The PHF6 mutation c.1A>G; pM1V causes Börjeson-Forsman-Lehmann syndrome in a family with four affected Young boys. Mol Syndromol 6(4):181-186 ## External links[edit] Classification D * ICD-10: Q87.8 * OMIM: 301900 * MeSH: C536575 C536575, C536575 External resources * Orphanet: 127 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Börjeson–Forssman–Lehmann syndrome	c0265339	30,081	wikipedia	https://en.wikipedia.org/wiki/B%C3%B6rjeson%E2%80%93Forssman%E2%80%93Lehmann_syndrome	2021-01-18T18:57:52	{"gard": ["936"], "mesh": ["C536575"], "umls": ["C0265339"], "orphanet": ["127"], "wikidata": ["Q1019940"]}
Sheehan's disease Other namesSimmond's syndrome, postpartum hypopituitarism, postpartum pituitary gland necrosis SpecialtyEndocrinology, obstetrics and gynaecology Sheehan's syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] The various signs and symptoms in Sheehan's syndrome are caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Because the pituitary controls many glands in the endocrine system, partial or complete loss of a variety of functions may result.[2] The most common initial symptoms of Sheehan's syndrome are agalactorrhea (absence of lactation) and/or difficulties with lactation.[3] Many women also report amenorrhea or oligomenorrhea after delivery.[3] In some cases, a woman with Sheehan syndrome is relatively asymptomatic; therefore, the diagnosis would not be made until years later, with features of hypopituitarism.[3] Such features include secondary hypothyroidism (hypothyroidism due to pituitary dysfunction) with tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. Another such feature is secondary adrenal insufficiency (lack of ACTH secretion from the anterior pituitary). In a more chronic case, it is similar to Addison's disease with symptoms including fatigue, weight loss, hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). Such a patient may become acutely exacerbated when her body is stressed by a severe infection or surgery years after her delivery: a condition equivalent with an Addisonian crisis.[3] The symptoms of adrenal crisis should be treated immediately and can be life-threatening.[4] Gonadotropin deficiency will often cause amenorrhea, oligomenorrhea, hot flashes, or decreased libido.[3] Cessation of menses is an important indicator of Gonadotropin deficiency as a result of Sheehan’s syndrome.[5] Growth hormone deficiency causes many vague symptoms including fatigue and decreased muscle mass.[3] Growth-hormone deficiency is the most common symptom of hypopituitarism seen in Sheehan’s syndrome with a 90–100% occurrence seen in the Netherlands, Costa Rica, and Saudi Arabia. In these populations the occurrence of Cortisol, TSH, and gonadotropin deficiencies ranges from 50 to 100%.[5] Hematological changes may occur due to a decrease in erythropoietin synthesis as a result of these cortisol and thyroid hormone decreases.[6] Uncommonly, Sheehan syndrome may also appear acutely after delivery, mainly by hyponatremia.[3] Electrolytic imbalances might result from the increased secretion of ADH, which may be caused by a decrease in blood pressure due to lower glucocorticoid deficiency. There are several possible mechanisms by which hypopituitarism can result in hyponatremia, including decreased free-water clearance by hypothyroidism, direct syndrome of inappropriate antidiuretic hormone (ADH) hypersecretion, decreased free-water clearance by glucocorticoid deficiency (independent of ADH).[3] Serum potassium levels, however, will not change due to Sheehan’s syndrome. This is because potassium levels are primarily regulated independently from the pituitary gland (the renin-angiotensin-aldosterone system begins in the kidney).[7] ## Causes[edit] In the developed world Sheehan’s Syndrome is a rare complication of pregnancy, usually manifesting after excessive blood loss after delivery. The presence of disseminated intravascular coagulation (i.e., in amniotic fluid embolism or HELLP syndrome) also appears to be a factor in its development. A retrospective study in Turkey found that the prevalence of Sheehan’s syndrome was directly proportional to the amount of at-home deliveries each decade.[5] This may be due to previously limited obstetric techniques present in a home environment. For example, an area of improvement in preventing the condition could be the an increase in the efficacy of treatment to hypovolemic shock through blood transfusion.[6] Pituitary necrosis may directly result from a lack of blood flow in the hypophyseal artery as a result of pituitary gland enlargement during pregnancy.[2] One cause of pituitary growth associated with the risk of Sheehan’s syndrome is the hyperplasia of lactotrophs (responsible for prolactin production).[7] Ischemia may occur as a result of vasospasm, thrombosis, or vascular compression sometimes as a result of an increase in the amount of lactotroph cells throughout gestation (contributing to the enlargement of the pituitary gland).[6] Necrosis may occur as a result of severe hypotension or shock due to excessive uterine bleeding following childbirth.[6] Sheehan’s syndrome may occur as a result of the arterial constriction and abnormal hypotension in conjunction with an insufficiency to meet the increased demand in blood supply of the pituitary gland seen during pregnancy.[6] This increased blood-flow and metabolic demand is associated with the previously mentioned hyperplasia of lactotrophs.[7] Some possible predisposing factors to Sheehan’s syndrome may include: inherited or acquired disseminated blood coagulation (DIC), restriction pituitary blood supply, small sella size, vasospasm, or thrombosis.[6] Post-Partum Hemorrhaging (PPH) is believed to be a predictor of Sheehan’s syndrome, so the symptoms of anaemia, obesity, and advanced maternal age may increase the risk of Sheehan Syndrome.[6] Atony of the uterus may be related to PPH that could induce Sheehan’s syndrome. This results in the abnormally prolonged flow of blood to the placenta after delivery.[6] ## Pathophysiology[edit] Sheehan's syndrome is caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. The anterior pituitary is supplied by a low pressure portal venous system.[6] A 1995 study found that 56.2% of patients with diagnosed Sheehan’s syndrome experienced a loss of all pituitary hormones (with the remaining 43.8% having selective pituitary insufficiency). Since the growth hormone-secreting cells are located at the periphery of the pituitary (and are therefore most likely to be affected by ischemia), all of the patients experienced growth hormone deficiency.[5] ## Diagnosis[edit] Hormonal assays are conducted to determine a patient has low levels of T4, TSH, estrogen, gonadotropin, cortisol, and ACTH depending on the extent of necrosis.[5] It might be difficult to detect damage to these hormone pathways if hormone levels are at the borderline of the abnormal range. In this case, stimulation tests will be done to determine if the pituitary is responsive to hypothalamic hormones.[6] For example, to determine deficiencies in cortisol release, synthetic ACTH might be administered, and hormonal assays will be conducted to determine the strength of the response. Additionally, MRI of the pituitary and hypothalamus: this helps to exclude tumor or other pathologies.[citation needed] ## Treatment[edit] Lifelong hormone replacement therapy for the hormones that are missing.[8] This may involve treatment with glucocorticoids. After hormone profiling, treatment with cortisol, ACTH, thyroid hormones, gonadotropins, and prolactin as seen in cases of hypopituitarism may occur.[8] ## Epidemiology[edit] In a study of 1,034 symptomatic adults, Sheehan’s syndrome was found to be the sixth-most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor).[5] Sheehan syndrome is more prevalent in developing countries than developed countries.[6] Additionally, it was found that the majority of women who experienced Sheehan syndrome gave birth at home rather than in a hospital.[6] ## History[edit] The specific association with postpartum shock or hemorrhage was described in 1937 by the British pathologist Harold Leeming Sheehan (1900–1988).[9] The initial distinction was made in the research article “Post-Partum Necrosis of the Anterior Pituitary”.[10] In his research, Dr. Sheehan reviewed (through autopsy) the effects of pituitary necrosis on 12 cases of patient’s that experienced postpartum necrosis.[10] He observed cases where lesions and death occurred during or after pregnancy, as well as cases where death occurred in the late stage of necrosis (years later). This started the initial distinction of Sheehan’s syndrome from Simmonds’ disease (also known as hypopituitarism). Dr. Sheehan noted that significant features of these patient cases was hemorrhaging, which in his experience was most commonly caused by either: placenta Previa (low placenta), uterine rupture, cervical or uterine tears, post-partum atony, or retained placenta. Simmonds' disease, however, occurs in either sex due to causes unrelated to pregnancy.[6] However, in his 1939 publication: “Simmonds’ Disease due to Post-partum Necrosis of the Anterior Pituitary”, Dr. Sheehan displays post-partum necrosis as a cause of Simmonds’ disease, thus establishing the relationship between the two conditions.[11] According to Sheehan in 1939 approximately 41% of survivors of severe postpartum hemorrhage (PPH) and/or hypovolemic shock experienced severe or partial hypopituitarism.[6] ## References[edit] 1. ^ Kaufman MS, Stead LG (2011). First aid for the obstetrics & gynecology clerkship. McGraw-Hill Professional. ISBN 9780071634199. OCLC 768527672. 2. ^ a b Keleştimur F (December 2003). "Sheehan's Syndrome". Pituitary. 6 (4): 181–188. doi:10.1023/B:PITU.0000023425.20854.8e. ISSN 1573-7403. PMID 15237929. S2CID 25547320. 3. ^ a b c d e f g h Schrager S, Sabo L (September 2001). "Sheehan syndrome: a rare complication of postpartum hemorrhage". The Journal of the American Board of Family Practice. 14 (5): 389–91. PMID 11572546. 4. ^ "Addison's disease - Symptoms and causes". Mayo Clinic. Retrieved 2019-04-29. 5. ^ a b c d e f Shivaprasad C (September 2011). "Sheehan's syndrome: Newer advances". Indian Journal of Endocrinology and Metabolism. 15 Suppl 3 (7): S203-7. doi:10.4103/2230-8210.84869. PMC 3183525. PMID 22029025. 6. ^ a b c d e f g h i j k l m n Karaca Z, Laway BA, Dokmetas HS, Atmaca H, Kelestimur F (December 2016). "Sheehan syndrome". Nature Reviews. Disease Primers. 2: 16092. doi:10.1038/nrdp.2016.92. PMID 28004764. S2CID 36776064. 7. ^ a b c Aiguo W, Guangren D (July 2006). "PMID Observer Design of Descriptor Linear Systems". 2007 Chinese Control Conference. IEEE: 161–165. doi:10.1109/chicc.2006.4347343. ISBN 9787811240559. S2CID 72187. 8. ^ a b Errarhay S, Kamaoui I, Bouchikhi C, Châara H, Bouguern H, Tizniti S, Melhouf A, Banani A (June 2009). "Sheehan's Syndrome A Case Report and Literature Review". The Libyan Journal of Medicine. 4 (2): 81–2. doi:10.4176/081201. PMC 3066722. PMID 21483515. 9. ^ Sheehan HL (January 1965). "The Repair of Post-Partum Necrosis of the Anterior Lobe of the Pituitary Gland". Acta Endocrinologica. 48 (1): 40–60. doi:10.1530/acta.0.0480040. PMID 14254773. 10. ^ a b Sheehan HL (1937). "Post-partum necrosis of the anterior pituitary". The Journal of Pathology and Bacteriology. 45 (1): 189–214. doi:10.1002/path.1700450118. ISSN 0368-3494. 11. ^ Cooke RT (October 1945). "Simmonds's Disease due to Post-partum Necrosis of Anterior Pituitary". British Medical Journal. 2 (4423): 493–4. doi:10.1093/oxfordjournals.qjmed.a069138. PMC 2059949. PMID 20786336. ## External links[edit] Classification D * ICD-10: E23.0 * ICD-9-CM: 253.2 * MeSH: D007018 * DiseasesDB: 11998 External resources * MedlinePlus: 001175 * eMedicine: med/1914 * v * t * e Pituitary disease Hyperpituitarism Anterior * Acromegaly * Hyperprolactinaemia * Pituitary ACTH hypersecretion Posterior * SIADH General * Nelson's syndrome * Hypophysitis Hypopituitarism Anterior * Kallmann syndrome * Growth hormone deficiency * Hypoprolactinemia * ACTH deficiency/Secondary adrenal insufficiency * GnRH insensitivity * FSH insensitivity * LH/hCG insensitivity Posterior Neurogenic diabetes insipidus General * Empty sella syndrome * Pituitary apoplexy * Sheehan's syndrome * Lymphocytic hypophysitis * Pituitary adenoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Sheehan's syndrome	c0242342	30,082	wikipedia	https://en.wikipedia.org/wiki/Sheehan%27s_syndrome	2021-01-18T19:03:27	{"gard": ["7630"], "mesh": ["D007018"], "umls": ["C0242342"], "icd-9": ["253.2"], "orphanet": ["91355"], "wikidata": ["Q535876"]}
Type II xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the deficiency of both xanthine dehydrogenase and aldehyde oxidase, leading to the formation of urinary xanthine urolithiasis and leading, in some patients, to kidney failure. Other less common manifestations include arthropathy, myopathy and duodenal ulcer, while some patients remain asymptomatic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Xanthinuria type II	c1863688	30,083	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93602	2021-01-23T19:12:12	{"gard": ["5620"], "mesh": ["C566358"], "omim": ["603592"], "umls": ["C1863688"], "icd-10": ["E79.8"], "synonyms": ["XDH and AOX dual deficiency", "Xanthine dehydrogenase and xanthine aldehyde oxidase dual deficiency"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive complete congenital stationary night blindness-1C can be caused by homozygous or compound heterozygous mutation in the TRPM1 gene (603576) on chromosome 15q13-q14. For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500). Clinical Features Li et al. (2009) studied 3 families with complete congenital stationary night blindness (CSNB), 1 of South Asian ethnicity and 2 of Caucasian European descent, in which affected members had myopia, reduced central vision, nystagmus, and electroretinographic (ERG) evidence of ON bipolar cell dysfunction typical of complete CSNB. None had abnormalities of skin pigmentation, although other skin conditions were reported, including dry skin requiring emollients, a history of treatment for 'eczema,' and an uncharacterized condition 'similar to epidermolysis bullosa simplex.' Mapping In a consanguineous family of South Asian ethnicity with complete CSNB, Li et al. (2009) performed genomewide linkage analysis and identified a 15.9-Mb candidate region on proximal chromosome 15q, flanked by the polymorphisms rs2090622 and rs10518928. Molecular Genetics In a consanguineous family of South Asian ethnicity with complete CSNB, Li et al. (2009) identified homozygosity for a splice site mutation (603576.0001) in the TRPM1 gene in the affected mother; the father was heterozygous for the mutation. Li et al. (2009) screened the TRPM1 gene in 9 families that were negative for mutation in the NYX (300278) and GRM6 (604096) genes and identified compound heterozygosity for TRPM1 mutations in 2 families of Caucasian European descent (see, e.g., 603576.0002-603576.0003). None of the mutations were found in 192 control individuals. Li et al. (2009) noted that in their study, 7 CSNB families had no mutations in the NYX, GRM6, or TRPM1 genes, indicating possible further genetic heterogeneity. Audo et al. (2009) analyzed the TRPM1 gene in 38 clinically diagnosed CSNB patients and identified homozygosity or compound heterozygosity for 14 causative mutations in 10 unrelated patients, including missense, splice site, deletion, and nonsense mutations (see, e.g., 603576.0004-603576.0005). In 6 of 8 female probands of European ancestry with complete CSNB, who were negative for mutation in GRM6 and NYX, van Genderen et al. (2009) identified mutations in TRPM1 (see, e.g., 603576.0005-603576.0007). The authors noted that the ERG responses of all 6 TRPM1 probands were identical to those of CSNB patients with NYX mutations, i.e., responses at low intensities were completely absent, whereas they were similar to normal responses at higher intensities, revealing the complete absence of the primary rod pathway and mildly reduced activity of the secondary rod pathway. CSNB patients with mutations in the GRM6 gene (CSNB1B; 257270), however, had been shown to have responses at all intensities that were markedly dissimilar in phase compared to normal responses (Zeitz et al., 2005); van Genderen et al. (2009) concluded that detailed ERG analysis is an effective way to discriminate among patients with mutations in TRPM1 and GRM6. Nakamura et al. (2010) analyzed the TRPM1 gene in 4 unrelated Japanese patients with CSNB who were known to be negative for mutation in the NYX and GRM6 genes, and identified compound heterozygosity for 5 different mutations in 3 patients (see, e.g., 603576.0008-603576.0010). Fundus examination of the patients, who had night blindness from early childhood, revealed no abnormalities other than myopic changes; the single bright-flash, mixed rod-cone ERG showed a negative-type configuration, with a reduced normal a-wave and a significantly reduced b-wave. Animal Model Witzel et al. (1978) described ERG studies in nyctalopic Appaloosa horses which showed photopic and scotopic abnormalities similar to those in humans with congenital stationary night blindness (CSNB) of the Schubert-Bornschein type. Photopic abnormalities consisted of reduced b-wave amplitudes and slower-than-normal b-wave implicit time; dark-adapted ERGs showed a simple negative potential, with a nonrecordable scotopic b-wave but a normal c-wave. Histologic studies revealed no structural abnormalities to account for the functional defect. The Appaloosa coat spotting pattern in horses is caused by a single incomplete dominant gene, designated 'LP,' homozygosity for which is directly associated with CSNB in Appaloosa horses. Bellone et al. (2008) analyzed the relative expression of 5 candidate genes located in the 6-cM LP region on horse chromosome 1 and found markedly reduced expression of TRPM1 in the retina and pigmented and unpigmented skin of homozygous LP/LP Appaloosa horses compared to non-Appaloosa lp/lp horses (p = 0.001 for all). Bellone et al. (2008) concluded that decreased expression of TRPM1 in the eye and skin might alter bipolar cell signaling as well as melanocyte function, thus causing both CSNB and LP in horses. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1C	c0339535	30,084	omim	https://www.omim.org/entry/613216	2019-09-22T15:59:21	{"doid": ["0110867"], "mesh": ["C536122"], "omim": ["613216"], "orphanet": ["215"], "synonyms": ["Alternative titles", "CSNB, COMPLETE, AUTOSOMAL RECESSIVE"]}
