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Multiple endocrine neoplasia (MEN) is a group of rare inherited cancer syndromes characterized by the development of two or more endocrine gland tumors, sometimes with tumor development in other tissues or organs.
## Epidemiology
The overall prevalence and incidence of MEN are not known. The prevalence of MEN1 is estimated to be approximately 1/10,000 to 1/30,000, while the total prevalence of MEN2 variants is approximately 1/35,000. MEN4 is extremely rare. The incidence of MEN1 has been estimated from random postmortem studies to be 0.25%, and to be 1-18% in patients with primary hyperparathyroidism, 16 to 38% in patients with gastrinomas, and less than 3% in patients with pituitary tumors.
## Clinical description
Multiple endocrine neoplasia syndromes can develop in patients of all ages: from infants to elderly patients over 70 years of age. Manifestations vary depending on the affected endocrine glands. There are three types of MEN (multiple endocrine neoplasia types 1, 2, and 4; see these terms) based on the underlying genetic abnormalities, the endocrine glands involved and the clinical manifestations. Each type includes a different combination of pituitary, pancreatic, parathyroid, medullary, thyroid, and adrenal tumors. MEN1 is characterized by parathyroid, pituitary gland, and pancreatic tumors. MEN2 is divided into two subtypes: MEN2A characterized by medullary thyroid carcinoma (see this term) in combination with pheochromocytoma (see this term) and primary mild hyperparathyroidism; and MEN2B (formerly MEN3), a rare form, involving medullary thyroid carcinoma, pheochromocytoma, mucosal ganglioneuromas and marfanoid habitus. MEN4 involves the development of parathyroid and anterior pituitary tumors.
## Etiology
MEN1 is caused by inactivating mutations in the MEN1 gene (11q13), and in some patients by mutations in the cyclin-dependent kinase inhibitor genes (CDKN1A, CDKN2B, CDKN2C). MEN2A and MEN2B are due to activating mutations in the RET gene (10q11.2), and MEN4 to inactivating mutations in the CDKN1B gene (12p13.1-p12). Patients with MEN1-like phenotypes (primary hyperparathyroidism associated with various tumors and lesions of the pituitary gland, pancreas, and duodenum) have also been found to have inactivating germline heterozygote mutation in CDKN1B.
## Genetic counseling
MEN follows an autosomal dominant pattern of inheritance and some sporadic cases are reported. First-degree relatives have a 50% risk of developing the disorder, making appropriate genetic counseling very important in affected families. Biochemical and genetic screening may be suggested to family members.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Multiple endocrine neoplasia
|
c0027662
| 7,500 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276161
| 2021-01-23T17:44:30 |
{"mesh": ["D009377"], "umls": ["C0027662"], "icd-10": ["D44.8"], "synonyms": ["MEN"]}
|
Thiamine-responsive maple syrup urine disease (thiamine-responsive MSUD) is a less severe variant of MSUD (see this term) that manifests with a phenotype similar to intermediate MSUD (see this term) but that responds positively to treatment with thiamine.
## Epidemiology
MSUD has an estimated incidence of 1/150,000 live births. The thiamine-responsive type appears to be very rare.
## Clinical description
Thiamine-responsive MSUD is poorly characterized. It appears to usually present after infancy with a phenotype very similar to that seen in intermediate MSUD (see this term). Manifestations include feeding problems, poor growth, maple syrup odor in urine and developmental delay. Older children usually present with learning difficulties. Like classic MSUD (see this term), physiological stress can result in acute decompensation with anorexia, nausea, vomiting (at all ages), ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, acute / focal dystonia and choreoathetosis (in adults) that can progress to stupor, coma and cerebral edema, if untreated. Thiamine (doses of 10-1000 mg per day) has improved the leucine tolerance in the few reported cases of this MSUD subtype, but some dietary branched-chain amino-acid (BCAA) restriction remains necessary.
## Etiology
MSUD is due to mutations in the genes encoding 3 of the 4 subunits of branched-chain 2-ketoacid dehydrogenase (BCKAD) complex. The genes are BCKDHA (19q13.1-q13.2), encoding E1a; BCKDHB (6q14.1), encoding E1b; and DBT (1p31), encoding E2 respectively. Mutations lead to an accumulation of BCAAs (especially leucine) and branched-chain alpha-ketoacids. In thiamine-responsive MSUD, mutations in DBT predominate.
## Genetic counseling
Inheritance is autosomal recessive and genetic counseling is possible.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Thiamine-responsive maple syrup urine disease
|
c0751285
| 7,501 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268184
| 2021-01-23T17:38:20 |
{"mesh": ["D008375"], "omim": ["248600"], "umls": ["C0751285"], "icd-10": ["E71.0"], "synonyms": ["Thiamine-responsive BCKD deficiency", "Thiamine-responsive MSUD", "Thiamine-responsive branched-chain alpha-ketoacid dehydrogenase deficiency"]}
|
Dislocation of the hip-dysmorphism syndrome is a rare multiple congenital anomalies syndrome characterized by bilateral congenital dislocation of the hip, characteristic facial features (flat mid-face, hypertelorism, epicanthus, puffiness around the eyes, broad nasal bridge, carp-shaped mouth), and joint hyperextensibility. Congenital heart defects, congenital dislocation of the knee, congenital inguinal hernia, and vesicoureteric reflux have also been reported. There have been no further descriptions in the literature since 1995.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dislocation of the hip-dysmorphism syndrome
|
c1832353
| 7,502 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2412
| 2021-01-23T18:31:16 |
{"gard": ["1428"], "mesh": ["C563315"], "omim": ["601450"], "icd-10": ["Q87.2"], "synonyms": ["Collins-Pope syndrome"]}
|
A malformation syndrome reported in offspring (children and grandchildren) of women exposed to diethylstilbestrol (DES) during pregnancy and is characterized by reproductive tract malformations, decreased fertility and increased risk of developing clear cell carcinoma of the vagina and cervix in young women. Reproductive malformations reported in DES syndrome include small, T-shaped uteri and other uterotubal anomalies that increase the risk of miscarriages in women and epididymal cysts, microphallus, cryptorchidism, or testicular hypoplasia in men. DES, a synthetic nonsteroidal estrogen was widely prescribed from 1940-1970 to prevent miscarriage.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Diethylstilbestrol syndrome
|
c0853695
| 7,503 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1916
| 2021-01-23T18:44:38 |
{"umls": ["C0853695"], "icd-10": ["Q86.8"], "synonyms": ["DES embryofetopathy", "DES syndrome", "Diethylstilbestrol embryofetopathy", "Distilbene embryofetopathy"]}
|
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset progressive myopathy characterized by progressive eyelid ptosis, dysphagia, dysarthria and proximal limb weakness.
## Epidemiology
OPMD is seen worldwide with varying prevalence rates. The estimated prevalence rate in Europe is 1/200,000-1/100,000. The highest prevalence rate of 1/1,000 is found in French Canadians in Quebec and 1/600 in Israel's Bukharan Jews.