A rare syndrome syndrome characterized by neonatal blisters and milia (small white papules, especially on the face) and congenital absence of dermatoglyphics on the hands and feet. It has been reported in two kindreds (one of which contained 13 affected individuals spanning three generations) and in an unrelated individual. Some affected patients also showed bilateral partial flexion contractures of the fingers and toes, and webbing of the toes. The syndrome is inherited as an autosomal dominant trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Absence of fingerprints-congenital milia syndrome	c0406707	30,085	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1658	2021-01-23T19:08:40	{"gard": ["2336"], "mesh": ["C537659"], "omim": ["129200"], "umls": ["C0406707"], "icd-10": ["Q82.8"], "synonyms": ["Absence of dermatoglyphics-congenital milia syndrome", "Baird syndrome", "Basan-Baird syndrome"]}
Juvenile cataract - microcornea - renal glucosuria is an extremely rare autosomal dominant association reported in a single Swiss family and characterized clinically by juvenile cataract associated with bilateral microcornea, and renal glucosuria without other renal tubular defects. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Juvenile cataract-microcornea-renal glucosuria syndrome	c4310806	30,086	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247794	2021-01-23T18:22:48	{"omim": ["612018"], "synonyms": ["Juvenile cataract-microcornea-renal glycosuria syndrome"]}
## Description Cronkhite-Canada syndrome is characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. It is associated with high morbidity (summary by Sweetser et al., 2012). Clinical Features Cronkhite and Canada (1955) described 2 unrelated patients with a syndrome of gastrointestinal polyposis, skin hyperpigmentation, alopecia, onychodystrophy, and diarrhea. Another patient with similar features was reported by Jarnum and Jensen (1966). Manousos and Webster (1966) reported the fourth patient. All 4 cases were sporadic and all patients were adults. The prognosis is poor. The pigmentation is diffuse rather than spotted as in the Peutz-Jeghers syndrome (175200). Sweetser et al. (2012) described 14 consecutive cases of Cronkhite-Canada syndrome seen at the Mayo Clinic on whom tissue and follow-up were available. Diffuse polyposis throughout the gastrointestinal tract with esophageal sparing and ectodermal abnormalities (alopecia, onychodystrophy, and skin hyperpigmentation) were seen in most patients. Laboratory findings suggested that malabsorption with hypoalbuminemia was nearly universal. A significant level of IgG4 in steroid-responsive polypoid tissue in patients suggested an autoimmune inflammatory process. Inheritance Sweetser et al. (2012) stated that 'Cronkhite-Canada syndrome...is a noninherited condition.' INHERITANCE \- Isolated cases GROWTH Weight \- Cachexia HEAD & NECK Eyes \- Cataracts Mouth \- Xerostomia \- Glossitis \- Diminution of sense of taste ABDOMEN Gastrointestinal \- Gastrointestinal hamartomatous polyps (stomach, small bowel, colon) \- Vomiting \- Abdominal pain \- Diarrhea \- Protein-losing enteropathy \- Malabsorption \- Hematochezia \- Anorexia SKELETAL Hands \- Clubbing of fingers SKIN, NAILS, & HAIR Skin \- Skin hyperpigmentation Nails \- Onychodystrophy Hair \- Alopecia NEUROLOGIC Central Nervous System \- Paresthesia \- Peripheral neuropathy \- Weakness HEMATOLOGY \- Anemia \- Thromboembolism NEOPLASIA \- Gastrointestinal carcinoma LABORATORY ABNORMALITIES \- Hypocalcemia \- Hypomagnesemia \- Hypokalemia MISCELLANEOUS \- Typical onset in adulthood ▲ 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	POLYPOSIS, SKIN PIGMENTATION, ALOPECIA, AND FINGERNAIL CHANGES	c0282207	30,087	omim	https://www.omim.org/entry/175500	2019-09-22T16:35:58	{"doid": ["6225"], "mesh": ["D044483"], "omim": ["175500"], "orphanet": ["2930"], "synonyms": ["Alternative titles", "CRONKHITE-CANADA SYNDROME"]}
Extraskeletal chondroma Other namesChondroma of soft parts Chondroma of the soft parts located in the little toe. SpecialtyDermatology Extraskeletal chondroma is a cutaneous condition, a rare benign tumor of mature cartilage.[1] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. * v * t * e Tumours of bone and cartilage Diaphysis * Multiple myeloma * Epithelia * Adamantinoma * Primitive neuroectodermal tumor * Ewing family * Ewing's sarcoma Metaphysis Osteoblast * Osteoid osteoma * Osteoblastoma * Osteoma/osteosarcoma Chondroblast * Chondroma/ecchondroma/enchondroma * Enchondromatosis * Extraskeletal chondroma * Chondrosarcoma * Mesenchymal chondrosarcoma * Myxoid chondrosarcoma * Osteochondroma * Osteochondromatosis * Chondromyxoid fibroma Fibrous * Ossifying fibroma * Fibrosarcoma Epiphysis Chondroblast * Chondroblastoma Myeloid * Giant-cell tumor of bone Other Notochord * Chordoma * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline 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	Extraskeletal chondroma	c1275277	30,088	wikipedia	https://en.wikipedia.org/wiki/Extraskeletal_chondroma	2021-01-18T18:46:13	{"umls": ["C1275277"], "wikidata": ["Q5422255"]}
This article is about the poisoning victim. For other uses, see Zhu Ling (disambiguation). In this Chinese name, the family name is Zhu (朱). Thallium Poisoning of Zhu Ling LocationTsinghua University, Beijing Date? – April 1995 VictimZhu Ling Zhu Ling (Chinese: 朱令; pinyin: Zhū Lìng, born 1973) photo is best known as the victim of an unsolved 1995 thallium poisoning case in Beijing, China. Her symptoms were posted to the Internet via a Usenet newsgroup by her friend from Peking University, Bei Zhicheng, and were subsequently proven to be caused by thallium poisoning. Her case was then reviewed by physicians in many different countries who examined her symptoms and made suggestions as to diagnoses and treatment. This effort was recognized as the first large scale tele-medicine trial.[1] Her life was ultimately saved, but she suffered serious neurological damage and permanent physical impairment. This case drew great attention in the Chinese media, because the victim and the suspect were living in the same dormitory[citation needed] in the most prestigious university of China, and the case was never solved. Internet discussion of the crime has continued since then and became a hot topic on major online Chinese communities very frequently as a high-profile cold case. ## Contents * 1 Poisoning case * 2 Diagnosis via Internet * 3 Hair Analysis * 4 Police investigation * 5 Suspect * 5.1 2013 White House Petition * 6 Symbolic significance * 7 Notes * 8 References * 9 External links ## Poisoning case[edit] In 1994, Zhu Ling was a sophomore in Class Wuhua2 (Class 2 majored in physical chemistry) at Tsinghua University in Beijing. Classmates described her as attractive, intelligent, and talented, with an interest in music. She began to show strange and debilitating symptoms at the end of 1994, when she reported experiencing acute stomach pain, along with extensive hair loss. Following her hospitalization at TongRen Hospital, her condition gradually improved and she was allowed to return to school. The following March, however, her old symptoms returned worse than before, this time accompanied by pain in her legs, loss of muscular eye control, and partial facial paralysis. Unable to breathe on her own, she was placed on a respirator. One physician at Peking Union Medical College Hospital (PUMCH), Dr. Li Shun-wei, reported having diagnosed a similar poisoning case in the 1960s and strongly suspected that Zhu Ling's symptoms were caused by thallium poisoning. However, Zhu Ling denied that she had had any contact with thallium in class, a claim which was confirmed by her university's chemistry department. As a result, her doctors ruled out thallium poisoning as a potential cause. Instead, she was diagnosed with and treated for Guillain–Barré syndrome. Her condition deteriorated rapidly. ## Diagnosis via Internet[edit] Frustrated with local physicians' inability to help Zhu Ling, her friends Cai Quanqing and Bei Zhicheng, undergraduate students in Peking University, posted an "SOS" letter on a number of Internet usenet groups on April 10, 1995, describing their friend's symptoms and asking for help with a diagnosis.[2][3] It was remarkable that by 1995 only a few research institutes in China had Internet connections, including Cai's advisor. Responses began pouring in within a matter of hours,[4] and news reports hailed the event as a milestone in remote diagnosis by Internet, especially in China. Of the more than 1,500 responses which Zhu Ling's friends received, roughly one-third proposed that she was suffering from thallium poisoning, the common antidote for which is known as Prussian blue. Subsequent tests confirmed that Zhu Ling had extraordinarily high levels of thallium in her body, about 10,000 times more than normal people.[5] Doctors were able to administer the antidote, Prussian blue in time to save her life, but she sustained serious permanent neurological damage. While she has recovered the ability to breathe on her own, she still cannot speak and remains largely paralyzed and almost blind, with severely reduced mental function. In addition, she has contracted Hepatitis C from a tainted blood transfusion. ## Hair Analysis[edit] Zhu Ling’s parents have collected a small number of hairs from a blanket used by her during the poisoning period (1994-1995) and stored them in a plastic bag since. These samples were obtained by Min He, who, through collaboration with Richard Ash at the University of Maryland, reconstituted the original poisoning process using LA-ICP-MS technique.Inductively coupled plasma mass spectrometry The results were published in Forensic Science International in 2018.[1] In summary, it appears that Zhu Ling had suffered ~4 months of repeated exposure to thallium with increased doses and frequency towards the end, as well as ~2 weeks of constant ingestions of large doses of thallium accompanied by elevated amount of lead. The overall thallium distribution profiles in the analyzed hairs suggested both chronic and acute thallium exposures that correlated well with the sequential presentation of a plethora of symptoms originally experienced by Zhu Ling. Aligning the time-resolved thallium peaks in the hair with her symptoms also provided clues on possible routes of exposure at different poisoning stages. ## Police investigation[edit] The police began investigating the case in May 1995. It was not until January 2006 that police finally revealed to the media that their initial investigations had yielded a possible suspect. No explanation was given for the delay in releasing this information, and no one has yet been formally charged in connection with the case. The primary investigator, Li Shusen, told a correspondent from Southern People Weekly in a January 2006 phone interview that investigators have in fact reached some important conclusions regarding the case, but that the information is too sensitive to be released to the public at this time. ## Suspect[edit] The main suspect after police investigation is Sun Wei (孙维) (born (1973-08-20)August 20, 1973), who was Zhu Ling's classmate and roommate in Tsinghua University from 1992 to 1997. Tsinghua University also said Sun Wei was the only student who would have had official access to thallium compound among the students with close relationship to Zhu Ling, according to Zhu Ling's lawyer, Zhang Jie.[6] The authorities refused to release the results of their investigation to Zhu Ling's parents after they appealed.[7] However, Tsinghua University denied to issue Sun Wei's B.S. certificate and refused to provide her document needed to get a passport or visa in 1997. It is believed Sun Wei has changed her name to Sun Shiyan (孙释颜). The case began to draw extensive public attention near the end of 2005, after an ID named "skyoneline" posted on one of the largest Chinese online bulletin boards, Tianya Club, again questioning the innocence of the suspect and her family's role in blocking investigation and prosecution of the case.[8] In response, after over ten years of silence, on December 30, 2005, the main suspect Sun Wei released a statement proclaiming her innocence, which was confirmed by a weekly newspaper, Qingnian Zhoumo after interviewing Sun Wei's father in 2006.[9][10] According to the statement, the suspect was identified as the only student with official access to thallium in her experiment for undergraduate research. She was detained by the police department on April 2, 1997, and signed a paper acknowledging she was a suspect. Sun Wei's family retrieved her from the police after eight hours of interrogation. In her statement, she also claimed that, according to the law, she was cleared as a suspect in August 1998. However, in a Morning News Post report dated March 2006, Zhu Ling's lawyer, Zhang Jie said of the suspect, "She was only exempted from the compulsory measure that she was subjected to as a suspect at that time, but not excluded from suspicion." Internet discussion of the crime continues since then and became hot topic on major online Chinese communities frequently as a high-profile unsolved case. A hacker who claimed he had hacked into the email account of one of Sun Wei's classmates, revealed communications purporting to be between Sun and several of her classmates, showing Sun Wei was guiding them how to post on forums to declare her innocence and they were preparing for Sun's statement in 2005.[11][12] Among the Internet users in the discussion, many people speculate that the main suspect has not been charged due to her family connections. Sun Wei's grandfather is Sun Yueqi (孙越崎) who was an important member of Chinese People's Political Consultative Conference as a senior leader of Revolutionary Committee of the Chinese Kuomintang and her first cousin once removed, Sun Fuling was deputy mayor of Beijing from 1983 to 1993 and Vice Chairperson of the Chinese People's Political Consultative Conference from 1998 to 2003. ### 2013 White House Petition[edit] An online White House Petition on the whitehouse.gov website was created on May 3, 2013, demanding investigation on the major suspect who was believed living in the US at the time. The number of the signatures reached 100,000 goal three days later after it was created. This online campaign also drew great attention from US and Chinese mainstream media, about Zhu Ling's family and the cold case.[13][14][15] On July 28, 2015, the White House declined comment on the petition, saying "Zhu Ling's poisoning in 1995 was a tragedy. No young person deserves to suffer as she has, and we can understand the heartbreak of those close to her. We decline, however, to comment on the specific request in your petition. As the We the People Terms of Participation explain, to "avoid the appearance of improper influence, the White House may decline to address certain procurement, law enforcement, adjudicatory, or similar matters properly within the jurisdiction of federal departments or agencies, federal courts, or state and local government." ## Symbolic significance[edit] Widespread awareness by the Chinese public and cynicism regarding the matter and the alleged whitewashing of it pose public relations problems for the government of China. Information regarding the matter is too widespread to suppress, but, at the same time, evidence adequate to establish the guilt or innocence of the primary suspect is probably unavailable. Thus the matter serves as a vehicle for expression of public dissatisfaction with corruption and abuse of power by the political elite associated with the regime.[16] ## Notes[edit] 1. ^ "Loonen J. (Rosas C&M, The Netherlands)Telemedicine--Telework in medicine and business" (PDF). TELESOL Newsletter Volume 2, pages 9–11. Archived from the original (PDF) on 2006-07-21. 2. ^ Cai Quanqing (1995-04-10). "For Help". Newsgroup: sci.med. Retrieved 2018-12-25. 3. ^ Cai Quanqing (1995-04-11). "Urgent!!! Need diagnostic advice for sick friend". Newsgroup: sci.med. Retrieved 2018-12-25. 4. ^ Li, Xin; Aldis, John W. "Diagnosis through Internet". The First Large-Scale International Telemedicine Trial to China: ZHU Ling's Case. Archived from the original on 1998-12-07. Retrieved 2018-12-25. 5. ^ "Documentary: Zhu Ling's twelve years". CCTV. 6. ^ Zhang Jie (April 20, 2013). "Complete analysis of testimony in Zhu Ling's poisoning case" (in Chinese). 7. ^ "Zhu Ling's case unsolved after 19 years" (in Chinese). the Beijing News. April 20, 2013. 8. ^ "天妒红颜：十年前的清华女生被毒事件". skyoneline. Retrieved April 19, 2013. 9. ^ "孙维的声明－－驳斥朱令铊中毒案件引发的谣言". Sun Wei Statement. Retrieved April 19, 2013. 10. ^ "我比任何人都想将真凶绳之于法". Southern Metropolis Daily. Archived from the original on 2013-04-22. 11. ^ "I want to restart Zhu Ling's case" (in Chinese). Southern Metropolis Daily. April 20, 2013. p. AA32. Archived from the original on April 27, 2013. 12. ^ "Sun Wei's guide for her friends revealed by hacked E-mail". 13. ^ Steven Jiang. "Old poisoning case grips Chinese netizens worldwide". CNN. 14. ^ "The daily routine in Zhu Ling's family". China Daily. 15. ^ "Chinese Petition White House in Unsolved Poison Case". Bloomberg Businessweek. 16. ^ Andrew Jacobs (May 10, 2013). "Poison Attack Revives Fury in China Over '95 Case". The New York Times. Retrieved May 11, 2013. "It’s the lack of justice, the unfairness and the feeling that people with privilege can get away with anything," said Ms. He, an automotive engineer from China who now lives in Michigan. "People have just had enough." ## References[edit] * Bei Zhicheng, Cai Quanqing "For Help". Newsgroup: sci.med. 1994-04-10. Usenet: [email protected]. Retrieved 2012-06-12. SoS letter for Zhu Ling posted on Usenet April 10, 1994 * Yu Chih-Ho, Huang Ning China - Mystery Ailment Diagnosed Via Internet Newsbytes News Network, Sept 8, 1995 * Yu Renfei Zhu Ling's lawyers involved to collect evidences News Morning Post, March 14, 2006 * Jessie Tao Campus poisoning mystery triggers debate China Daily: English Version, January 13, 2006 * Wu Hongfei, et al. Ten-year unresolved poisoning case: the suspect is said to have special background Southern People Weekly, January 11, 2006 * Ash, Richard David; He, Min (2018). "Details of a thallium poisoning case revealed by single hair analysis using laser ablation inductively coupled plasma mass spectrometry". Forensic Science International. 292: 224–231. doi:10.1016/j.forsciint.2018.10.002. ISSN 0379-0738. PMID 30343235. * Jennifer Ouellette (25 December 2018). "Study brings us one step closer to solving 1994 thallium poisoning case". Ars Technica. Retrieved 26 December 2018. * "Mass spectrometry sheds new light on thallium poisoning cold case". sciencedaily.com. 2018-12-13. Retrieved 2018-12-25. ## External links[edit] * Help Zhu Ling Foundation * Youtube video: Who poisoned Zhu Ling? Documentation with English subtitle, made by huaren.us users, retrieved on April 27, 2013 * "Docs in China unable to diagnose this disease. HELP!!". Newsgroup: misc.education.medical. 1995-04-10. Usenet: [email protected]. Retrieved 2012-06-12. One of the original Usenet posts asking for help] * Sun Wei's first statement on Tianya Club (in Chinese, "孙维的声明－－驳斥朱令铊中毒案件引发的谣言"), December 30, 2005, retrieved on April 19, 2013 * Sun Wei's second statement on Tianya Club (in Chinese, "声明:要求重新侦查，为"窃听器"错误向网友和公安道歉"), January 13, 2006, retrieved on April 19, 2013 * The whole story about the Poisoning of Zhu Ling (in Chinese, "朱令被投毒事件始末", PDF file) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Thallium poisoning case of Zhu Ling	None	30,089	wikipedia	https://en.wikipedia.org/wiki/Thallium_poisoning_case_of_Zhu_Ling	2021-01-18T18:43:28	{"wikidata": ["Q8071124"]}
Familial hypercholanemia is a very rare genetic disorder characterized clinically by elevated serum bile acid concentrations, itching, and fat malabsorption reported in patients of Old Order Amish descent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Familial hypercholanemia	c1843139	30,090	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238475	2021-01-23T18:54:58	{"mesh": ["C564336"], "omim": ["607748"], "umls": ["C1843139"], "synonyms": ["Hereditary hypercholanemia"]}
A very rare hepatic and biliary tract tumor characterized by a growth pattern ressembling that found in hepatocellular carcinomas and cholangiocarcinomas but presenting atypical histological and immunohistochemical features (such as trabecular, organoid, microcystic and/or blastemal-like architecture and inhibin A, cytokeratin 7 and/or cytokeratin 19 positivity) that do not allow a formal diagnosis of the more common aforementioned liver cancers. Patients may present abdominal distension and pain, a palpable abdominal mass and elevated liver enzymes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Adenocarcinoma of the liver and intrahepatic biliary tract	None	30,091	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424943	2021-01-23T18:26:18	{"icd-10": ["C22.0"], "synonyms": ["Adenocarcinoma of the liver and IBT"]}
"Headless" redirects here. For other uses, see Headless (disambiguation). Acrania Partial absence of skull, bones, and scalp SpecialtyMedical genetics Acrania is a rare congenital disorder that occurs in the human fetus in which the flat bones in the cranial vault are either completely or partially absent.[1] The cerebral hemispheres develop completely but abnormally.[1] The condition is frequently, though not always, associated with anencephaly. The fetus is said to suffer from acrania if it meets the following criteria: the foetus should have a perfectly normal facial bone, a normal cervical column but without the fetal skull and a volume of brain tissue equivalent to at least one third of the normal brain size.[2] ## Contents * 1 Causes * 1.1 Genetics * 1.1.1 Genetic counseling * 1.2 Amniotic band syndrome * 2 Mechanism * 2.1 Ectodermal mesenchyme * 3 Diagnosis * 4 Prognosis * 5 References * 6 External links ## Causes[edit] Infant with both acrania and anencephaly. ### Genetics[edit] There are no known family ties in acrania and recurrence rates are extremely low. Not much is known about the exact mechanism involved in acrania. It is hypothesized that like other developmental malformations, there are multiple origins for acrania. Recent work has identified mutations in the hedgehog acyltransferase (HHAT) gene that have caused acrania along with holoprosencephaly and agnathia.[3] The mutation in HHAT which causes this disease is a loss-of-function mutation.[3] Before this discovery in 2010, HHAT was known to play a role in the sonic hedgehog pathway. When HHAT contains a loss-of-function mutation, less HHAT protein is produced. HHAT is necessary for the production of Hedgehog (Hh) proteins post-transcriptionally. As HHAT production decreases, production of long-range Hh proteins decreases proportionally. Decreases in Hh\| production disturb the production of extracellular signal-regulated kinases, bone morphogenetic proteins, and fibroblast growth factors, all of which play important roles in craniofacial patterning. Disruption of these pathways leads to abnormal bone and cartilage formation causing acrania and multiple other craniofacial patterning problems.[3] #### Genetic counseling[edit] Little genetic counseling can be offered for acrania because the genetic origins are not fully understood. In order to make genetic counseling for families easier this disease is often differentially diagnosed with other diseases that can occur at the same time such as anencephaly and acalvaria, though these diseases may not always occur simultaneously.[1] While this disease is tragic, reoccurrence rates are extremely low so genetic counseling is not always necessary.[1] ### Amniotic band syndrome[edit] During amniotic band syndrome (ABS), fibrous bands may entrap various parts of the developing fetus causing malformations. When these fibrous bands form around the developing skull, the bones will not form properly. ABS occurring in the developing brain neural tissue is one cause of acrania.[4] When ABS is the cause of acrania the fibrous bands cannot be detected through ultrasound.[4] ## Mechanism[edit] During the fourth week of human development the neuropore in a normally developing fetus closes. When this process is either interrupted or never initiated, acrania occurs.[2] The desmocranium becomes a membranous coverage instead of forming the epidermis of the scalp. Whether from being blocked by amniotic bands or by just not initiating, the migration of mesenchyme under the ectoderm does not occur.[2] Because this migration does not occur, the skull, and all involved muscles, are never formed.[2] Without the presence of the neurocranium, the brain fails to separate into two separate lobes. The hindbrain proceeds to develop normally, allowing for the child to be carried to term, but the diencephalon and ocular lobe remain small and underdeveloped.[2] ### Ectodermal mesenchyme[edit] Mesenchyme is formed in the developing embryo and will eventually become cartilage and bone. When ectodermal mesenchyme fails to migrate into the head region of the embryo, the skull will not be able to form. What exactly causes the failure of mesenchymal migration is unknown.[2] ## Diagnosis[edit] Acrania can be diagnosed early in pregnancy through an ultrasound. This abnormality appears during the beginning or end of the fourth week of the fetus's development. An absence of the skull is needed in order to make a diagnosis. A presence of brain tissue will confirm the diagnosis of acrania and differentiate it from other developmental problems such as anencephaly.[2] ## Prognosis[edit] Anencephaly is a fatal condition. Infants with anencephaly are stillborn in about 75 percent of cases. Newborns who survive die within several hours, days, or weeks.[5] This disease is rare, occurring in 1 in 20,000 live births.[6] In order to better manage an acrania diagnosis, early detection is of extreme importance.[2] Families may choose either to terminate the pregnancy, or to carry the child to term. Acrania may cause a fetus to spontaneously abort before reaching term.[2] ## References[edit] 1. ^ a b c d Bianca, Sebastiano; Ingegnosi, Carmela; Auditore, Salvatore; Reale, Armando; Galasso, M. G.; Bartoloni, Giovanni; Arancio, A.; Ettore, Giuseppe (2005). "Prenatal and postnatal findings of acrania". Archives of Gynecology and Obstetrics. 271 (3): 257–259. doi:10.1007/s00404-004-0621-2. ISSN 0932-0067. 2. ^ a b c d e f g h i Kwon, Tae Hee; King, Jim; Jeanty, Philippe (1991). "Acrania: Review of 13 Cases". The Fetus. ISSN 1057-137X. Archived from .net/page.php?id=77 the original Check `\|url=` value (help) on 2009-08-27. 3. ^ a b c Dennis, Jennifer F.; Kurosaka, Hiroshi; Iulianella, Angelo; Pace, Jennifer; Thomas, Nancy; Beckham, Sharon; Williams, Trevor; Trainor, Paul A. (2012). Beier, David R. (ed.). "Mutations in Hedgehog Acyltransferase (Hhat) Perturb Hedgehog Signaling, Resulting in Severe Acrania-Holoprosencephaly-Agnathia Craniofacial Defects". PLoS Genetics. 8 (10). e1002927. doi:10.1371/journal.pgen.1002927. ISSN 1553-7404. PMC 3464201. PMID 23055936. 4. ^ a b Cincore, Verdelia; Ninios, Anthanasios P.; Pavlik, Jacqueline; Hsu, Chaur-Dong (2003). "Prenatal Diagnosis of Acrania Associated with Amniotic Band Syndrome". Obstetrics & Gynecology. Elsevier. 102 (5 (part 2)): 1176–1178. doi:10.1016/S0029-7844(03)00118-2. ISSN 0029-7844. OCLC 110364612. PMID 14607048. 5. ^ https://my.clevelandclinic.org/health/diseases/15032-anencephaly 6. ^ Romero, Roberto; Pilu, Gianluigi; Jeanty, Philippe; Ghidini, Alessandro; Hobbins, John C. (1988). "Acrania" (PDF). Prenatal Diagnosis of Congenital Anomalies (PDF). East Norwalk, Connecticut: Appleton & Lange. pp. 75–76. ISBN 978-0-8385-7921-3. LCCN 87-14557. OCLC 571744822. OL 25881951M. Archived from the original (PDF) on 2012-09-11. Retrieved 2015-12-17. ## External links[edit] Classification D * ICD-10: Q00.0 * ICD-9-CM: 740.0 * SNOMED CT: 203923004 External resources * Orphanet: 945 * Acalvaria (Acrania) at NIH's Office of Rare Diseases * v * t * e Congenital malformations and deformations of nervous system Brain Neural tube defect * Anencephaly * Acephaly * Acrania * Acalvaria * Iniencephaly * Encephalocele * Chiari malformation Other * Microcephaly * Congenital hydrocephalus * Dandy–Walker syndrome * other reduction deformities * Holoprosencephaly * Lissencephaly * Microlissencephaly * Pachygyria * Hydranencephaly * Septo-optic dysplasia * Megalencephaly * Hemimegalencephaly * CNS cyst * Porencephaly * Schizencephaly * Polymicrogyria * Bilateral frontoparietal polymicrogyria Spinal cord Neural tube defect * Spina bifida * Rachischisis Other * Currarino syndrome * Diastomatomyelia * Syringomyelia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Acrania	c0702169	30,092	wikipedia	https://en.wikipedia.org/wiki/Acrania	2021-01-18T18:36:30	{"mesh": ["D009436"], "umls": ["C0702169"], "icd-9": ["740.0"], "icd-10": ["Q00.0"], "orphanet": ["945"], "wikidata": ["Q48686"]}
Idiopathic CD4+ lymphocytopenia Other namesImmunodeficiency 13 Idiopathic CD4+ lymphocytopenia is inherited via autosomal dominant manner[1] SpecialtyImmunology Idiopathic CD4+ lymphocytopenia (ICL) is a rare medical syndrome in which the body has too few CD4+ T lymphocytes, which are a kind of white blood cell.[2] ICL is sometimes characterized as "HIV-negative AIDS", though, in fact, its clinical presentation differs somewhat from that seen with HIV/AIDS.[3] People with ICL have a weakened immune system and are susceptible to opportunistic infections, although the rate of infections is lower than in people with AIDS.[4] ## Contents * 1 Cause * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Cause[edit] The cause of ICL, like all idiopathic conditions, is unknown. It does not appear to be caused by a transmissible agent, such as a virus.[5] It is widely believed that there is more than one cause.[6][non-primary source needed] ## Pathophysiology[edit] The loss of CD4+ T cells appears to be through apoptosis.[4][7] The accelerated deaths of the T cells is likely driven by crosslinking T cell receptors.[7] ## Diagnosis[edit] The mandatory criteria for diagnosis of idiopathic CD4+ lymphocytopenia include:[8] * Low numbers of CD4+ cells, on two or more measurements over at least six weeks: * CD4 cell count less than 300 cells per microliter, or * Less than 20% of T lymphocytes are CD4+ * Lack of laboratory evidence of HIV infection * Absence of any alternative explanation for the CD4 lymphocytopenia A one-time finding of low CD4+ cells is usually associated with a recent infection and resolves on its own.[7] Alternative explanations for the low CD4 counts include conditions such as blood cancers (aleukemia), treatment with chemotherapy, immunosuppressive medications, or other medications that suppress or kill T cells, infections, and problems with blood production.[2][9][non-primary source needed] All criteria must be fulfilled for a diagnosis of ICL. In addition, if these findings are present but combined with other significant findings, such as anemia or thrombocytopenia, then other diagnoses must be considered[citation needed]. ## Treatment[edit] Fludarabine-based hematopoietic stem cell transplantation (HSCT) has shown to be a feasible treatment for ICL.[10][non-primary source needed] ## Prognosis[edit] In contrast to the CD4+ cell depletion caused by HIV, in general, patients with idiopathic CD4 lymphocytopenia have a good prognosis.[6][11][12][13][non-primary source needed] The decline in CD4+ T-cells in patients with ICL is generally slower than that seen in HIV-infected patients.[3] The major risk to people with ICL is unexpected infections, including cryptococcus, atypical mycobacterial and Pneumocystis jiroveci pneumonia (PCP). The condition may also resolve on its own.