## Clinical description
Disease onset occurs in the fifth to sixth decade of life. Early signs include ptosis, limb weakness and dysphagia. Symptoms usually begin after the age of 45 years, and ptosis is the most common presenting feature. Other signs that occur as the disease progresses include tongue weakness and atrophy, proximal upper and lower extremity weakness, dysphonia, dysarthria, facial muscle weakness, and limitation of upward gaze. In several cases, limb weakness has preceded dysphagia. In 5-10% of patients, the disease is more severe, with ptosis and dysphagia presenting before the age of 45 and incapacitating distal leg weakness occurring before the age of 60. The manifestations of autosomal recessive OPMD usually present later (after the age of 60) than those of the autosomal dominant form.
## Etiology
OPMD is caused by an expansion of the polyalanine tract in the gene PABPN1 (14q11.2), which leads to overexpression of a mutant protein and consequently to the accumulation of nuclear aggregates in the muscles.
## Diagnostic methods
OPMD is diagnosed by genetic confirmation of a mutation in the PABPN1 gene. Supportive evidence comes from finding tubulofilamentous inclusions in the nuclei of myocytes (intranuclear inclusions) using electron microscopy, as well as muscle fibers containing rimmed vacuoles, but a muscle biopsy is not needed for diagnosis. Creatine kinase (CK) levels are slightly elevated and electromyogram (EMG) studies may suggest a mild myopathic process.
## Differential diagnosis
Differential diagnoses include oculopharyngodistal myopathy, myasthenia gravis, Steinert myotonic dystrophy, proximal myotonic myopathy, congenital fibrosis of extraocular muscles, blepharophimosis-epicanthus inversus-ptosis syndrome (see these terms), autosomal dominant distal myopathy, and mitochondrial myopathy.
## Antenatal diagnosis
Prenatal diagnosis is possible, but as this condition presents in adulthood, it is very rarely performed.
## Genetic counseling
OPMD is inherited both autosomal dominantly (in most cases) and recessively. Genetic counseling is possible when a PABPN1 mutation has been identified in a family.
## Management and treatment
No pharmacological treatment is presently available, but surgical treatments are offered that can help with ptosis and dysphagia. A blepharoplasty can treat ptosis when the eyelids cover more than 50% of the pupils or when neck pain is present. A cricopharyngeal myotomy can be performed to achieve normal swallowing, but dysphagia usually recurs years after surgery. The intake of dietary supplements and a diet of foods that are soft and easy to swallow are often necessary. Some patients may need a wheelchair if muscle atrophy is severe.
## Prognosis
Ptosis and dysphagia typically recur within five to fifteen years after surgery. There is usually no decrease in life expectancy, but quality of life can be reduced in those where the disease is debilitating. Death is usually due to aspiration pneumonia or malnutrition (with severe weight loss) in elderly patients.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Oculopharyngeal muscular dystrophy
|
c0270952
| 7,504 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=270
| 2021-01-23T18:22:26 |
{"gard": ["7245"], "mesh": ["D039141"], "omim": ["164300"], "umls": ["C0270952"], "icd-10": ["G71.0"], "synonyms": ["OPMD"]}
|
Idiopathic pulmonary artery dilatation is a rare developmental defect during embryogenesis characterized by the dilatation of the main pulmonary artery, with or without dilatation of the right and left pulmonary artery branches, and not attributed to any other cardiac, pulmonary and/or arterial wall disease. It may present with exertional dyspnea, fatigue, cough, hemoptysis, palpitation and chest pain, but may also be asymptomatic. In serious cases, trachea constriction due to postural changes may lead to attacks of cyanosis with severe dyspnea. Sudden cardiac death has been reported in some cases.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Idiopathic pulmonary artery dilatation
|
None
| 7,505 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1676
| 2021-01-23T18:15:44 |
{"icd-10": ["E25.7"]}
|
A rare, genetic, macular dystrophy characterized by blurred vision, metamorphopsia and mild visual impairment secondary to a slightly elevated, yellow, egg yolk-like lesion located in the foveal or parafoveal region.
## Epidemiology
The prevalence of AOFVD is unknown.
## Clinical description
The clinical onset is typically between the fourth and sixth decade of life. In the early stages of AOFVD, patients are visually asymptomatic or have mild complaints of scotoma, visual blur or metamorphopsia in one or both eyes. The visual acuity usually ranges from 20/50 to 20/25. As the disease progresses, vision loss may become more severe. Choroidal neovascularization (CNV) or central retinal pigment epithelium (RPE) atrophy may result. Color vision has been reported to be slightly impaired (tritan defect).
## Etiology
The mechanism underlying the physiopathology of AOFVD is still unknown but it has been postulated that there is an abnormal accumulation of lipofuscin that may be caused by the increased workload of metabolism and phagocytosis on the RPE cells in conjunction with other disease-related factors (such as age, genetic predisposition, and environmental causes). As a result, the RPE layer is separated from the photoreceptor layer by hyper-reflective material. Mutations in the genes BEST1 (11q12), PRPH2 (6p21.1) or IMPG1 (6q14.2-q15) (encoding bestrophin-1, peripherin and SPACR respectively) have been found in some individuals with AOFVD.D.
## Diagnostic methods
Diagnosis of AOFVD relies on complete ophthalmologic examination, including measurement of best-corrected visual acuity (values range between 20/20-20/100), fundus biomicroscopy, fundus autofluorescence (FAF) imaging, and fluorescein angiography of optical coherent tomography when choroidal neovascularization is suspected. The minimal criteria for AOFVD diagnosis is the presence of a macular round, yellowish, more or less homogeneous lesion with fundus examination, showing hyper-autofluorescence. Electrooculogram (EOG) and electroretinogram (ERG) show normal or subnormal results (normal Arden ratio). Optical coherence tomography (OCT) reveals a vitelliform lesion located at the level of RPE or between the RPE and photoreceptors. This technique is extremely helpful in differentiating AOFVD from age-related macular degeneration (AMD; see this term).
## Differential diagnosis
The differential diagnosis of AOFVD includes Best vitelliform macular dystrophy, Stargardt disease, central areolar choroidal dystrophy, central serous retinopathy (CSR), pigmented epithelial detachment (PED), basal laminar drusen, acute exudative polymorphous vitelliform maculopathy (AEPVM) (see these terms) and occult CNV secondary to AMD.
## Genetic counseling
An autosomal dominant inheritance with variable expression and incomplete penetrance is suggested but AOFVD can also be sporadic without evidence of a familial inheritance pattern.
## Management and treatment
There is no effective therapy for AOVFD and patients should be managed with a comprehensive eye examination, including dilation, once or twice a year to rule out any possible complications, such as CNV, full-thickness macular holes, or retinal detachments. If vision is impaired, patients should be referred for low vision testing and rehabilitation. Ranibizumab intravitreal injections may be effective in the short-term.