[14] ICL sometimes precedes and may be the first signal of several blood cancers. ICL patients have developed primary effusion lymphoma,[15][non-primary source needed][16] primary leptomeningeal lymphoma,[9] diffuse large cell lymphoma,[17][non-primary source needed] MALT lymphoma,[18] and Burkitt's lymphoma,[19] among others. ICL may indirectly trigger autoimmune diseases. It has been associated with several cases of autoimmune disease Sjögren syndrome.[4][20] Because all of the reported autoimmune diseases and lymphomas involve B cells, one hypothesis proposes that ICL's narrow T cell repertoire predisposes the immune system to B cell disorders.[4] ## Epidemiology[edit] ICL is a very rare disease.[2] In 1993, a total of 47 confirmed cases were reported in a survey sponsored by the Centers for Disease Control.[21] ## References[edit] 1. ^ "OMIM Entry - # 615518 - IMMUNODEFICIENCY 13; IMD13". omim.org. Retrieved 21 July 2017. 2. ^ a b c Walker UA, Warnatz K (July 2006). "Idiopathic CD4 lymphocytopenia". Curr Opin Rheumatol. 18 (4): 389–95. doi:10.1097/01.bor.0000231908.57913.2f. PMID 16763460. S2CID 20289181. 3. ^ a b Luo L, Li T (December 2008). "Idiopathic CD4 lymphocytopenia and opportunistic infection--an update". FEMS Immunol. Med. Microbiol. 54 (3): 283–9. doi:10.1111/j.1574-695X.2008.00490.x. PMID 19049641. 4. ^ a b c d Wladis EJ, Kapila R, Chu DS (July 2005). "Idiopathic CD4+ lymphocytopenia and Sjogren syndrome" (PDF). Arch. Ophthalmol. 123 (7): 1012. doi:10.1001/archopht.123.7.1012-a. PMID 16009850. Archived from the original (PDF) on 2011-05-25. 5. ^ Online Medical Dictionary entry on T-lymphocytopenia Archived 2011-07-19 at the Wayback Machine 6. ^ a b Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM (February 1993). "Idiopathic CD4+ T-lymphocytopenia--four patients with opportunistic infections and no evidence of HIV infection". N. Engl. J. Med. 328 (6): 393–8. doi:10.1056/NEJM199302113280604. PMID 8093636. 7. ^ a b c Laurence J, Mitra D, Steiner M, Lynch DH, Siegal FP, Staiano-Coico L (February 1996). "Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia". J. Clin. Invest. 97 (3): 672–80. doi:10.1172/JCI118464. PMC 507103. PMID 8609222. 8. ^ UpToDate article on "Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients", by John G. Bartlett. Accessed 30 Oct 2006. 9. ^ a b Busse PJ, Cunningham-Rundles C (March 2002). "Primary leptomeningeal lymphoma in a patient with concomitant CD4+ lymphocytopenia". Ann. Allergy Asthma Immunol. 88 (3): 339–42. doi:10.1016/S1081-1206(10)62019-4. PMID 11926631. 10. ^ Hamidieh, A. A.; Pourpak, Z.; Hamdi, A.; Nabavi, M.; Ghavamzadeh, A. (2013). "Successful fludarabine-based hematopoietic stem cell transplantation in a pediatric patient with idiopathic CD4+ lymphocytopenia". Pediatric Transplantation. 17 (4): E109–11. doi:10.1111/petr.12086. PMID 23581828. 11. ^ Laurence J, Siegal F, Schattner E, Gelman I, Morse S (1992). "Acquired immunodeficiency without evidence of infection with human immunodeficiency virus types 1 and 2". Lancet. 340 (8814): 273–4. doi:10.1016/0140-6736(92)92359-N. PMID 1353194. S2CID 20114472. 12. ^ Ho D, Cao Y, Zhu T, Farthing C, Wang N, Gu G, Schooley R, Daar E (1993). "Idiopathic CD4+ T-lymphocytopenia--immunodeficiency without evidence of HIV infection". N Engl J Med. 328 (6): 380–5. doi:10.1056/NEJM199302113280602. PMID 8093634. 13. ^ Spira T, Jones B, Nicholson J, Lal R, Rowe T, Mawle A, Lauter C, Shulman J, Monson R (1993). "Idiopathic CD4+ T-lymphocytopenia--an analysis of five patients with unexplained opportunistic infections". N Engl J Med. 328 (6): 386–92. doi:10.1056/NEJM199302113280603. PMID 8093635. 14. ^ Zonios DI, Falloon J, Bennett JE, et al. (July 2008). "Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors". Blood. 112 (2): 287–294. doi:10.1182/blood-2007-12-127878. PMC 2442741. PMID 18456875. 15. ^ Niino D, Tsukasaki K, Torii K, et al. (January 2008). "Human herpes virus 8-negative primary effusion lymphoma with BCL6 rearrangement in a patient with idiopathic CD4 positive T-lymphocytopenia". Haematologica. 93 (1): e21–3. doi:10.3324/haematol.12085. PMID 18166773. 16. ^ Richetta A, Amoruso GF, Ascoli V, et al. (2007). "PEL, Kaposi's sarcoma HHV8+ and idiopathic T-lymphocitopenia CD4+". Clin Ter. 158 (2): 151–5. PMID 17566517. 17. ^ Campbell JK, Prince HM, Juneja SK, Seymour JF, Slavin M (April 2001). "Diffuse large cell lymphoma and t(8;22) (q24;q11) in a patient with idiopathic CD4+ T-lymphopenia". Leuk. Lymphoma. 41 (3–4): 421–3. doi:10.3109/10428190109057998. PMID 11378556. S2CID 23366810. 18. ^ Longo F, Hébuterne X, Michiels JF, Maniere A, Caroli-Bosc FX, Rampal P (January 1999). "[Multifocal MALT lymphoma and acute cytomegalovirus gastritis revealing CD4 lymphopenia without HIV infection]". Gastroenterol. Clin. Biol. (in French). 23 (1): 132–6. PMID 10219614. 19. ^ Shimano S, Murata N, Tsuchiya J (July 1997). "[Idiopathic CD4+ T-lymphocytopenia terminating in Burkitt's lymphoma]". Rinsho Ketsueki (in Japanese). 38 (7): 599–603. PMID 9267164. 20. ^ Mandl T, Bredberg A, Jacobsson LT, Manthorpe R, Henriksson G (April 2004). "CD4+ T-lymphocytopenia--a frequent finding in anti-SSA antibody seropositive patients with primary Sjögren's syndrome". J. Rheumatol. 31 (4): 726–8. PMID 15088298. 21. ^ Smith D, Neal J, Holmberg S (1993). "Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. An investigation of cases in the United States. The Centers for Disease Control Idiopathic CD4+ T-lymphocytopenia Task Force". N Engl J Med. 328 (6): 373–9. doi:10.1056/NEJM199302113280601. PMID 8093633. ## External links[edit] Classification D * ICD-10: D72.8 * OMIM: 615518 * MeSH: D018344 External resources * Orphanet: 228000 * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Idiopathic CD4+ lymphocytopenia	c0206744	30,093	wikipedia	https://en.wikipedia.org/wiki/Idiopathic_CD4%2B_lymphocytopenia	2021-01-18T18:35:04	{"gard": ["12375"], "mesh": ["D018344"], "umls": ["C0206744"], "icd-9": ["288.51"], "icd-10": ["D72.8"], "wikidata": ["Q1087632"]}
Failure of the heart to provide sufficient blood flow Heart failure Other namesChronic heart failure (CHF), congestive cardiac failure (CCF)[1][2][3] A man with congestive heart failure and marked jugular venous distension. External jugular vein marked by an arrow. SpecialtyCardiology SymptomsShortness of breath, feeling tired, leg swelling[4] DurationUsually lifelong CausesHeart attack, high blood pressure, abnormal heart rhythm, excessive alcohol use, infection, heart damage[4][5] Risk factorsSmoking, sedentary lifestyle Diagnostic methodEchocardiogram[6] Differential diagnosisKidney failure, thyroid disease, liver disease, anemia, obesity[7] MedicationDiuretics, cardiac medications[6][8] Frequency40 million (2015),[9] 1–2% of adults (developed countries)[5][10] Deaths35% risk of death in first year[4] Heart failure (HF), also known as congestive heart failure (CHF), decompensatio cordis (DC), and congestive cardiac failure (CCF), is when the heart is unable to pump sufficiently to maintain blood flow to meet the body tissue's needs for metabolism.[11][12][13][14] Signs and symptoms of heart failure commonly include shortness of breath, excessive tiredness, and leg swelling.[4] The shortness of breath is usually worse with exercise or while lying down, and may wake the person at night.[4] A limited ability to exercise is also a common feature.[15] Chest pain, including angina, does not typically occur due to heart failure.[16] Common causes of heart failure include coronary artery disease, including a previous myocardial infarction (heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of an unknown cause.[4][5] These cause heart failure by changing either the structure or the function of the heart.[4] The two types of left ventricular heart failure – heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) – are based on whether the ability of the left ventricle to contract, or to relax, is affected.[4] The severity of the heart failure is graded by the severity of symptoms with exercise.[7] Heart failure is not the same as heart attack (in which part of the heart muscle dies) or cardiac arrest (in which blood flow stops altogether).[17][18] Other diseases that may have symptoms similar to heart failure include obesity, kidney failure, liver problems, anemia, and thyroid disease.[7] Diagnosis is based on symptoms, physical findings, and echocardiography.[6] Blood tests, electrocardiography, and chest radiography may be useful to determine the underlying cause.[6] Treatment depends on the severity and cause of the disease.[6] In people with chronic stable mild heart failure, treatment commonly consists of lifestyle modifications such as stopping smoking, physical exercise, and dietary changes, as well as medications.[8][19] In those with heart failure due to left ventricular dysfunction, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or valsartan/sacubitril along with beta blockers are recommended.[6][20] For those with severe disease, aldosterone antagonists, or hydralazine with a nitrate may be used.[6] Diuretics are useful for preventing fluid retention and the resulting shortness of breath.[8] Sometimes, depending on the cause, an implanted device such as a pacemaker or an implantable cardiac defibrillator may be recommended.[6] In some moderate or severe cases, cardiac resynchronization therapy (CRT)[21] or cardiac contractility modulation may be of benefit.[22] A ventricular assist device (for the left, right, or both ventricles), or occasionally a heart transplant may be recommended in those with severe disease that persists despite all other measures.[8] Heart failure is a common, costly, and potentially fatal condition.[23] In 2015, it affected about 40 million people globally.[9] Overall around 2% of adults have heart failure[23] and in those over the age of 65, this increases to 6–10%.[5][24] Rates are predicted to increase.[23] The risk of death is about 35% the first year after diagnosis, while by the second year the risk of death is less than 10% for those who remain alive.[4] This degree of risk of death is similar to some cancers.[4] In the United Kingdom, the disease is the reason for 5% of emergency hospital admissions.[4] Heart failure has been known since ancient times, with the Ebers papyrus commenting on it around 1550 BCE.[15] ## Contents * 1 Signs and symptoms * 1.1 Left-sided failure * 1.2 Right-sided failure * 1.3 Biventricular failure * 2 Causes * 2.1 High-output heart failure * 2.2 Acute decompensation * 2.3 Medications * 2.4 Supplements * 3 Pathophysiology * 4 Diagnosis * 4.1 Classification * 4.2 Ultrasound * 4.3 Chest X-ray * 4.4 Electrophysiology * 4.5 Blood tests * 4.6 Angiography * 4.7 Algorithms * 4.7.1 Framingham criteria * 4.7.2 ESC algorithm * 4.8 Staging * 4.9 Histopathology * 5 Prevention * 6 Management * 6.1 Acute decompensation * 6.2 Chronic management * 6.2.1 Monitoring * 6.2.2 Lifestyle * 6.2.3 Medication * 6.2.4 Implanted devices * 6.2.5 Surgical therapies * 6.3 Palliative care * 7 Prognosis * 8 Epidemiology * 8.1 United States * 8.2 United Kingdom * 8.3 Developing world * 8.4 Sex * 8.5 Ethnicity * 9 Economics * 10 Research directions * 11 References * 12 External links ## Signs and symptoms[edit] Signs and symptoms of severe heart failure.[25] Heart failure is a pathophysiological state in which cardiac output is insufficient to meet the needs of the body and lungs.[4] The term "congestive heart failure" is often used, as one of the common symptoms is congestion, or build-up of fluid in a person's tissues and veins in the lungs or other parts of the body.[4] Specifically, congestion takes the form of water retention and swelling (edema), both as peripheral edema (causing swollen limbs and feet) and as pulmonary edema (causing breathing difficulty), as well as ascites (swollen abdomen). Heart failure symptoms are traditionally and somewhat arbitrarily divided into left- and right-sided, recognizing that the left and right ventricles of the heart supply different portions of the circulation, but people commonly have both sets of signs and symptoms. ### Left-sided failure[edit] The left side of the heart receives oxygen-rich blood from the lungs and pumps it forward to the systemic circulation (the rest of the body except for the pulmonary circulation). Failure of the left side of the heart causes blood to back up (be congested) into the lungs, causing respiratory symptoms and fatigue due to insufficient supply of oxygenated blood. Common respiratory signs are increased rate of breathing and increased work of breathing (nonspecific signs of respiratory distress). Rales or crackles, heard initially in the lung bases, and when severe, throughout the lung fields suggest the development of pulmonary edema (fluid in the alveoli). Cyanosis, which suggests severe low blood oxygen, is a late sign of extremely severe pulmonary edema. Additional signs indicating left ventricular failure include a laterally displaced apex beat (which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds) may be heard as a marker of increased blood flow or increased intracardiac pressure. Heart murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure. Backward failure of the left ventricle causes congestion of the lungs' blood vessels, so the symptoms are predominantly respiratory in nature. Backward failure can be subdivided into the failure of the left atrium, the left ventricle, or both within the left circuit. The person will have dyspnea (shortness of breath) on exertion and in severe cases, dyspnea at rest. Increasing breathlessness on lying flat, called orthopnea, occurs. It is often measured in the number of pillows required to lie comfortably, and in orthopnea, the person may resort to sleeping while sitting up. Another symptom of heart failure is paroxysmal nocturnal dyspnea: a sudden night-time attack of severe breathlessness, usually several hours after going to sleep. Easy fatigability and exercise intolerance are also common complaints related to respiratory compromise. "Cardiac asthma" or wheezing may occur. Compromise of left ventricular forward function may result in symptoms of poor systemic circulation such as dizziness, confusion, and cool extremities at rest. ### Right-sided failure[edit] Severe peripheral (pitting) edema Right-sided heart failure is often caused by pulmonary heart disease (cor pulmonale), which is typically caused by difficulties of the pulmonary circulation, such as pulmonary hypertension or pulmonic stenosis. Physical examination may reveal pitting peripheral edema, ascites, liver enlargement, and spleen enlargement. Jugular venous pressure is frequently assessed as a marker of fluid status, which can be accentuated by eliciting hepatojugular reflux. If the right ventricular pressure is increased, a parasternal heave may be present, signifying the compensatory increase in contraction strength. Backward failure of the right ventricle leads to congestion of systemic capillaries. This generates excess fluid accumulation in the body. This causes swelling under the skin (termed peripheral edema or anasarca) and usually affects the dependent parts of the body first (causing foot and ankle swelling in people who are standing up, and sacral edema in people who are predominantly lying down). Nocturia (frequent night-time urination) may occur when fluid from the legs is returned to the bloodstream while lying down at night. In progressively severe cases, ascites (fluid accumulation in the abdominal cavity causing swelling) and liver enlargement may develop. Significant liver congestion may result in impaired liver function (congestive hepatopathy), and jaundice and even coagulopathy (problems of decreased or increased blood clotting) may occur. ### Biventricular failure[edit] Dullness of the lung fields to finger percussion and reduced breath sounds at the bases of the lung may suggest the development of a pleural effusion (fluid collection between the lung and the chest wall). Though it can occur in isolated left- or right-sided heart failure, it is more common in biventricular failure because pleural veins drain into both the systemic and pulmonary venous systems. When unilateral, effusions are often right-sided. If a person with a failure of one ventricle lives long enough, it will tend to progress to failure of both ventricles. For example, left ventricular failure allows pulmonary edema and pulmonary hypertension to occur, which increase stress on the right ventricle. Right ventricular failure is not as deleterious to the other side, but neither is it harmless. ## Causes[edit] Heart failure can be caused by a large number of cardiac diseases. In addition to the causes mentioned above, viral infections of the heart can lead to inflammation of the muscular layer of the heart and subsequently contribute to the development of heart failure. Genetic predisposition plays an important role. If more than one cause is present, progression is more likely and prognosis is worse.