## Prognosis
The visual prognosis of AOVFD is relatively good because the disease typically causes slow progressive vision loss, and most patients maintain decent vision in at least one eye until very late in the disease evolution. The vitelliform lesion typically disappears later in life; however, vision loss, development of a full-thickness macular hole or a retinal detachment in the late atrophic stages of the disease may be observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Adult-onset foveomacular vitelliform dystrophy
|
c1842914
| 7,506 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99000
| 2021-01-23T18:59:14 |
{"gard": ["10909"], "mesh": ["D057826"], "omim": ["153840", "608161", "616151", "616152"], "umls": ["C1842914"], "icd-10": ["H35.5"], "synonyms": ["AOFMD", "AVMD", "Adult-onset foveomacular dystrophy", "Adult-onset foveomacular dystrophy with choroidal neovascularization", "Adult-onset vitelliform macular dystrophy", "Gass disease", "Pseudo-Best disease", "Pseudo-vitelliform macular dystrophy"]}
|
Painful orbital and systemic neurofibromas-marfanoid habitus syndrome is a rare, benign, peripheral nerve sheath tumor disorder characterized by multiple, painful, mucin-rich plexiform neurofibromas located in the orbits, cranium, large spinal nerves and mucosa, associated with a marfanoid habitus, enlarged corneal nerves, congenital neuronal migration anomalies and facial dysmorphism which includes ptosis, proptosis, prominent nose, full lips, gingival hyperplasia, and multiple subcutaneous and submucosal nodules in the lips and sublingual zone.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Painful orbital and systemic neurofibromas-marfanoid habitus syndrome
|
None
| 7,507 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300501
| 2021-01-23T18:10:12 |
{"gard": ["11006"]}
|
A number sign (#) is used with this entry because of evidence that Mitchell-Riley syndrome (MTCHRS) is caused by homozygous or compound heterozygous mutation in the RFX6 gene (612659) on chromosome 6q22.
Description
Mitchell-Riley syndrome is characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia. There is considerable phenotypic overlap between Mitchell-Riley syndrome and Martinez-Frias syndrome (601346), the latter being characterized by the features of the Mitchell-Riley syndrome except for neonatal diabetes, and including tracheoesophageal fistula in some patients (Smith et al., 2010).
Clinical Features
Mitchell et al. (2004) described 5 infants, including a brother and sister born of first-cousin Pakistani parents (family 1), a brother and sister born of nonconsanguineous Asian parents (family 2), and an unrelated girl conceived by in vitro fertilization with a donated egg, who presented with neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder. There were no dysmorphic features. Both pairs of sibs died in the first year of life despite aggressive medical management, but the unrelated girl had a milder form and was surviving free of insulin at 1 year of age, with a corrected duodenal web. Pancreatic immunohistochemistry revealed a few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon, and somatostatin. Exocrine histology was variable. Mitchell et al. (2004) concluded that this combination of multiple congenital anomalies represented a distinct autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development.
Galan-Gomez et al. (2007) reported a girl with neonatal diabetes, acholia, and hyperbilirubinemia, born of consanguineous Spanish Gypsy parents. On laparotomy she was found to have type C duodenal atresia, hypoplastic pancreas, and intestinal malrotation; the gallbladder and extrahepatic biliary ducts were not observed, and technetium scintigraphy confirmed the absence of extrahepatic biliary ducts. She died at 60 days of age; the parents did not permit an autopsy.
Chappell et al. (2008) reported a Pakistani girl, born to first-cousin parents, who had neonatal diabetes, duodenal atresia, gallbladder agenesis, and an anteriorly placed anus. No pancreatic abnormality was found on abdominal ultrasound. In the first year of life, she underwent surgical repair of her intestinal anomalies, and at age 1 year her development was considered to be normal. Because their patient had neonatal diabetes without a demonstrable structural pancreatic abnormality, Chappell et al. (2008) concluded that a deficit in pancreatic function is involved. The authors noted that Mitchell et al. (2004) considered the phenotype of their cases to be distinct from that of the cases described by Martinez-Frias et al. (1992), Anneren et al. (1998), and Gentile and Fiorente (1999) (see 611346); however, Chappell et al. (2008) reviewed all of those reports and suggested that they represent the same syndrome, comprised of 6 key features: neonatal diabetes mellitus, intestinal atresia, malrotation, biliary atresia, gallbladder hypoplasia, and absent or abnormal pancreas.
Martinovici et al. (2010) reported a male infant, born of first-cousin parents, who had severe intrauterine growth retardation (IUGR), congenital hemochromatosis, neonatal diabetes, and duodenal atresia. There were no dysmorphic features. Laparotomy on day 2 of life confirmed duodenal atresia with apple peel-type jejunal atresia and intestinal malrotation as well as agenesis of the gallbladder; cholangiography was suggestive of biliary atresia, and liver biopsy confirmed severe siderosis of the hepatocytes without parenchymal loss or fibrosis. At 2 months of age, cholangio-MRI showed hypoplasia of the pancreas. Upon repeat laparotomy, cholangiography demonstrated cystic dilation of the extrahepatic bile ducts, with permeability of both biliary and pancreatic ducts, precluding surgical correction. The infant died shortly thereafter; autopsy was declined. Family history was remarkable for many cases of diabetes mellitus, including the mother, suggestive of monogenic diabetes; the father had impaired fasting glucose. Martinovici et al. (2010) noted that diabetes was reported in 1 of the consanguineous families with 2 affected children described by Mitchell et al. (2004).
Smith et al. (2010) reported 2 unrelated patients with IUGR and duodenal atresia: one was a male infant, born to nonconsanguineous French parents, in whom neonatal diabetes was diagnosed at day 2. His course was complicated by refractory ascites, sepsis, and gastrointestinal hemorrhage, from which he died at 2.5 months of age. Family history was relevant for gestational diabetes in the mother and type I diabetes in the father. The other patient was a female infant, born to nonconsanguineous Irish parents, who was diagnosed with neonatal diabetes requiring insulin treatment following surgery to repair her duodenal atresia.
Sansbury et al. (2015) studied a Turkish family in which 2 double first cousins had intestinal atresia consistent with a diagnosis of Mitchell-Riley syndrome, but did not develop diabetes until the ages of 3 years and 6 years. The first patient was a 9-year-old girl who was born at 32 weeks' gestation with duodenal atresia, jejunal web, and Meckel diverticulum. At age 2 years, hyperglycemia was noted but no further investigation or treatment was pursued. She presented at 3 years of age with diabetic ketoacidosis, which was then treated with daily insulin injections. Further evaluation at 5 years of age revealed absent gallbladder. She had an identical twin who was diagnosed with duodenal atresia but died of complication of prematurity and surgery at age 1 month. The second patient was her 9-year-old male cousin who was born at 34 weeks' gestation with duodenal atresia and mid-gut rotation. He was noted to have asymptomatic fasting hyperglycemia at age 5 years, at which time no treatment was initiated; he was diagnosed with diabetes after presenting with hyperglycemia at age 6 years, and treated with daily insulin. He also had chronic iron deficiency anemia of unknown etiology; he had no structural abnormality of the hepatobiliary tract, and liver function tests were always within normal limits. Family history included 4 relatives with adult-onset diabetes; all 4 were nonobese and treated with oral hypoglycemic agents.