[26] Heart damage can predispose a person to develop heart failure later in life and has many causes including systemic viral infections (e.g., HIV), chemotherapeutic agents such as daunorubicin, cyclophosphamide, trastuzumab and abuse of drugs such as alcohol, cocaine, and methamphetamine. An uncommon cause is exposure to certain toxins such as lead and cobalt. Additionally, infiltrative disorders such as amyloidosis and connective tissue diseases such as systemic lupus erythematosus have similar consequences. Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps with obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart failure.[27] Recent reports from clinical trials have also linked variation in blood pressure to heart failure[28][29] and cardiac changes that may give rise to heart failure.[30] ### High-output heart failure[edit] Heart failure may also occur in situations of "high output" (termed "high-output heart failure"), where the amount of blood pumped is more than typical and the heart is unable to keep up.[31] This can occur in overload situations (e.g., blood or serum infusions), kidney diseases, chronic severe anemia, beriberi (vitamin B1/thiamine deficiency), hyperthyroidism, cirrhosis, Paget's disease, multiple myeloma, arteriovenous fistulae, or arteriovenous malformations. ### Acute decompensation[edit] Main article: Acute decompensated heart failure Kerley B lines in acute cardiac decompensation. The short, horizontal lines can be found everywhere in the right lung. Chronic stable heart failure may easily decompensate. This most commonly results from a concurrent illness (such as myocardial infarction (a heart attack) or pneumonia), abnormal heart rhythms, uncontrolled hypertension, or a person's failure to maintain a fluid restriction, diet, or medication.[32] Other factors that may worsen CHF include: anemia, hyperthyroidism, excessive fluid or salt intake, and medication such as NSAIDs and thiazolidinediones.[33] NSAIDs increase the risk twofold.[34] ### Medications[edit] A number of medications may cause or worsen the disease. This includes NSAIDS, COX-2 inhibitors, a number of anesthetic agents such as ketamine, thiazolidinediones, some cancer medications, several antiarrhythmic medications, pregabalin, alpha-2 adrenergic receptor agonists, minoxidil, itraconazole, cilostazol, anagrelide, stimulants (e.g., methylphenidate), tricyclic antidepressants, lithium, antipsychotics, dopamine agonists, TNF inhibitors, calcium channel blockers, salbutamol, and tamsulosin.[35] By inhibiting the formation of prostaglandins, NSAIDs may exacerbate heart failure through several mechanisms, including promotion of fluid retention, increasing blood pressure, and decreasing a person's response to diuretic medications.[35] Similarly, the ACC/AHA recommends against the use of COX-2 inhibitor medications in people with heart failure.[35] Thiazolidinediones have been strongly linked to new cases of heart failure and worsening of pre-existing congestive heart failure due to their association with weight gain and fluid retention.[35] Certain calcium channel blockers, such as diltiazem and verapamil, are known to decrease the force with which the heart ejects blood, thus are not recommended in people with heart failure with a reduced ejection fraction.[35] ### Supplements[edit] Certain alternative medicines carry a risk of exacerbating existing heart failure, and are not recommended.[35] This includes aconite, ginseng, gossypol, gynura, licorice, lily of the valley, tetrandrine, and yohimbine.[35] Aconite can cause abnormally slow heart rates and abnormal heart rhythms such as ventricular tachycardia.[35] Ginseng can cause abnormally low or high blood pressure, and may interfere with the effects of diuretic medications.[35] Gossypol can increase the effects of diuretics, leading to toxicity.[35] Gynura can cause low blood pressure.[35] Licorice can worsen heart failure by increasing blood pressure and promoting fluid retention.[35] Lily of the valley can cause abnormally slow heart rates with mechanisms similar to those of digoxin.[35] Tetrandrine can lead to low blood pressure through inhibition of L-type calcium channels.[35] Yohimbine can exacerbate heart failure by increasing blood pressure through alpha-2 adrenergic receptor antagonism.[35] ## Pathophysiology[edit] Main article: Pathophysiology of heart failure Model of a normal heart, with contracted muscle (left); and a weakened heart, with over-stretched muscle (right) Heart failure is caused by any condition that reduces the efficiency of the heart muscle, through damage or overloading. Over time, these increases in workload, which are mediated by long-term activation of neurohormonal systems such as the renin–angiotensin system, lead to fibrosis, dilation, and structural changes in the shape of the left ventricle from elliptical to spherical.[23] The heart of a person with heart failure may have a reduced force of contraction due to overloading of the ventricle. In a normal heart, increased filling of the ventricle results in increased contraction force by the Frank–Starling law of the heart, and thus a rise in cardiac output. In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link actin and myosin filaments in over-stretched heart muscle.[36] ## Diagnosis[edit] No diagnostic criteria have been agreed on as the gold standard for heart failure. The National Institute for Health and Care Excellence recommends measuring brain natriuretic peptide (BNP) followed by an ultrasound of the heart if positive.[37] This is recommended in those with shortness of breath.[38] In those with worsening heart failure, both a BNP and a troponin are recommended to help determine likely outcomes.[38] ### Classification[edit] One historical method of categorizing heart failure is by the side of the heart involved (left heart failure versus right heart failure). Right heart failure was thought to compromise blood flow to the lungs compared to left heart failure compromising blood flow to the aorta and consequently to the brain and the remainder of the body's systemic circulation. However, mixed presentations are common and left heart failure is a common cause of right heart failure.[39] More accurate classification of heart failure type is made by measuring ejection fraction, or the proportion of blood pumped out of the heart during a single contraction.[40] Ejection fraction is given as a percentage with the normal range being between 50 and 75%.[40] The two types are: 1) Heart failure due to reduced ejection fraction (HFrEF): Synonyms no longer recommended are "heart failure due to left ventricular systolic dysfunction" and "systolic heart failure". HFrEF is associated with an ejection fraction less than 40%.[41] 2) Heart failure with preserved ejection fraction (HFpEF): Synonyms no longer recommended include "diastolic heart failure" and "heart failure with normal ejection fraction."[4][19] HFpEF occurs when the left ventricle contracts normally during systole, but the ventricle is stiff and does not relax normally during diastole, which impairs filling.[4] Heart failure may also be classified as acute or chronic. Chronic heart failure is a long-term condition, usually kept stable by the treatment of symptoms. Acute decompensated heart failure is a worsening of chronic heart failure symptoms, which can result in acute respiratory distress.[42] High-output heart failure can occur when there is increased cardiac demand that results in increased left ventricular diastolic pressure which can develop into pulmonary congestion (pulmonary edema).[31] Several terms are closely related to heart failure and may be the cause of heart failure, but should not be confused with it. Cardiac arrest and asystole refer to situations in which no cardiac output occurs at all. Without urgent treatment, these result in sudden death. Myocardial infarction ("Heart attack") refers to heart muscle damage due to insufficient blood supply, usually as a result of a blocked coronary artery. Cardiomyopathy refers specifically to problems within the heart muscle, and these problems can result in heart failure. Ischemic cardiomyopathy implies that the cause of muscle damage is coronary artery disease. Dilated cardiomyopathy implies that the muscle damage has resulted in enlargement of the heart. Hypertrophic cardiomyopathy involves enlargement and thickening of the heart muscle. ### Ultrasound[edit] Echocardiography is commonly used to support a clinical diagnosis of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV in proportion to the EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred measure of systolic function. Normally, the EF should be between 50 and 70%; in systolic heart failure, it drops below 40%. Echocardiography can also identify valvular heart disease and assess the state of the pericardium (the connective tissue sac surrounding the heart). Echocardiography may also aid in deciding what treatments will help the person, such as medication, insertion of an implantable cardioverter-defibrillator, or cardiac resynchronization therapy. Echocardiography can also help determine if acute myocardial ischemia is the precipitating cause, and may manifest as regional wall motion abnormalities on echo. * Play media Ultrasound showing severe systolic heart failure[43] * Play media Ultrasound showing severe systolic heart failure[43] * Play media Ultrasound of the lungs showing edema due to severe systolic heart failure[43] * Play media Ultrasound showing severe systolic heart failure[43] * Ultrasound showing severe systolic heart failure[43] ### Chest X-ray[edit] Chest radiograph of a lung with distinct Kerley B lines, as well as an enlarged heart (as shown by an increased cardiothoracic ratio, cephalization of pulmonary veins, and minor pleural effusion as seen for example in the right horizontal fissure. Yet, no obvious lung edema is seen. Overall, this indicates intermediate severity (stage II) heart failure. Chest X-rays are frequently used to aid in the diagnosis of CHF. In a person who is compensated, this may show cardiomegaly (visible enlargement of the heart), quantified as the cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure, evidence may exist of vascular redistribution (upper lobe blood diversion or cephalization), Kerley lines, cuffing of the areas around the bronchi, and interstitial edema. Ultrasound of the lung may also be able to detect Kerley lines.[44] * Congestive heart failure with small bilateral effusions * Kerley B lines ### Electrophysiology[edit] An electrocardiogram (ECG/EKG) may be used to identify arrhythmias, ischemic heart disease, right and left ventricular hypertrophy, and presence of conduction delay or abnormalities (e.g. left bundle branch block). Although these findings are not specific to the diagnosis of heart failure, a normal ECG virtually excludes left ventricular systolic dysfunction.[45] ### Blood tests[edit] Blood tests routinely performed include electrolytes (sodium, potassium), measures of kidney function, liver function tests, thyroid function tests, a complete blood count, and often C-reactive protein if infection is suspected. An elevated brain natriuretic peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP can be used to differentiate between causes of dyspnea due to heart failure from other causes of dyspnea. If myocardial infarction is suspected, various cardiac markers may be used. BNP is a better indicator than N-terminal pro-BNP for the diagnosis of symptomatic heart failure and left ventricular systolic dysfunction. In symptomatic people, BNP had a sensitivity of 85% and specificity of 84% in detecting heart failure; performance declined with increasing age.[46] Hyponatremia (low serum sodium concentration) is common in heart failure. Vasopressin levels are usually increased, along with renin, angiotensin II, and catecholamines to compensate for reduced circulating volume due to inadequate cardiac output. This leads to increased fluid and sodium retention in the body; the rate of fluid retention is higher than the rate of sodium retention in the body, this phenomenon causes hypervolemic hyponatremia (low sodium concentration due to high body fluid retention). This phenomenon is more common in older women with low body mass. Severe hyponatremia can result in accumulation of fluid in the brain, causing cerebral edema and intracranial hemorrhage.[47] ### Angiography[edit] Angiography is the X-ray imaging of blood vessels, which is done by injecting contrast agents into the bloodstream through a thin plastic tube (catheter), which is placed directly in the blood vessel. X-ray images are called angiograms.[48] Heart failure may be the result of coronary artery disease, and its prognosis depends in part on the ability of the coronary arteries to supply blood to the myocardium (heart muscle). As a result, coronary catheterization may be used to identify possibilities for revascularisation through percutaneous coronary intervention or bypass surgery. ### Algorithms[edit] Various algorithms are used for the diagnosis of heart failure. For example, the algorithm used by the Framingham Heart Study adds together criteria mainly from physical examination. In contrast, the more extensive algorithm by the European Society of Cardiology weights the difference between supporting and opposing parameters from the medical history, physical examination, further medical tests, and response to therapy. #### Framingham criteria[edit] By the Framingham criteria, diagnosis of congestive heart failure (heart failure with impaired pumping capability)[49] requires the simultaneous presence of at least two of the following major criteria or one major criterion in conjunction with two of the minor criteria. Major criteria include an enlarged heart on a chest X-ray, an S3 gallop (a third heart sound), acute pulmonary edema, episodes of waking up from sleep gasping for air, crackles on lung auscultation, central venous pressure more than 16 cm H 2O at the right atrium, jugular vein distension, positive abdominojugular test, and weight loss more than 4.5 kg in 5 days in response to treatment (sometimes[50] classified as a minor criterion).[51] Minor criteria include an abnormally fast heart rate more than 120 beats per minute, nocturnal cough, difficulty breathing with physical activity, pleural effusion, a decrease in the vital capacity by one-third from maximum recorded, liver enlargement, and bilateral ankle edema.[51] Minor criteria are acceptable only if they can not be attributed to another medical condition such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome.[51] The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure.[51] #### ESC algorithm[edit] The ESC algorithm weights these parameters in establishing the diagnosis of heart failure:[24] Diagnostic assessments supporting the presence of heart failure Assessment Diagnosis of heart failure Supports if present Opposes if normal or absent Compatible symptoms ++ ++ Compatible signs ++ \+ Cardiac dysfunction on echocardiography +++ +++ Response of symptoms or signs to therapy +++ ++ ECG Normal ++ Abnormal ++ \+ Dysrhythmia +++ \+ Laboratory Elevated BNP/NT-proBNP +++ \+ Low/normal BNP/NT-proBNP + +++ Low blood sodium + \+ Kidney dysfunction + \+ Mild elevations of troponin + \+ Chest X-ray Pulmonary congestion +++ \+ Reduced exercise capacity +++ ++ Abnormal pulmonary function tests + \+ Abnormal hemodynamics at rest +++ ++ \+ = some importance; ++ = intermediate importance; +++ = great importance. ### Staging[edit] Heart failure is commonly stratified by the degree of functional impairment conferred by the severity of the heart failure (as reflected in the New York Heart Association (NYHA) Functional Classification.[52]) The NYHA functional classes (I-IV) begin with class I, which is defined as a person who experiences no limitation in any activities and has no symptoms from ordinary activities. People with NYHA class II heart failure have slight, mild limitation with everyday activities; the person is comfortable at rest or with mild exertion. With NYHA class III heart failure, a marked limitation occurs with any activity; the person is comfortable only at rest. A person with NYHA class IV heart failure is symptomatic at rest and becomes quite uncomfortable with any physical activity. This score documents the severity of symptoms and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and does not reliably predict the walking distance or exercise tolerance on formal testing.[53] In its 2001 guidelines, the American College of Cardiology/American Heart Association working group introduced four stages of heart failure:[54] * Stage A: People at high risk for developing HF in the future, but no functional or structural heart disorder * Stage B: A structural heart disorder, but no symptoms at any stage * Stage C: Previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment * Stage D: Advanced disease requiring hospital-based support, a heart transplant, or palliative care The ACC staging system is useful since stage A encompasses "pre-heart failure" – a stage where intervention with treatment can presumably prevent progression to overt symptoms. ACC stage A does not have a corresponding NYHA class. ACC stage B would correspond to NYHA class I. ACC stage C corresponds to NYHA class II and III, while ACC stage D overlaps with NYHA class IV. * The degree of coexisting illness: i.e. heart failure/systemic hypertension, heart failure/pulmonary hypertension, heart failure/diabetes, heart failure/kidney failure, etc. * Whether the problem is primarily increased venous back pressure (preload), or failure to supply adequate arterial perfusion (afterload) * Whether the abnormality is due to low cardiac output with high systemic vascular resistance or high cardiac output with low vascular resistance (low-output heart failure vs. high-output heart failure) ### Histopathology[edit] Siderophages (one indicated by white arrow) and pulmonary congestion, indicating left congestive heart failure Histopathology can diagnose heart failure in autopsies. The presence of siderophages indicates chronic left-sided heart failure, but is not specific for it.[55] It is also indicated by congestion of the pulmonary circulation. ## Prevention[edit] A person's risk of developing heart failure is inversely related to level of physical activity. Those who achieved at least 500 MET-minutes/week (the recommended minimum by U.S. guidelines) had lower heart failure risk than individuals who did not report exercising during their free time; the reduction in heart failure risk was even greater in those who engaged in higher levels of physical activity than the recommended minimum.[56] Heart failure can also be prevented by lowering high blood pressure and high blood cholesterol, and by controlling diabetes. Maintaining a healthy weight, and decreasing sodium, alcohol, and sugar intake, may help. Additionally, avoiding tobacco use has been shown to lower the risk of heart failure.[57] ## Management[edit] Main article: Management of heart failure Treatment focuses on improving the symptoms and preventing the progression of the disease. Reversible causes of the heart failure also need to be addressed (e.g. infection, alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, and hypertension). Treatments include lifestyle and pharmacological modalities, occasionally various forms of device therapy, and rarely cardiac transplantation. ### Acute decompensation[edit] Main article: Acute decompensated heart failure In acute decompensated heart failure, the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing, and circulation are adequate. Immediate treatments usually involve some combination of vasodilators such as nitroglycerin, diuretics such as furosemide, and possibly noninvasive positive pressure ventilation. Supplemental oxygen is indicated in those with oxygen saturation levels below 90%, but is not recommended in those with normal oxygen levels in normal atmosphere.[58] ### Chronic management[edit] The goals of treatment for people with chronic heart failure are the prolongation of life, prevention of acute decompensation, and reduction of symptoms, allowing for greater activity. Heart failure can result from a variety of conditions. In considering therapeutic options, excluding reversible causes is of primary importance, including thyroid disease, anemia, chronic tachycardia, alcohol abuse, hypertension, and dysfunction of one or more heart valves. Treatment of the underlying cause is usually the first approach to treating heart failure. In the majority of cases, though, either no primary cause is found or treatment of the primary cause does not restore normal heart function. In these cases, behavioral, medical and device treatment strategies exist that can provide a significant improvement in outcomes, including the relief of symptoms, exercise tolerance, and a decrease in the likelihood of hospitalization or death. Breathlessness rehabilitation for chronic obstructive pulmonary disease and heart failure has been proposed with exercise training as a core component. Rehabilitation should also include other interventions to address shortness of breath including psychological and education needs of people and needs of carers.[59] Iron supplementation appears useful in those with iron deficiency anemia and heart failure.[60] #### Monitoring[edit] The various measures often used to assess the progress of people being treated for heart failure include fluid balance (calculation of fluid intake and excretion) and monitoring body weight (which in the shorter term reflects fluid shifts).[61] Remote monitoring can be effective to reduce complications for people with heart failure.[62][63] #### Lifestyle[edit] Behavior modification is a primary consideration in chronic heart failure management program, with dietary guidelines regarding fluid and salt intake.[64] Fluid restriction is important to reduce fluid retention in the body and to correct the hyponatremic status of the body.[47] The evidence of benefit of reducing salt, however, is poor as of 2018.[65] Exercise should be encouraged and tailored to suit individual capabilities. The inclusion of regular physical conditioning as part of a cardiac rehabilitation program can significantly improve quality of life and reduce the risk of hospital admission for worsening symptoms, but no evidence shows a reduction in mortality rates as a result of exercise. Furthermore, whether this evidence can be extended to people with HFpEF or to those whose exercise regimen takes place entirely at home is unclear.[19] Home visits and regular monitoring at heart-failure clinics reduce the need for hospitalization and improve life expectancy.[66] #### Medication[edit] First-line therapy for people with heart failure due to reduced systolic function should include angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) if the person develops a long-term cough as a side effect of the ACE-I.[67] Use of medicines from this class is associated with improved survival, fewer hospitalizations for heart failure exacerbations, and improved quality of life in people with heart failure.[68] Beta-adrenergic blocking agents (beta blockers) also form part of the first line of treatment, adding to the improvement in symptoms and mortality provided by ACE-I/ARB.[68][69] The mortality benefits of beta blockers in people with systolic dysfunction who also have atrial fibrillation is more limited than in those who do not have it.[70] If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed, but reduction in hospital admission for uncontrolled symptoms has not been observed.[71] In people who are intolerant of ACE-I and ARBs or who have significant kidney dysfunction, the use of combined hydralazine and a long-acting nitrate, such as isosorbide dinitrate, is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure.[72] It is especially beneficial in African-Americans (AA).[72] In AAs who are symptomatic, hydralazine and isosorbide dinitrate (H+I) can be added to ACE-I or ARBs. In people with symptomatic heart failure with markedly reduced ejection fraction (anyone with an ejection fraction of 35% or lower or less than 40% if following a heart attack), the use of an mineralocorticoid antagonist, such as spironolactone or eplerenone, in addition to beta blockers and ACE-I (once titrated to the target dose or maximum tolerated dose), can improve symptoms and reduce mortality.[73][74] Sacubitril/valsartan should be used in those who still have symptoms while on an ACE-I or ARB, beta blocker, and a mineralocorticoid receptor antagonist as it reduces the risks of cardiovascular mortality and hospitalisation for heart failure by a further 4.7% (absolute risk reduction). However, the use of this combination agent requires the cessation of ACE-i or ARB therapy 48 hours before its initiation.[75] Second-line medications for CHF do not confer a mortality benefit. Digoxin is one such medication. Its narrow therapeutic window, a high degree of toxicity, and the failure of multiple trials to show a mortality benefit have reduced its role in clinical practice. It is now used in only a small number of people with refractory symptoms, who are in atrial fibrillation, and/or who have chronic hypotension.[citation needed] Diuretics have been a mainstay of treatment for treatment of fluid accumulation, and include diuretics classes such as loop diuretics, thiazide-like diuretics, and potassium-sparing diuretics. Although widely used, evidence on their efficacy and safety is limited, with the exception of mineralocorticoid antagonists such as spironolactone.[73][76] Mineralocorticoid antagonists in those under 75 years old appear to decrease the risk of death.[77] A recent Cochrane review found that in small studies, the use of diuretics appeared to have improved mortality in individuals with heart failure.[78] However, the extent to which these results can be extrapolated to a general population is unclear due to the small number of participants in the cited studies.[76] Anemia is an independent factor in mortality in people with chronic heart failure. Treatment of anemia significantly improves quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates.[79][80] The European Society of Cardiology guideline in 2016 recommend screening for iron-deficiency anemia and treating with intravenous iron if deficiency is found.[10] The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions which increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative.[81] Vasopressin receptor antagonists can also be used to treat heart failure. Conivaptan is the first medication approved by US Food and Drug Administration for the treatment of euvolemic hyponatremia in those with heart failure.[47] In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia.[47] Ivabradine is recommended for people with symptomatic heart failure with reduced left ventricular ejection fraction who are receiving optimized guideline directed therapy (as above) including the maximum tolerated dose of beta blocker, have a normal heart rhythm, and continue to have a resting heart rate above 70 beats per minute.[38] Ivabradine has been found to reduce the risk of hospitalization for heart failure exacerbations in this subgroup of people with heart failure.[38] #### Implanted devices[edit] In people with severe cardiomyopathy (left ventricular ejection fraction below 35%), or in those with recurrent VT or malignant arrhythmias, treatment with an automatic implantable cardioverter-defibrillator (AICD) is indicated to reduce the risk of severe life-threatening arrhythmias. The AICD does not improve symptoms or reduce the incidence of malignant arrhythmias, but does reduce mortality from those arrhythmias, often in conjunction with antiarrhythmic medications. In people with left ventricular ejection (LVEF) below 35%, the incidence of ventricular tachycardia or sudden cardiac death is high enough to warrant AICD placement. Its use is therefore recommended in AHA/ACC guidelines.[21] Cardiac contractility modulation (CCM) is a treatment for people with moderate to severe left ventricular systolic heart failure (NYHA class II–IV), which enhances both the strength of ventricular contraction and the heart's pumping capacity. The CCM mechanism is based on stimulation of the cardiac muscle by nonexcitatory electrical signals, which are delivered by a pacemaker-like device. CCM is particularly suitable for the treatment of heart failure with normal QRS complex duration (120 ms or less) and has been demonstrated to improve the symptoms, quality of life, and exercise tolerance.[22][82][83][84][85] CCM is approved for use in Europe, but not currently in North America.[86][87] About one-third of people with LVEF below 35% have markedly altered conduction to the ventricles, resulting in dyssynchronous depolarization of the right and left ventricles. This is especially problematic in people with left bundle branch block (blockage of one of the two primary conducting fiber bundles that originate at the base of the heart and carry depolarizing impulses to the left ventricle). Using a special pacing algorithm, biventricular cardiac resynchronization therapy (CRT) can initiate a normal sequence of ventricular depolarization. In people with LVEF below 35% and prolonged QRS duration on ECG (LBBB or QRS of 150 ms or more), an improvement in symptoms and mortality occurs when CRT is added to standard medical therapy.[88] However, in the two-thirds of people without prolonged QRS duration, CRT may actually be harmful.[21][22][89] #### Surgical therapies[edit] People with the most severe heart failure may be candidates for ventricular assist devices, which have commonly been used as a bridge to heart transplantation, but have been used more recently as a destination treatment for advanced heart failure.[90] In select cases, heart transplantation can be considered. While this may resolve the problems associated with heart failure, the person must generally remain on an immunosuppressive regimen to prevent rejection, which has its own significant downsides.[91] A major limitation of this treatment option is the scarcity of hearts available for transplantation. ### Palliative care[edit] People with heart failure often have significant symptoms, such as shortness of breath and chest pain. Palliative care should be initiated early in the HF trajectory, and should not be an option of last resort.[92] Palliative care can not only provide symptom management, but also assist with advanced care planning, goals of care in the case of a significant decline, and making sure the person has a medical power of attorney and discussed his or her wishes with this individual.[93] A 2016 and 2017 review found that palliative care is associated with improved outcomes, such as quality of life, symptom burden, and satisfaction with care.[92][94] Without transplantation, heart failure may not be reversible and heart function typically deteriorates with time. The growing number of people with stage IV heart failure (intractable symptoms of fatigue, shortness of breath, or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice, according to American College of Cardiology/American Heart Association guidelines.[93] ## Prognosis[edit] Prognosis in heart failure can be assessed in multiple ways, including clinical prediction rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of clinical factors such as laboratory tests and blood pressure to estimate prognosis. Among several clinical prediction rules for prognosticating acute heart failure, the 'EFFECT rule' slightly outperformed other rules in stratifying people and identifying those at low risk of death during hospitalization or within 30 days.[95] Easy methods for identifying people that are low-risk are: * ADHERE Tree rule indicates that people with blood urea nitrogen < 43 mg/dl and systolic blood pressure at least 115 mm Hg have less than 10% chance of inpatient death or complications. * BWH rule indicates that people with systolic blood pressure over 90 mm Hg, respiratory rate of 30 or fewer breaths per minute, serum sodium over 135 mmol/l, and no new ST-T wave changes have less than 10% chance of inpatient death or complications. A very important method for assessing prognosis in people with advanced heart failure is cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to heart transplantation as an indicator of prognosis. CPX testing involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a VO2 max less than 12–14 cc/kg/min indicates a poor survival and suggests that the person may be a candidate for a heart transplant. People with a VO2 max <10 cc/kg/min have a clearly poorer prognosis. The most recent International Society for Heart and Lung Transplantation guidelines[96] also suggest two other parameters that can be used for evaluation of prognosis in advanced heart failure, the heart failure survival score and the use of a criterion of VE/VCO2 slope > 35 from the CPX test. The heart failure survival score is calculated using a combination of clinical predictors and the VO2 max from the CPX test. Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life.[97][98] With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%.