Mapping
Smith et al. (2010) performed high-resolution homozygosity mapping in the proband with neonatal diabetes, duodenal and jejunal atresia, annular pancreas, and gallbladder agenesis from Pakistani 'family 1,' previously reported by Mitchell et al. (2004), and a Pakistani girl with neonatal diabetes, duodenal atresia, gallbladder agenesis, and an anteriorly placed anus, previously reported by Chappell et al. (2008). Smith et al. (2010) identified 3 homozygosity-by-descent regions that were common in the 2 probands, totaling 24 Mb. Among the genes in this region, only RFX6 (612659) on chromosome 6q21-q22 had pancreas-enriched expression in the TiGER database (Liu et al., 2008) and also showed increased expression in human pancreas concordant with the appearance of endocrine cells.
Inheritance
Mitchell-Riley syndrome is an autosomal recessive disorder (Smith et al., 2010).
Molecular Genetics
Smith et al. (2010) analyzed the candidate gene RFX6 and identified homozygosity or compound heterozygosity for RFX6 mutations in 5 of 6 probands with neonatal diabetes, hypoplastic or annular pancreas, intestinal atresia and/or malrotation, and gallbladder hypoplasia or agenesis, including splice site mutations in 2 patients previously reported by Mitchell et al. (2004) (612659.0001-612659.0003, respectively) and missense mutations in the 2 patients previously reported by Chappell et al. (2008) (S271P; 612659.0004) and Martinovici et al. (2010) (R181Q; 612659.0005), respectively, as well as an out-of-frame deletion in a new proband (612659.0006). No DNA was available from a sixth proband with neonatal diabetes and duodenal atresia, but analysis of the nonconsanguineous Irish parents revealed no mutation; similarly, no mutation was detected in the parents of the patient with Martinez-Frias syndrome (601346) previously described by Gentile and Fiorente (1999). Noting that some Martinez-Frias syndrome patients were reported to have esophageal atresia and hypospadias and none had neonatal diabetes, Smith et al. (2010) proposed that the apparently distinct phenotype of RFX6 mutation-positive patients be designated 'Mitchell-Riley syndrome.'
In 2 Turkish double first cousins, who had features consistent with Mitchell-Riley syndrome except for childhood-onset rather than neonatal diabetes, Sansbury et al. (2015) identified compound heterozygosity for 2 nonsense mutations in the RFX6 gene (R726X, 612659.0007; R866X, 612659.0008). The parents were each heterozygous for 1 of the mutations, each of which had been inherited from the respective grandmother. Noting that the 2 affected cousins exhibited a relatively milder phenotype than previously reported patients, including later onset of diabetes, no liver pathology apart from absent gallbladder in 1 patient, and a greater age of survival, Sansbury et al. (2015) suggested that their mutations might result in incomplete inactivation of RFX6.
### Exclusion Studies
Mitchell et al. (2004) performed genetic analysis of a Pakistani girl, born of consanguineous parents ('family 1'), who had neonatal diabetes, distal duodenal atresia and type IIIA jejunal atresia, annular pancreas, and absent gallbladder, but found no duplication or uniparental isodisomy of PLAGL1 (603044) on chromosome 6q24, no contiguous gene deletion involving the glucokinase gene (GCK; 138079), and no mutation in the coding sequences or splice sites of IPF1 (600733).
In a Pakistani girl, born of consanguineous parents, who had neonatal diabetes, duodenal atresia, absent gallbladder, and an anteriorly placed anus, Chappell et al. (2008) excluded methylation defects, duplication of 6q24, and parental isodisomy of chromosome 6. Sequencing of 7 genes with a recognized role in monogenic forms of diabetes as well as a novel candidate gene, HNF6 (604164), known to be involved in hepatobiliary and pancreatic development, did not reveal any mutations.
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation ABDOMEN Liver \- Cholestasis Pancreas \- Hypoplastic or annular pancreas \- Absence of insulin, glucagon, and somatostatin by pancreatic immunohistochemistry Biliary Tract \- Acholia \- Absent gallbladder \- Biliary atresia Gastrointestinal \- Duodenal atresia \- Jejunal atresia \- Intestinal malrotation \- Malabsorption \- Diarrhea \- Anteriorly placed anus (rare) ENDOCRINE FEATURES \- Neonatal diabetes \- Diabetes, childhood-onset (in some patients) LABORATORY ABNORMALITIES \- Hyperglycemia \- Low or undetectable insulin \- Low or undetectable C-peptide \- Hyperbilirubinemia MISCELLANEOUS \- Frequently fatal within the first year of life MOLECULAR BASIS \- Caused by mutation in the regulatory factor X, 6 gene (RFX6, 612659.0001 ) ▲ 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
|
MITCHELL-RILEY SYNDROME
|
c2748662
| 7,508 |
omim
|
https://www.omim.org/entry/615710
| 2019-09-22T15:51:17 |
{"mesh": ["C567570"], "omim": ["615710"], "orphanet": ["293864"], "synonyms": ["Alternative titles", "DIABETES, NEONATAL, WITH PANCREATIC HYPOPLASIA, INTESTINAL ATRESIA, AND GALLBLADDER APLASIA OR HYPOPLASIA"]}
|
A number sign (#) is used with this entry because variation in several different genes, including the human leukocyte antigens (e.g., HLA-DR; see 142860), likely influences the response to the hepatitis B vaccine.
Description
More than 2 billion people have been infected with the hepatitis B virus (HBV; see 610424), and more than 350 million of these people are chronic carriers. Each year more than half a million die as a result of acute or chronic HBV infection. Vaccination has been highly successful at preventing new HBV infections and has been implemented into the national immunization programs of more than 150 countries. However, the immune response to HBV vaccination varies greatly among individuals, with 5 to 10% of healthy adults failing to produce protective levels of antibodies. Several factors have been implicated in determining the response to HBV vaccination, including physical factors, such as age, gender, obesity, immunosuppression, and smoking, as well as variation in genes of the immune system (summary by Davila et al., 2010).
Molecular Genetics
Alper et al. (1989) followed up on a previous observation of a bimodal antibody response to hepatitis B vaccine, with about 14% of individuals being low responders. It had been found that the low responders included a greater-than-expected number of homozygotes for the MHC haplotype HLA-B8,SC01,DR3. In the follow-up study of 5 homozygotes and 9 heterozygotes for this haplotype, Alper et al. (1989) found a striking difference in antibody response between the 2 groups. Nepom (1989) pointed out that there are several possible mechanisms for observations such as this. A primary role of HLA class II products is to bind antigenic peptides. The resulting complex is a key signal for activation of T lymphocytes through the T-cell receptor. Immunologic unresponsiveness may also be involved in the pathogenesis of some complex infectious disorders, such as schistosomiasis (see 181460) and leprosy (see 609888), in which persons who are genetically 'high responders' may have immune-mediated sequelae marked by inflammatory, fibrotic, or granulomatous changes, whereas those with a poor response or none at all have a different clinical course. Similarly, HLA-associated differences in susceptibility to autoimmune diseases may be regulated by the same sort of mechanism, e.g., type I diabetes (see 222100) and rheumatoid arthritis (180300).