[99] Around 18 of every 1000 persons will experience an ischemic stroke during the first year after diagnosis of HF. As the duration of follow-up increases, the stroke rate rises to nearly 50 strokes per 1000 cases of HF by 5 years.[100] ## Epidemiology[edit] In 2015, heart failure affected about 40 million people globally.[9] Overall, around 2% of adults have heart failure[23] and in those over the age of 65, this increases to 6–10%.[5][24] Above 75 years old, rates are greater than 10%.[23] Rates are predicted to increase.[23] Increasing rates are mostly because of increasing lifespan, but also because of increased risk factors (hypertension, diabetes, dyslipidemia, and obesity) and improved survival rates from other types of cardiovascular disease (myocardial infarction, valvular disease, and arrhythmias).[101][102][103] Heart failure is the leading cause of hospitalization in people older than 65.[104] ### United States[edit] In the United States, heart failure affects 5.8 million people, and each year 550,000 new cases are diagnosed.[105] In 2011, heart failure was the most common reason for hospitalization for adults aged 85 years and older, and the second-most common for adults aged 65–84 years.[106] An estimated one in five adults at age 40 will develop heart failure during their remaining lifetimes and about half of people who develop heart failure die within 5 years of diagnosis.[107] Heart failure is much higher in African Americans, Hispanics, Native Americans, and recent immigrants from the Eastern Bloc countries such as Russia. This high prevalence in these ethnic minority populations has been linked to high incidence of diabetes and hypertension. In many new immigrants to the U.S., the high prevalence of heart failure has largely been attributed to lack of preventive health care or substandard treatment.[108] Nearly one of every four people (24.7%) hospitalized in the U.S. with congestive heart failure are readmitted within 30 days.[109] Additionally, more than 50% of people seek readmission within 6 months after treatment and the average duration of hospital stay is 6 days. Heart failure is a leading cause of hospital readmissions in the U.S. People aged 65 and older were readmitted at a rate of 24.5 per 100 admissions in 2011. In the same year, people under Medicaid were readmitted at a rate of 30.4 per 100 admissions, and uninsured people were readmitted at a rate of 16.8 per 100 admissions. These are the highest readmission rates for both categories. Notably, heart failure was not among the top-10 conditions with the most 30-day readmissions among the privately insured.[110] ### United Kingdom[edit] In the UK, despite moderate improvements in prevention, heart failure rates have increased due to population growth and ageing.[111] Overall heart failure rates are similar to the four most common causes of cancer (breast, lung, prostate, and colon) combined.[111] People from deprived backgrounds are more likely to be diagnosed with heart failure and at a younger age.[111] ### Developing world[edit] In tropical countries, the most common cause of HF is valvular heart disease or some type of cardiomyopathy. As underdeveloped countries have become more affluent, the incidences of diabetes, hypertension, and obesity have increased, which have in turn raised the incidence of heart failure.[112] ### Sex[edit] Men have a higher incidence of heart failure, but the overall prevalence rate is similar in both sexes since women survive longer after the onset of heart failure.[113] Women tend to be older when diagnosed with heart failure (after menopause), they are more likely than men to have diastolic dysfunction, and seem to experience a lower overall quality of life than men after diagnosis.[113] ### Ethnicity[edit] Some sources state that people of Asian descent are at a higher risk of heart failure than other ethnic groups.[114] Other sources however have found that rates of heart failure are similar to rates found in other ethnic groups.[115] ## Economics[edit] In 2011, nonhypertensive heart failure was one of the 10 most expensive conditions seen during inpatient hospitalizations in the U.S., with aggregate inpatient hospital costs more than $10.5 billion.[116] Heart failure is associated with a high health expenditure, mostly because of the cost of hospitalizations; costs have been estimated to amount to 2% of the total budget of the National Health Service in the United Kingdom, and more than $35 billion in the United States.[117][118] ## Research directions[edit] Some low-quality evidence indicates that stem cell therapy may help.[119] Although this evidence positively indicated benefit, the evidence was of lower quality than other evidence that does not indicate benefit.[120] A 2016 Cochrane review found tentative evidence of longer life expectancy and improved left ventricular ejection fraction in persons treated with bone marrow-derived stem cells.[119] ## References[edit] 1. ^ "Living Well With Chronic Heart Failure" (PDF). 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Cardiology. 10 (2): 98–110. doi:10.1038/nrcardio.2012.178. PMC 3753073. PMID 23229137. 83. ^ Giallauria F, Vigorito C, Piepoli MF, Stewart Coats AJ (August 2014). "Effects of cardiac contractility modulation by non-excitatory electrical stimulation on exercise capacity and quality of life: an individual patient's data meta-analysis of randomized controlled trials". International Journal of Cardiology. 175 (2): 352–7. doi:10.1016/j.ijcard.2014.06.005. PMID 24975782. 84. ^ Borggrefe M, Burkhoff D (July 2012). "Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure". European Journal of Heart Failure. 14 (7): 703–12. doi:10.1093/eurjhf/hfs078. PMID 22696514. S2CID 10484257. 85. ^ Kuschyk J, Roeger S, Schneider R, Streitner F, Stach K, Rudic B, et al. (March 2015). "Efficacy and survival in patients with cardiac contractility modulation: long-term single center experience in 81 patients". International Journal of Cardiology. 183 (183C): 76–81. doi:10.1016/j.ijcard.2014.12.178. PMID 25662055. 86. ^ Kuschyk J (2014). "Der Besondere Stellenwert der Kardialen Kontraktilitätsmodulation in der Devicetherapie". Herzmedizin. Archived from the original on 5 July 2015. Retrieved 6 June 2014. 87. ^ Clinical trial number NCT01381172 for "Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure: FIX-HF-5C (FIX-HF-5C)" at ClinicalTrials.gov 88. ^ Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. (October 2013). "2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 128 (16): e240–327. doi:10.1161/CIR.0b013e31829e8776. PMID 23741058. 89. ^ Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, et al. (October 2013). "Cardiac-resynchronization therapy in heart failure with a narrow QRS complex" (PDF). The New England Journal of Medicine. 369 (15): 1395–405. doi:10.1056/NEJMoa1306687. PMID 23998714. 90. ^ Carrel T, Englberger L, Martinelli MV, Takala J, Boesch C, Sigurdadottir V, Gygax E, Kadner A, Mohacsi P (18 October 2012). "Continuous flow left ventricular assist devices: a valid option for heart failure patients". Swiss Medical Weekly. 142: w13701. doi:10.4414/smw.2012.13701. PMID 23135811. 91. ^ Lindenfeld J, Miller GG, Shakar SF, Zolty R, Lowes BD, Wolfel EE, et al. (December 2004). "Drug therapy in the heart transplant recipient: part I: cardiac rejection and immunosuppressive drugs". Circulation. 110 (24): 3734–40. doi:10.1161/01.cir.0000149745.83186.89. PMID 15596559. 92. ^ a b Kavalieratos D, Gelfman LP, Tycon LE, Riegel B, Bekelman DB, Ikejiani DZ, Goldstein N, Kimmel SE, Bakitas MA, Arnold RM (October 2017). "Palliative Care in Heart Failure: Rationale, Evidence, and Future Priorities". Journal of the American College of Cardiology. 70 (15): 1919–1930. doi:10.1016/j.jacc.2017.08.036. PMC 5731659. PMID 28982506. 93. ^ a b Adler ED, Goldfinger JZ, Kalman J, Park ME, Meier DE (December 2009). "Palliative care in the treatment of advanced heart failure". Circulation. 120 (25): 2597–606. doi:10.1161/CIRCULATIONAHA.109.869123. PMID 20026792. 94. ^ Kavalieratos D, Corbelli J, Zhang D, Dionne-Odom JN, Ernecoff NC, Hanmer J, et al. (November 2016). "Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis". JAMA. 316 (20): 2104–2114. doi:10.1001/jama.2016.16840. PMC 5226373. PMID 27893131. 95. ^ Auble TE, Hsieh M, McCausland JB, Yealy DM (August 2007). "Comparison of four clinical prediction rules for estimating risk in heart failure". Annals of Emergency Medicine. 50 (2): 127–35, 135.e1–2. doi:10.1016/j.annemergmed.2007.02.017. PMID 17449141. 96. ^ Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. (September 2006). "Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006". The Journal of Heart and Lung Transplantation. 25 (9): 1024–42. doi:10.1016/j.healun.2006.06.008. PMID 16962464. 97. ^ Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M (March 2002). "Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables". Heart. 87 (3): 235–41. doi:10.1136/heart.87.3.235. PMC 1767036. PMID 11847161. 98. ^ Hobbs FD, Kenkre JE, Roalfe AK, Davis RC, Hare R, Davies MK (December 2002). "Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population". European Heart Journal. 23 (23): 1867–76. doi:10.1053/euhj.2002.3255. PMID 12445536. 99. ^ Neubauer S (March 2007). "The failing heart--an engine out of fuel". The New England Journal of Medicine. 356 (11): 1140–51. doi:10.1056/NEJMra063052. PMID 17360992. S2CID 1481349. 100. ^ Witt BJ, Gami AS, Ballman KV, Brown RD, Meverden RA, Jacobsen SJ, Roger VL (August 2007). "The incidence of ischemic stroke in chronic heart failure: a meta-analysis". Journal of Cardiac Failure. 13 (6): 489–96. doi:10.1016/j.cardfail.2007.01.009. PMID 17675064. 101. ^ Mann DL, Chakinala M (2012). "Chapter 234. Heart Failure and Cor Pulmonale". Harrison's principles of internal medicine: Chapter 234. Heart Failure and Cor Pulmonale (18th ed.). New York: McGraw-Hill. ISBN 978-0-07-174889-6. 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"Heart Failure in South Asian Population". Management of Heart Failure. pp. 305–317. doi:10.1007/978-1-4471-6657-3_16. ISBN 978-1-4471-6656-6. 115. ^ Reyes EB, Ha JW, Firdaus I, Ghazi AM, Phrommintikul A, Sim D, et al. (November 2016). "Heart failure across Asia: Same healthcare burden but differences in organization of care". International Journal of Cardiology. 223: 163–167. doi:10.1016/j.ijcard.2016.07.256. PMID 27541646. 116. ^ Torio CM, Andrews RM. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011. HCUP Statistical Brief #160. Agency for Healthcare Research and Quality, Rockville, MD. August 2013. "Statistical Brief #160". Archived from the original on 14 March 2017. Retrieved 1 May 2017. 117. ^ Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ (June 2002). "The current cost of heart failure to the National Health Service in the UK". European Journal of Heart Failure. 4 (3): 361–71. doi:10.1016/S1388-9842(01)00198-2. PMID 12034163. S2CID 12765307. 118. ^ Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, et al. (January 2008). "Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee". Circulation. 117 (4): e25–146. doi:10.1161/CIRCULATIONAHA.107.187998. PMID 18086926. 119. ^ a b Fisher SA, Doree C, Mathur A, Taggart DP, Martin-Rendon E (December 2016). "Stem cell therapy for chronic ischaemic heart disease and congestive heart failure". The Cochrane Database of Systematic Reviews. 12: CD007888. doi:10.1002/14651858.CD007888.pub3. PMC 6463978. PMID 28012165. 120. ^ Nowbar AN, Mielewczik M, Karavassilis M, Dehbi HM, Shun-Shin MJ, Jones S, Howard JP, Cole GD, Francis DP (April 2014). "Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis". BMJ. 348: g2688. doi:10.1136/bmj.g2688. PMC 4002982. PMID 24778175. ## External links[edit] Wikimedia Commons has media related to Heart failure. * Heart failure, American Heart Association – information and resources for treating and living with heart failure * Heart Failure Matters – patient information website of the Heart Failure Association of the European Society of Cardiology * Heart failure in children by Great Ormond Street Hospital, London, UK * "Heart Failure". MedlinePlus. U.S. National Library of Medicine. Classification D * ICD-10: I50, I11.0, I13.0, I13.2, I97.1, P29.0 * ICD-9-CM: 428.0 * MeSH: D006333 * DiseasesDB: 16209 External resources * MedlinePlus: 000158 * Patient UK: Heart failure * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever * v * t * e Organ failure General * Heart failure * Respiratory failure * Liver failure * Acute * Chronic * Renal failure * Acute * Chronic * Encephalopathy Multiple * Multiple organ dysfunction syndrome Authority control * GND: 4024655-3 * NDL: 00571034 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Heart failure	c0023212	30,094	wikipedia	https://en.wikipedia.org/wiki/Heart_failure	2021-01-18T18:28:32	{"mesh": ["D006333"], "icd-9": ["428.0"], "icd-10": ["I50"], "wikidata": ["Q181754"]}
A rare non-syndromic central nervous system malformation characterized by complete or near-complete absence of the cerebellum with a normal sized posterior fossa, possibly accompanied by hypoplasia of the brainstem. The clinical picture is highly variable, but typically includes ataxia, dysarthria, tremor, dysmetria, dysdiadochokinesia, and oculomotor abnormalities, in addition to impaired mental, motor, and language development and intellectual disability. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Isolated cerebellar agenesis	c0266470	30,095	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1398	2021-01-23T18:23:44	{"mesh": ["C562568"], "umls": ["C0266470", "C0344488"], "icd-10": ["Q04.3"], "synonyms": ["Near total absence of cerebellum", "Subtotal absence of cerebellum"]}
A number sign (#) is used with this entry because of evidence that RAS-associated autoimmune leukoproliferative disorder (RALD) is caused by somatic mutation in the NRAS gene (164790) or the KRAS gene (190070) on chromosome 12p12. One patient with somatic mutation in the NRAS gene has been reported. Description RAS-associated leukoproliferative disorder is characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia. Laboratory studies show an expansion of lymphocytes due to defective apoptosis, as well as significant autoantibodies. Some patients have recurrent infections, and there may be an increased risk of hematologic malignancy (summary by Oliveira, 2013 and Niemela et al., 2010). The disorder shows significant overlap with autoimmune lymphoproliferative syndrome (ALPS; 601859) and was originally designated ALPS IV. Clinical Features Oliveira et al. (2007) reported a 49-year-old patient with autoimmune lymphoproliferative syndrome who had a lifelong overexpansion of lymphocytes and a history of childhood leukemia and early adulthood lymphoma, both successfully treated. There were no developmental defects. Laboratory studies showed increased serum CD4-/CD8- (double-negative) alpha/beta T cells and lymph node follicular hyperplasia. There was no evidence of CD95 (134637)-mediated apoptosis, but the patient's lymphocytes resisted death by IL2 (147680) withdrawal, indicating a specific defect in lymphocyte apoptosis. Further studies of the patient's lymphocytes showed a decrease of the proapoptotic protein BIM (BCL2L11; 603827), which is critical for cytokine withdrawal-induced mitochondrial apoptosis. Niemela et al. (2010) reported 2 unrelated Caucasian girls with RALD presenting in childhood. One had lymphadenopathy, splenomegaly, and recurrent upper respiratory infections. She developed several autoimmune conditions, including hemolytic anemia and thrombocytopenia. Laboratory studies showed hypergammaglobulinemia, B-cell lymphocytosis, monocytosis, and autoantibodies. Alpha/beta CD4-/CD8- T cells were not increased. She continued to have recurrent inflammatory episodes affecting the respiratory tract, but without documentation of an infectious agent. She died at age 13 years after a fever and cardiac arrest. The second patient presented at age 5 years with acute viral infections and was found to have splenomegaly, neutropenia, monocytosis, thrombocytopenia, and a facial rash. Throughout childhood, she had recurrent vasculitis of the lower limbs and developed pancytopenia and lymphadenopathy. Laboratory studies showed autoantibodies and hypergammaglobulinemia. Her psychomotor development was normal. Patient T cells showed resistance to apoptosis after IL2 withdrawal, and BIM levels were reduced. Takagi et al. (2011) reported 2 unrelated children who presented with RALD at ages 9 and 5 months, respectively. Both had significant lymphadenopathy and hepatosplenomegaly, hemolytic anemia, autoimmune thrombocytopenia, hypergammaglobulinemia, and autoantibodies. Neither had a significant increase of CD4-/CD8- alpha/beta T cells, but T cells from both patients showed apoptotic resistance to IL2 withdrawal. Western blot analysis showed decreased expression of BIM in activated T cells and B cells. Molecular Genetics In a patient with ALPS type IV, Oliveira et al. (2007) identified a heterozygous mutation in the NRAS gene (G13D; 164790.0003). The mutation was found in the patient's lymphoblasts, peripheral blood mononuclear cells, monocytes, EBV-transformed B cells, and buccal epithelial cells. It was not present in the patient's unaffected relatives, suggesting de novo occurrence. In vitro functional expression studies showed that the G13D mutation caused increased activation of NRAS and augmented downstream signaling, resulting in downregulation of the proapoptotic factor BIM. Niemela et al. (2010) stated that the NRAS mutation found by Oliveira et al. (2007) was a somatic mutation. In 2 unrelated girls with RALD, Niemela et al. (2010) identified 2 different somatic heterozygous gain-of-function mutations in the KRAS gene (G12D, 190070.0005 and G13C, 190070.0023). In vitro studies indicated that the activating KRAS mutations impaired cytokine withdrawal-induced T-cell apoptosis through suppression of the proapoptotic protein BIM, and facilitated lymphocyte proliferation through downregulation of CDKN1B (600778). In 2 unrelated children with RALD, Takagi et al. (2011) identified a somatic heterozygous mutation in the KRAS gene (G13D; 190070.0003). The mutation was seen exclusively in the hematopoietic cell line, including granulocytes, monocytes, and lymphocytes. INHERITANCE \- Autosomal dominant RESPIRATORY \- Recurrent respiratory infections (in some patients) ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly HEMATOLOGY \- Hemolytic anemia \- Autoimmune thrombocytopenia \- Pancytopenia IMMUNOLOGY \- Lymphadenopathy \- Recurrent infections (in some patients) \- Autoimmune disorders \- Autoantibodies \- Hypergammaglobulinemia \- Monocytosis \- B-cell lymphocytosis \- Neutropenia \- Alpha/beta, CD4-/CD8- T cells are minimally or not increased \- Defective lymphocyte apoptosis NEOPLASIA \- Increased risk of hematologic malignancy (1 patient) MISCELLANEOUS \- Onset in childhood \- Caused by somatic mutations MOLECULAR BASIS \- Caused by somatic mutation in the NRAS proto-oncogene, GTPase gene (NRAS, 164790.0003 ) \- Caused by somatic mutation in the KRAS proto-oncogene, GTPase gene (KRAS, 190070.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER	c2674723	30,096	omim	https://www.omim.org/entry/614470	2019-09-22T15:55:09	{"doid": ["0110117"], "omim": ["614470"], "orphanet": ["268114"], "synonyms": ["AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE IV", "Alternative titles", "RALD"]}
Not to be confused with poliomyelitis. Polymyositis Micrograph of polymyositis. Muscle biopsy. H&E stain. SpecialtyRheumatology Polymyositis (PM) is a type of chronic inflammation of the muscles (inflammatory myopathy) related to dermatomyositis and inclusion body myositis. Its name means "inflammation of many muscles" (poly- \+ myos- \+ -itis). The inflammation of polymyositis is mainly found in the endomysial layer of skeletal muscle, where as dermatomyositis is characterized primarily by inflammation of the perimysial layer of skeletal muscles.[1] ## Contents * 1 Signs and symptoms * 1.1 Associated illnesses * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 Notable cases * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] The hallmark of polymyositis is weakness and/or loss of muscle mass in the proximal musculature, as well as flexion of the neck and torso.[1] These symptoms can be associated with marked pain in these areas as well. The hip extensors are often severely affected, leading to particular difficulty in climbing stairs and rising from a seated position. The skin involvement of dermatomyositis is absent in polymyositis. Dysphagia (difficulty swallowing) or other problems with esophageal motility occur in as many as 1/3 of patients. Low grade fever and enlarged lymph nodes may be present. Foot drop in one or both feet can be a symptom of advanced polymyositis and inclusion body myositis. The systemic involvement of polymyositis includes interstitial lung disease (ILD) and heart disease, such as heart failure and conduction abnormalities.[2] Polymyositis tends to become evident in adulthood, presenting with bilateral proximal muscle weakness often noted in the upper legs due to early fatigue while walking. Sometimes the weakness presents itself as an inability to rise from a seated position without help or an inability to raise one's arms above one's head. The weakness is generally progressive, accompanied by lymphocytic inflammation (mainly cytotoxic T cells).[citation needed] ### Associated illnesses[edit] Polymyositis and the associated inflammatory myopathies have an associated increased risk of cancer.[3] The features they found associated with an increased risk of cancer was older age, age greater than 45, male sex, difficulty swallowing, death of skin cells, cutaneous vasculitis, rapid onset of myositis (<4 weeks), elevated creatine kinase, higher erythrocyte sedimentation rate and higher C-reactive protein levels. Several factors were associated with lower-than-average risk, including the presence of interstitial lung disease, joint inflammation/joint pain, Raynaud's syndrome, or anti-Jo-1 antibody.[3] The malignancies that are associated are nasopharyngeal cancer, lung cancer, non-Hodgkin's lymphoma and bladder cancer, amongst others.[4] Cardiac involvement manifests itself typically as heart failure, and is present in up to 77% of patients.[2] Interstitial lung disease is found in up to 65% of patients with polymyositis, as defined by HRCT or restrictive ventilatory defects compatible with interstitial lung disease.[5] ## Causes[edit] Polymyositis is an inflammatory myopathy mediated by cytotoxic T cells with an as yet unknown autoantigen, while dermatomyositis is a humorally mediated angiopathy resulting in myositis and a typical dermatitis.[6] The cause of polymyositis is unknown and may involve viruses and autoimmune factors. Cancer may trigger polymyositis and dermatomyositis, possibly through an immune reaction against cancer that also attacks a component of muscles.[7] There is tentative evidence of an association with celiac disease.[8] ## Diagnosis[edit] Diagnosis is fourfold: History and physical examination, elevation of creatine kinase, electromyograph (EMG) alteration, and a positive muscle biopsy.[9] The hallmark clinical feature of polymyositis is proximal muscle weakness, with less important findings being muscle pain and dysphagia. Cardiac and pulmonary findings will be present in approximately 25% of cases of patients with polymyositis.[citation needed] Sporadic inclusion body myositis (sIBM): IBM is often confused with (misdiagnosed as) polymyositis or dermatomyositis that does not respond to treatment is likely IBM. sIBM comes on over months to years; polymyositis comes on over weeks to months. Polymyositis tends to respond well to treatment, at least initially; IBM does not.[citation needed] ## Treatment[edit] The first line treatment for polymyositis is corticosteroids. Specialized exercise therapy may supplement treatment to enhance quality of life.[citation needed] ## Epidemiology[edit] Polymyositis, like dermatomyositis, strikes females with greater frequency than males.[citation needed] ## Notable cases[edit] * Dan Christensen, painter of abstract art. Died due to heart failure caused by polymyositis.[10] * Robert Erickson, American composer and teacher who was a leading modernist exponent of "12-tone" composition. Died from the effects of polymyositis.[11] * David Lean, film director.[12][13] * Eric Samuelsen, playwright.[citation needed] * Victor Manuel Resendiz Ruiz, wrestler.[citation needed] ## See also[edit] * Limb girdle syndrome ## References[edit] 1. ^ a b Strauss KW, Gonzalez-Buritica H, Khamashta MA, Hughes GR (July 1989). "Polymyositis-dermatomyositis: a clinical review". Postgraduate Medical Journal. 65 (765): 437–43. doi:10.1136/pgmj.65.765.437. PMC 2429417. PMID 2690042. 2. ^ a b Zhang L, Wang GC, Ma L, Zu N (November 2012). "Cardiac involvement in adult polymyositis or dermatomyositis: a systematic review". Clinical Cardiology. 35 (11): 686–91. doi:10.1002/clc.22026. PMC 6652370. PMID 22847365. 3. ^ a b Xin Lu; Hanbo Yang; Xiaoming Shu; Fang Chen; Yinli Zhang; Sigong Zhang; Qinglin Peng; Xiaolan Tian; Guochun Wang (2014). "Factors Predicting Malignancy in Patients with Polymyositis and Dermatomyositis: A Systematic Review and Meta-Analysis". PLOS ONE. 9 (4): e94128. Bibcode:2014PLoSO...994128L. doi:10.1371/journal.pone.0094128. PMC 3979740. PMID 24713868. 4. ^ Hill, C.L.; Zhang, Y.; Sigurgeirsson, B.; Pukkala, E.; Mellemkjaer, L.; Airio, A.; Evans, S.R.; Felson, D.T. (January 2001). "Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study". Lancet. 357 (9250): 96–100. doi:10.1016/S0140-6736(00)03540-6. PMID 11197446. S2CID 35258253. Retrieved 20 April 2015. 5. ^ Fathi M, Dastmalchi M, Rasmussen E, Lundberg IE, Tornling G (March 2004). "Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis". Annals of the Rheumatic Diseases. 63 (3): 297–301. doi:10.1136/ard.2003.006122. PMC 1754925. PMID 14962966. 6. ^ Gerald J D Hengstman, Baziel G M van Engelen (2004). "Polymyositis, invasion of non-necrotic muscle fibres, and the art of repetition". British Medical Journal. 329 (7480): 1464–1467. doi:10.1136/bmj.329.7480.1464. PMC 535982. PMID 15604185. 7. ^ Hajj-ali, Rula A. (August 2013). "Polymyositis and Dermatomyositis". Merck Manual Home Edition. Archived from the original on 19 April 2015. Retrieved 20 April 2015. 8. ^ Shapiro M, Blanco DA (2017). "Neurological Complications of Gastrointestinal Disease". Semin Pediatr Neurol (Review). 24 (1): 43–53. doi:10.1016/j.spen.2017.02.001. PMID 28779865. 9. ^ Scola RH, Werneck LC, Prevedello DM, Toderke EL, Iwamoto FM (September 2000). "Diagnosis of dermatomyositis and polymyositis: a study of 102 cases". Arquivos de Neuro-Psiquiatria. 58 (3B): 789–99. doi:10.1590/S0004-282X2000000500001. PMID 11018813. 10. ^ "Dan Christensen, 64, Painter of Abstract Art, Dies". The New York Times. 27 January 2007. Archived from the original on 5 June 2015. Retrieved 20 April 2015. 11. ^ "Obituary - Robert Erickson". SF Gate. 29 April 1997. Archived from the original on 1 January 2015. Retrieved 20 April 2015. 12. ^ Stevens, Jr., George (2006). Conversations with the Great Moviemakers of Hollywood's Golden Age at the American Film Institute. Knopf. p. 427. ISBN 978-1-4000-4054-4. 13. ^ Brownlow, Kevin (1996). David Lean: A Biography. Macmillan. pp. 1466–1467. ISBN 978-1-4668-3237-4. Archived from the original on 13 January 2018. Retrieved 20 April 2015. ## External links[edit] Classification D * ICD-10: M33.2 * ICD-9-CM: 710.4 * MeSH: D017285 * DiseasesDB: 10343 External resources * MedlinePlus: 000428 * eMedicine: med/3441 emerg/474 * Scholia: Q980926 * v * t * e Systemic connective tissue disorders General Systemic lupus erythematosus * Drug-induced SLE * Libman–Sacks endocarditis Inflammatory myopathy * Myositis * Dermatopolymyositis * Dermatomyositis/Juvenile dermatomyositis * Polymyositis* Inclusion body myositis Scleroderma * Systemic scleroderma * Progressive systemic sclerosis * CREST syndrome * Overlap syndrome / Mixed connective tissue disease Other hypersensitivity/autoimmune * Sjögren syndrome Other * Behçet's disease * Polymyalgia rheumatica * Eosinophilic fasciitis * Eosinophilia–myalgia syndrome * fibrillin * Marfan syndrome * Congenital contractural arachnodactyly [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Polymyositis	c0085655	30,097	wikipedia	https://en.wikipedia.org/wiki/Polymyositis	2021-01-18T18:56:21	{"gard": ["7425"], "mesh": ["D017285"], "umls": ["C0085655"], "icd-9": ["710.4"], "icd-10": ["M33.2"], "orphanet": ["732"], "wikidata": ["Q980926"]}
Hodgkin lymphoma (HL) is a heterogeneous group of malignant lymphoid neoplasms of B-cell origin characterized histologically by the presence of Hodgkin and Reed-Sternberg (HRS) cells in the vast majority of cases. ## Epidemiology HL is an uncommon cancer with an incidence of about 1/40,000 in North America and Europe. There are about 8500 new cases reported in the U.S. each year. ## Clinical description HL is comprised of 2 major forms: classical Hodgkin lymphoma (CHL; see this term), seen in 95% of all HL cases, and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL; see this term), seen in only 5% of all HL cases. Disease onset occurs most frequently in young adults (age 15-35) followed by older adults (over the age of 55) and usually begins with the painless swelling of a lymph node in the upper body. Disease can spread to multiple lymph node regions or lymphoid structures and associated systemic symptoms (weight loss > 10% of baseline, fevers, night sweats) are observed in about 20% of patients. ## Etiology The exact cause is unknown but immunological, genetic and environmental factors are thought to be involved. ## Management and treatment Treatment with radiotherapy and systemic chemotherapy leads to a very good prognosis. Follow-up physical exams, blood tests and x-rays are needed to check for recurrence and check for any long-term side effects of the toxic treatments. Possible long-term side effects include secondary cancers, infertility, reduced immunity, thyroid problems, heart disease and stroke. ## Prognosis The international prognostic score (IPS) is a score given based on the presence of 7 risk factors (male sex, >45 years of age, stage 4 disease, serum albumin <4g/dl, hemoglobin <10.5 g/l, lymphocytopenia and WBC count >15,000/mm3) at the time of diagnosis. The more factors present, the less favorable the prognosis. The cure rates are 90% for early-stage HL and 70% for advance stage HL. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hodgkin lymphoma	c0019829	30,098	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98293	2021-01-23T17:33:38	{"gard": ["2714"], "mesh": ["D006689"], "umls": ["C0019829"]}
Cystic eyeball SpecialtyMedical genetics Congenital cystic eye (also known as CCE or cystic eyeball) is an extremely rare ocular malformation where the eye fails to develop correctly in utero and is replaced by benign, fluid-filled tissue.[1] Its incidence is unknown, due to the very small number of cases reported. An audit by Duke-Elder of the medical literature from 1880 to 1963 discovered only 28 cases. The term was coined in 1937 by the renowned ophthalmologist Ida Mann.[2] Embryologically, the defect is thought to occur around day 35 of gestation, when the vesicle fails to invaginate. Dysgenesis of the vesicle later in development may result in coloboma, a separate and less severe malformation of the ocular structures. CCE is almost always unilateral, but at least 2 cases of bilateral involvement have been described. Patients may also present with skin appendages attached to the skin surrounding the eyes. Association with intracranial anomalies has been reported.[3] ## Treatment[edit] Treatment of CCE is usually by enucleation, followed by insertion of an ocular implant and prosthesis. ## References[edit] 1. ^ Gupta, P; Malik, KP; Goel, R (Jul 3, 2003). "Congenital cystic eye with multiple dermal appendages: a case report". BMC Ophthalmology. 3: 7. doi:10.1186/1471-2415-3-7. PMC 166276. PMID 12841852. 2. ^ Pillai, AM; Rema; Sambasivan, M (Mar–Apr 1987). "Congenital cystic eye--a case report with CT scan". Indian Journal of Ophthalmology. 35 (2): 88–91. PMID 3450626. 3. ^ Tsitouridis, I; Michaelides, M; Tsantiridis, C; Spyridi, S; Arvanity, M; Efstratiou, I (June 2010). "Congenital cystic eye with multiple dermal appendages and intracranial congenital anomalies". Diagnostic and Interventional Radiology (Ankara, Turkey). 16 (2): 116–21. doi:10.4261/1305-3825.DIR.2054-08.1. PMID 19847771. ## External links[edit] Classification D * ICD-10: Q11.0 * ICD-9-CM: 743.03 * v * t * e Congenital malformations and deformations of eyes Adnexa Eyelid * Ptosis * Ectropion * Entropion * Distichia * Blepharophimosis * Ablepharon * Marcus Gunn phenomenon Lacrimal apparatus * Congenital lacrimal duct obstruction Globe Entire eye * Anophthalmia (Cystic eyeball, Cryptophthalmos) * Microphthalmia Lens * Ectopia lentis * Aphakia Iris * Aniridia Anterior segment * Axenfeld–Rieger syndrome Cornea * Keratoglobus * Megalocornea Other * Buphthalmos * Coloboma (Coloboma of optic nerve) * Hydrophthalmos * Norrie disease 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 [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Cystic eyeball	c0158543	30,099	wikipedia	https://en.wikipedia.org/wiki/Cystic_eyeball	2021-01-18T18:33:18	{"gard": ["10617"], "icd-9": ["743.03"], "icd-10": ["Q11.0"], "wikidata": ["Q5201209"]}

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