Davila et al. (2010) used a 2-stage investigation to study genetic variation in 914 immune candidate genes in 1,646 Indonesians who received HBV vaccine. They identified 6 SNPs within the HLA region, rs3817963, rs5000563, rs2395177, rs7192, rs6928482, and rs6906021, that were associated, after correction for multiple comparisons, with failure to produce protective levels of antibodies after vaccination. An additional SNP, rs6789153, located in the 3-prime downstream region of FOXP1 (605515), was also significantly associated with failure to produce protective levels of antibodies. FOXP1 is a transcription factor involved in B-cell development. Davila et al. (2010) proposed that identification of additional non-HLA genes, which are likely to account for up to 50% of heritability of the response to HBV vaccine, could facilitate the design of more effective vaccines.
Immunology \- Bimodal antibody response to hepatitis B vaccine \- Low response associated with MHC haplotype HLA-B8,SC01,DR3 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
|
HEPATITIS B VACCINE, RESPONSE TO
|
c1840634
| 7,509 |
omim
|
https://www.omim.org/entry/142395
| 2019-09-22T16:40:21 |
{"omim": ["142395"], "synonyms": ["Alternative titles", "HBV VACCINE, RESPONSE TO"]}
|
Hypospadias
Other namespronounce = /haɪpoʊˈspeɪdiəs/[1][2]
Different types of hypospadias
SpecialtyUrology, medical genetics
Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location in the head of the penis. It is the second-most common birth abnormality of the male reproductive system, affecting about one of every 250 males at birth.[3] Roughly 90% of cases are the less serious distal hypospadias, in which the urethral opening (the meatus) is on or near the head of the penis (glans). The remainder have proximal hypospadias, in which the meatus is all the way back on the shaft of the penis, near or within the scrotum. Shiny tissue that should have made the urethra extends from the meatus to the tip of the glans; this tissue is called the urethral plate.
In most cases, the foreskin is less developed and does not wrap completely around the penis, leaving the underside of the glans uncovered. Also, a downward bending of the penis, commonly referred to as chordee, may occur.[4] Chordee is found in 10% of distal hypospadias[3] and 50% of proximal hypospadias[5] cases at the time of surgery. Also, the scrotum may be higher than usual on either side of the penis (called penoscrotal transposition).
The cause of hypospadias is unknown. It most often occurs by itself, without other variations, although in about 10% of cases it may be part of an intersex condition or a medical syndrome with multiple abnormalities.[6][7]
The most common associated difference is an undescended testicle, which has been reported in around 3% of infants with distal hypospadias and 10% with proximal hypospadias.[8] The combination of hypospadias and an undescended testicle sometimes indicates a child has an intersex condition, so additional testing may be recommended to make sure the child does not have congenital adrenal hyperplasia with salt wasting or a similar condition where immediate medical intervention is needed.[9][10] Otherwise no blood tests or X-rays are routinely needed in newborns with hypospadias.[3]
Hypospadias can be a symptom or indication of an intersex condition, but the presence of hypospadias alone is not enough to classify a person as intersex. In most cases, hypospadias is not associated with any other condition.[11]
## Contents
* 1 Presentation
* 1.1 Complications
* 2 Diagnosis
* 3 Treatment
* 3.1 Age at surgery
* 3.2 Preoperative hormones
* 3.3 Surgery
* 4 Outcomes
* 5 Epidemiology
* 6 Adults
* 7 Notable indiviuals with hypospadias
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Presentation[edit]
### Complications[edit]
There is noted to be an increase in erectile problems in people with hypospadias, particularly when associated with a chordee (down curving of the shaft). There is usually minimal interaction with ability to ejaculate in hypospadias providing the meatus remains distal. This can also be affected by the coexistence of posterior urethral valves. There is an increase in difficulties associated with ejaculation however including increased rate of pain on ejaculation and weak/dribbling ejaculation. The rates of these problems are the same regardless of whether or not the hypospadias is surgically corrected. [12]
## Diagnosis[edit]
A penis with hypospadias usually has a characteristic appearance. Not only is the meatus (urinary opening) lower than usual, but the foreskin is also often only partially developed, lacking the usual amount that would cover the glans on the underside, causing the glans to have a hooded appearance. However, newborns with partial foreskin development do not necessarily have hypospadias, as some have a meatus in the usual place with a hooded foreskin, called “chordee without hypospadias”.
In other cases, the foreskin (prepuce) is typical and the hypospadias is concealed. This is called "megameatus with intact prepuce". The condition is discovered during newborn circumcision or later in childhood when the foreskin begins to retract. A newborn with typical-appearing foreskin and a straight penis who is discovered to have hypospadias after the start of circumcision can have circumcision completed without concern for jeopardizing hypospadias repair.[13][14] Hypospadias is almost never discovered after a circumcision.[citation needed]
## Treatment[edit]
Where hypospadias is seen as a genital ambiguity in a child, the World Health Organization standard of care is to delay surgery until the child is old enough to participate in informed consent, unless emergency surgery is needed because the child lacks a urinary opening. Hypospadias is not a serious medical condition. A urinary opening that is not surrounded by glans tissue is more likely to “spray” the urine, which can cause a man to sit to urinate because he cannot reliably stand and hit the toilet. Chordee is a separate condition, but where it occurs, the downward curvature of the penis may be enough to make sexual penetration more difficult. For these reasons or others, people with hypospadias may choose to seek urethroplasty, a surgical extension of the urethra using a skin graft.
Surgery can extend the urinary channel to the end of the penis, straighten bending, and/or change the foreskin (by either circumcision or by altering its appearance to look more typical (“prepucioplasty”), depending on the desire of the patient. Urethroplasty failure rates vary enormously, from around 5% for the simplest repairs to damage in a normal urethra by an experienced surgeon, to 15-20% when a buccal graft from the inside of the mouth can be used to extend a urethra, to close to 50% when graft urethral tubes are constructed from other skin.[15]
When the hypospadias is extensive--third degree/penoscrotal--or has associated differences in sex development such as chordee or cryptorchidism, the best management can be a more complicated decision. The world standard (UN and WHO) forbids nonessential surgery to produce a "normal" appearance without the informed consent of the patient,[16] and the American Academy of Pediatrics currently recommends but does not require the same standard. The AAP Textbook of Pediatric Care states "Gender assignment in patients with genital ambiguity should be made only after careful investigation by a multidisciplinary team; increasingly, surgical decisions are delayed until the child is able to participate in the decision-making process." [17] A karyotype and endocrine evaluation should be performed to detect intersex conditions or hormone deficiencies that have major health risks (i.e. salt-wasting). If the penis is small, testosterone or human chorionic gonadotropin (hCG) injections may be given with consent to enlarge it before surgery if this will increase the chance of a successful urethral repair.[3]
Surgical repair of severe hypospadias may require multiple procedures and mucosal grafting. Preputial skin is often used for grafting and circumcision should be avoided before repair. In patients with severe hypospadias, surgery often produces unsatisfactory results, such as scarring, curvature, or formation of urethral fistulas, diverticula, or strictures. A fistula is an unwanted opening through the skin along the course of the urethra, and can result in urinary leakage or an abnormal stream. A diverticulum is an "outpocketing" of the lining of the urethra which interferes with urinary flow and may result in posturination leakage. A stricture is a narrowing of the urethra severe enough to obstruct flow. Reduced complication rates even for third-degree repair (e.g., fistula rates below 5%) have been reported in recent years from centers with the most experience.[18] However, typical complications in urethroplasty for severe hypospadias can lead to long surgical cycles of failure and repair, and side effects may include loss of sexual or urinary function.[19] Research suggests failure rates are higher when urethroplasty corrects a born condition rather than disease or injury[20] so patients and families considering surgery for hypospadias should have realistic expectations about the risks and benefits.[21]
### Age at surgery[edit]
The results of surgery are probably not influenced by the age at which repair is done.[22][23] Teens and adults typically spend one night in the hospital after surgery.
### Preoperative hormones[edit]
Hormones potentially increase the size of the penis, and have been used in children with proximal hypospadias who have a smaller penis. Numerous articles report testosterone injections or topical creams increase the length and circumference of the penis. However, few studies discuss the impact of this treatment on the success of corrective surgery, with conflicting results.[23][24] Therefore, the role, if any, for preoperative hormone stimulation is not clear at this time.
### Surgery[edit]
Hypospadias repair is done under general anesthesia, most often supplemented by a nerve block to the penis or a caudal block to reduce the general anesthesia needed, and to minimize discomfort after surgery.
Many techniques have been used during the past 100 years to extend the urinary channel to the desired location. Today, the most common operation, known as the tubularized incised plate or “TIP” repair, rolls the urethral plate from the low meatus to the end of the glans. TIP repair, also called the Snodgrass Repair (after the creator of the method, Dr. Warren Snodgrass), is the most widely-used procedure and surgical method for hypospadias repair worldwide. This procedure can be used for all distal hypospadias repairs, with complications afterwards expected in less than 10% of cases.[25][26]
Less consensus exists regarding proximal hypospadias repair.[27] TIP repair can be used when the penis is straight or has mild downward curvature, with success in 85%.[25] Alternatively, the urinary channel can be reconstructed using the foreskin, with reported success in from 55% to 75%.[28]
Most distal and many proximal hypospadias are corrected in a single operation. However, those with the most severe condition having a urinary opening in the scrotum and downward bending of the penis are often corrected in a two-stage operation. During the first operation the curvature is straightened. At the second, the urinary channel is completed. Any complications may require additional interventions for repair.
* Example of penis with hypospadias
* Penis with hypospadias (1) and two fistulae (2)
## Outcomes[edit]
Most non-intersex children having hypospadias repair heal without complications. This is especially true for distal hypospadias operations, which are successful in over 90% of cases.
Problems that can arise include a small hole in the urinary channel below the meatus, called a fistula. The head of the penis, which is open at birth in children with hypospadias and is closed around the urinary channel at surgery, sometimes reopens, known as glans dehiscence. The new urinary opening can scar, resulting in meatal stenosis, or internal scarring can create a stricture, either of which cause partial blockage to urinating. If the new urinary channel balloons when urinating a child is diagnosed with a diverticulum.
Most complications are discovered within six months after surgery, although they occasionally are not found for many years. In general, when no problems are apparent after repair in childhood, new complications arising after puberty are uncommon. However, some problems that were not adequately repaired in childhood may become more pronounced when the penis grows at puberty, such as residual penile curvature or urine spraying due to rupture of the repair at the head of the penis.
Complications are usually corrected with another operation, most often delayed for at least six months after the last surgery to allow the tissues to heal sufficiently before attempting another repair. Results when circumcision or foreskin reconstruction are done are the same.[29][30] (Figure 4a, 4b)
Patients and surgeons had differing opinions as to outcomes of hypospadias repair, that is, patients might not be satisfied with a cosmetic result considered satisfactory by the surgeon, but patients with a cosmetic result considered not very satisfactory by the surgeon may themselves be satisfied. Overall, patients were less satisfied than surgeons.[12]
## Epidemiology[edit]
Hypospadias is among the most common birth defects in the world and is said to be the second-most common birth defect in the male reproductive system, occurring once in every 250 males.[31]
Due to variations in the reporting requirements of different national databases, data from such registries cannot be used to accurately determine either incidence of hypospadias or geographical variations in its occurrences.[3]
## Adults[edit]
While most hypospadias repairs are done in childhood, occasionally, an adult desires surgery because of urinary spraying or unhappiness with the appearance. Other adults wanting surgery have long-term complications as a result of childhood surgeries.
A direct comparison of surgical results in children versus adults found they had the same outcomes, and adults can undergo hypospadias repair or reoperations with good expectations for success.[23]
## Notable indiviuals with hypospadias[edit]
* Tiger Devore[32][33]
* Gabriel J. Martín[34][35]
* Scout Schultz[36]
## See also[edit]
* Pediatric urology
* Andrology
* Cryptorchidism
* Bladder exstrophy, cloacal exstrophy
* Perineal urethra, pseudovaginal perineoscrotal hypospadias
* Ambiguous genitalia, intersex, intersex surgery
* Androgen insensitivity syndrome
* Testicular dysgenesis syndrome
## References[edit]
1. ^ Entry "hypospadias" in Merriam-Webster Online Dictionary.
2. ^ OED 2nd edition, 1989 as /hɪpəʊˈspeɪdɪəs/~/haɪpəʊˈspeɪdɪəs/
3. ^ a b c d e Snodgrass W (2012). "Chapter 130: Hypospadias". In Wein A, Campbell MF, Walsh PC (eds.). Campbell-Walsh Urology, Tenth Edition. Elsevier. pp. 3503–3536. ISBN 978-1-4160-6911-9.
4. ^ King S, Beasley S (2012) [1st. Pub. 1986]. "Chapter 9.1:Surgical Conditions in Older Children". In South M (ed.). Practical Paediatrics, Seventh Edition. Churchill Livingstone, Elsevier. pp. 266–267. ISBN 978-0-702-04292-8.
5. ^ Snodgrass W, Prieto J (October 2009). "Straightening ventral curvature while preserving the urethral plate in proximal hypospadias repair". The Journal of Urology. 182 (4 Suppl): 1720–5. doi:10.1016/j.juro.2009.02.084. PMID 19692004.
6. ^ Stoll C, Alembik Y, Roth MP, Dott B (September 1990). "Genetic and environmental factors in hypospadias". Journal of Medical Genetics. 27 (9): 559–63. doi:10.1136/jmg.27.9.559. PMC 1017217. PMID 2231648.
7. ^ Calzolari E, Contiero MR, Roncarati E, Mattiuz PL, Volpato S (August 1986). "Aetiological factors in hypospadias". Journal of Medical Genetics. 23 (4): 333–7. doi:10.1136/jmg.23.4.333. PMC 1049700. PMID 3746833.
8. ^ Wu H, Wei Z, M G (2002). "Hypospadias and enlarged prostatic utricle". Chinese Journal of Urology. 12: 51–3.
9. ^ Kaefer M, Tobin MS, Hendren WH, Bauer SB, Peters CA, Atala A, et al. (April 1997). "Continent urinary diversion: the Children's Hospital experience". The Journal of Urology. 157 (4): 1394–9. doi:10.1016/S0022-5347(01)64998-X. PMID 9120962.
10. ^ Tarman GJ, Kaplan GW, Lerman SL, McAleer IM, Losasso BE (January 2002). "Lower genitourinary injury and pelvic fractures in pediatric patients". Urology. 59 (1): 123–6, discussion 126. doi:10.1016/S0090-4295(01)01526-6. PMID 11796295.
11. ^ Tidy, Colin (January 19, 2016). "Hypospadias". Patient. Patient Platform Ltd. Retrieved October 18, 2018.
12. ^ a b Mieusset R, Soulié M (2005). "Hypospadias: psychosocial, sexual, and reproductive consequences in adult life". Journal of Andrology. 26 (2): 163–8. doi:10.1002/j.1939-4640.2005.tb01078.x. PMID 15713818.
13. ^ Snodgrass WT, Khavari R (July 2006). "Prior circumcision does not complicate repair of hypospadias with an intact prepuce". The Journal of Urology. 176 (1): 296–8. doi:10.1016/S0022-5347(06)00564-7. PMID 16753427.
14. ^ Chalmers D, Wiedel CA, Siparsky GL, Campbell JB, Wilcox DT (May 2014). "Discovery of hypospadias during newborn circumcision should not preclude completion of the procedure". The Journal of Pediatrics. 164 (5): 1171–1174.e1. doi:10.1016/j.jpeds.2014.01.013. PMID 24534572.
15. ^ "Urethroplasty". Department of Urology. 2016-06-06. Retrieved 2019-06-14.
16. ^ "United Nations Fact Sheet-Intersex" (PDF).
17. ^ "Disorders of Sex Development | American Academy of Pediatrics Textbook of Pediatric Care, 2nd Edition | Pediatric Care Online | AAP Point-of-Care-Solutions". pediatriccare.solutions.aap.org. Retrieved 2019-06-14.
18. ^ "Re operation with Dr Nicol Bush & Dr Warren Snodgrass". PARC Urology Hypospadias Center. 2016-07-15. Retrieved 2019-05-09.
19. ^ Bayne, Aaron P.; Jones, Eric A. (2010). "Complications of hypospadias repair". In Taneja, Samir S. (ed.). Complications of Urologic Surgery (4th ed.). W.B. Saunders. pp. 713–722. ISBN 978-1-4160-4572-4.
20. ^ Suh JG, Choi WS, Paick JS, Kim SW (July 2013). "Surgical Outcome of Excision and End-to-End Anastomosis for Bulbar Urethral Stricture". Korean Journal of Urology. 54 (7): 442–7. doi:10.4111/kju.2013.54.7.442. PMC 3715707. PMID 23878686.
21. ^ "What are some of the risks of penile surgery?". ISSM. 2012-02-21. Retrieved 2019-06-14.
22. ^ Warren T. Snodgrass (2013-05-13). Pediatric Urology: Evidence for Optimal Patient Management. Springer Science & Business Media. pp. 117–. ISBN 978-1-4614-6910-0.
23. ^ a b c Bush N, Snodgrass W (August 2014). "Response to "Re: Snodgrass W, et al. Duration of follow-up to diagnose hypospadias urethroplasty complications. J Pediatr Urol 2014;10:783-784"". Journal of Pediatric Urology. 10 (4): 784–5. doi:10.1016/j.jpurol.2014.04.022. PMID 24999242.
24. ^ Kaplan GW (September 2008). "Does administration of transdermal dihydrotestosterone gel before hypospadias repair improve postoperative outcomes?". Nature Clinical Practice. Urology. 5 (9): 474–5. doi:10.1038/ncpuro1178. PMID 18679395. S2CID 22512786.
25. ^ a b Snodgrass WT, Bush N, Cost N (August 2010). "Tubularized incised plate hypospadias repair for distal hypospadias". Journal of Pediatric Urology. 6 (4): 408–13. doi:10.1016/j.jpurol.2009.09.010. PMID 19837000.
26. ^ Wilkinson DJ, Farrelly P, Kenny SE (June 2012). "Outcomes in distal hypospadias: a systematic review of the Mathieu and tubularized incised plate repairs". Journal of Pediatric Urology. 8 (3): 307–12. doi:10.1016/j.jpurol.2010.11.008. PMID 21159560.
27. ^ Castagnetti M, El-Ghoneimi A (October 2010). "Surgical management of primary severe hypospadias in children: systematic 20-year review". The Journal of Urology. 184 (4): 1469–74. doi:10.1016/j.juro.2010.06.044. PMID 20727541.
28. ^ Warren T. Snodgrass (2013-05-13). Pediatric Urology: Evidence for Optimal Patient Management. Springer Science & Business Media. pp. 129–. ISBN 978-1-4614-6910-0.
29. ^ Suoub M, Dave S, El-Hout Y, Braga LH, Farhat WA (October 2008). "Distal hypospadias repair with or without foreskin reconstruction: A single-surgeon experience". Journal of Pediatric Urology. 4 (5): 377–80. doi:10.1016/j.jpurol.2008.01.215. PMID 18790424.
30. ^ Snodgrass W, Dajusta D, Villanueva C, Bush N (August 2013). "Foreskin reconstruction does not increase urethroplasty or skin complications after distal TIP hypospadias repair". Journal of Pediatric Urology. 9 (4): 401–6. doi:10.1016/j.jpurol.2012.06.008. PMID 22854388.
31. ^ Gatti JM. "Epidemiology". Medscape Reference. Retrieved 22 January 2013.
32. ^ "Male or female? Babies born on the sliding sex scale". British Broadcasting Corporation. 11 October 2011. Retrieved 2016-05-12.
33. ^ Littlefield, Amy (August 13, 2018). "Intersex People Want to End Nonconsensual Surgeries. A California Resolution Is Their 'Warning Shot.'". Rewire.News. Retrieved 2018-11-30.
34. ^ Intersexualidad: «Nunca me sentí niña y mi comportamiento masculino era un problema». ABC. 20 October 2014.
35. ^ La barba me dio la razón: aunque me criaran como una niña, yo era un niño. El País. 30 June 2016.
36. ^ Lieberman, Hallie (August 29, 2018). "The Trigger Effect". The Atavist Magazine (82). Archived from the original on September 1, 2018. Retrieved 2018-08-31.
## Further reading[edit]
* Austin PF, Siow Y, Fallat ME, Cain MP, Rink RC, Casale AJ (October 2002). "The relationship between müllerian inhibiting substance and androgens in boys with hypospadias". The Journal of Urology. 168 (4 Pt 2): 1784–8, discussion 1788. doi:10.1016/S0022-5347(05)64413-8. PMID 12352359.
* Patel RP, Shukla AR, Snyder HM (October 2004). "The island tube and island onlay hypospadias repairs offer excellent long-term outcomes: a 14-year followup". The Journal of Urology. 172 (4 Pt 2): 1717–9, discussion 1719. doi:10.1097/01.ju.0000138903.20136.22. PMID 15371798.
* Retik AB, Atala A (May 2002). "Complications of hypospadias repair". The Urologic Clinics of North America. 29 (2): 329–39. doi:10.1016/S0094-0143(02)00026-5. PMID 12371224.
* Shukla AR, Patel RP, Canning DA (August 2004). "Hypospadias". The Urologic Clinics of North America. 31 (3): 445–60, viii. doi:10.1016/j.ucl.2004.04.020. PMID 15313054.
* International Trends in Rates of Hypospadias and Cryptorchidism
* Uretheral graft technique (Camillo Il Grande)
* "Special issue on hypospadias". Indian Journal of Urology. 24 (2). 2008.
## External links[edit]
Classification
D
* ICD-10: Q54
* ICD-9-CM: 752.61
* MeSH: D007021
* DiseasesDB: 29907
External resources
* MedlinePlus: 001286
* eMedicine: ped/1136
Wikimedia Commons has media related to Hypospadias.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypospadias
|
c0848558
| 7,510 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypospadias
| 2021-01-18T19:02:53 |
{"mesh": ["D007021"], "umls": ["C0848558"], "orphanet": ["440"], "wikidata": ["Q1132108"]}
|
This article is about medically-recognized chronic adrenal insufficiency. For a term used in alternative medicine, see Adrenal fatigue.
Adrenal insufficiency
Adrenal gland
SpecialtyEndocrinology
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention.[1][2] Craving for salt or salty foods due to the urinary losses of sodium is common.[3]
Addison's disease and congenital adrenal hyperplasia can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in abdominal pains, vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis).[4] An adrenal crisis may occur if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow.[4]
Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland does not make adequate amounts of the hormones that assist in regulating adrenal function.[1][5][6] This is called secondary or tertiary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus, respectively.[7]
## Contents
* 1 Types
* 2 Signs and symptoms
* 3 Causes
* 3.1 Corticosteroid withdrawal
* 3.2 Adrenal dysgenesis
* 3.3 Impaired steroidogenesis
* 3.4 Adrenal destruction
* 4 Pathophysiology
* 5 Diagnosis
* 5.1 Effects
* 6 Treatment
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Types[edit]
There are three major types of adrenal insufficiency.
* Primary adrenal insufficiency is due to impairment of the adrenal glands.
* 80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis.
* One subtype is called idiopathic, meaning of unknown cause.
* Other cases are due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.
* Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus.[8] Its principal causes include pituitary adenoma (which can suppress production of adrenocorticotropic hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced); and Sheehan's syndrome, which is associated with impairment of only the pituitary gland.
* Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone (CRH).[9] Causes can include brain tumors and sudden withdrawal from long-term exogenous steroid use (which is the most common cause overall).[10]
## Signs and symptoms[edit]
Signs and symptoms include: hypoglycemia, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present.[4] Eosinophilia may also occur.[11]
## Causes[edit]
Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse–Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency.[12] The latter is termed critical illness–related corticosteroid insufficiency.
For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addison's Disease), tuberculosis, AIDS, and metastatic disease.[12] Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.[12]
Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease).[13] Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.[14]
Adrenoleukodystrophy can also cause adrenal insufficiency.[15]
Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.[citation needed]
Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage).[16]
### Corticosteroid withdrawal[edit]
Use of high-dose steroids for more than a week begins to produce suppression of the person's adrenal glands because the exogenous glucocorticoids suppress release of hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the person is vulnerable to adrenal insufficiency during times of stress, such as illness, due to both adrenal atrophy and suppression of CRH and ACTH release.[17][18] Use of steroids joint injections may also result in adrenal suppression after discontinuation.[19]
### Adrenal dysgenesis[edit]
All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia due to DAX-1 gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.[16]
### Impaired steroidogenesis[edit]
To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia.[verification needed]
Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations.[16] Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin).[16]
### Adrenal destruction[edit]
Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialised world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992).[20] This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.[21]
Adrenal destruction is also a feature of adrenoleukodystrophy (ALD), and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.[22]
## Pathophysiology[edit]
Hyponatremia can be caused by glucocorticoid deficiency. Low levels of glucocorticoids leads to systemic hypotension (one of the effects of cortisol is to increase peripheral resistance), which results in a decrease in stretch of the arterial baroreceptors of the carotid sinus and the aortic arch. This removes the tonic vagal and glossopharyngeal inhibition on the central release of ADH: high levels of ADH will ensue, which will subsequently lead to increase in water retention and hyponatremia.[citation needed]
Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance (in fact a positive sodium balance may occur).[23]
## Diagnosis[edit]
The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids.[citation needed]
Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.[24]
If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison's Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.[citation needed]
### Effects[edit]
Source of pathology CRH ACTH DHEA DHEA-S cortisol aldosterone renin Na K Causes5
hypothalamus
(tertiary)1 low low low low low3 low low low low tumor of the hypothalamus (adenoma), antibodies, environment (i.e. toxins), head injury
pituitary
(secondary) high2 low low low low3 normal low low normal tumor of the pituitary (adenoma), antibodies, environment, head injury,
surgical removal6, Sheehan's syndrome
adrenal glands
(primary)7 high high high high low4 low high low high tumor of the adrenal (adenoma), stress, antibodies, environment, Addison's disease, trauma, surgical removal (resection), miliary tuberculosis of the adrenal
1 Automatically includes diagnosis of secondary (hypopituitarism)
2 Only if CRH production in the hypothalamus is intact
3 Value doubles or more in stimulation
4 Value less than doubles in stimulation
5 Most common, does not include all possible causes
6 Usually because of very large tumor (macroadenoma)
7 Includes Addison's disease
## Treatment[edit]
* ;Adrenal crisis
* Intravenous fluids[4]
* Intravenous steroid (Solu-Cortef/injectable hydrocortisone) later hydrocortisone, prednisone or methylpredisolone tablets[4]
* Rest
* ;Cortisol deficiency (primary and secondary)
* Hydrocortisone (Cortef)
* Prednisone (Deltasone)
* Prednisolone (Delta-Cortef)
* Methylprednisolone (Medrol)
* Dexamethasone (Decadron)
* Hydrocortisone granules in casules for opening (Alkindi)[25]
* ;Mineralocorticoid deficiency (low aldosterone)
* Fludrocortisone acetate
(To balance sodium, potassium and increase water retention)[4]
## See also[edit]
* Addison's disease – primary adrenocortical insufficiency
* Cushing's syndrome – overproduction of cortisol
* Insulin tolerance test – another test used to identify sub-types of adrenal insufficiency
* Adrenal fatigue (hypoadrenia) – a term used in alternative medicine to describe a believed exhaustion of the adrenal glands
## References[edit]
1. ^ a b Eileen K. Corrigan (2007). "Adrenal Insufficiency (Secondary Addison's or Addison's Disease)". NIH Publication No. 90-3054.
2. ^ Adrenal+Insufficiency at the US National Library of Medicine Medical Subject Headings (MeSH)
3. ^ Ten S, New M, Maclaren N (2001). "Clinical review 130: Addison's disease 2001". J. Clin. Endocrinol. Metab. 86 (7): 2909–22. doi:10.1210/jc.86.7.2909. PMID 11443143.
4. ^ a b c d e f Ashley B. Grossman, MD (2007). "Addison's Disease". Adrenal Gland Disorders.
5. ^ Brender E, Lynm C, Glass RM (2005). "JAMA patient page. Adrenal insufficiency". JAMA. 294 (19): 2528. doi:10.1001/jama.294.19.2528. PMID 16287965.
6. ^ "Dorlands Medical Dictionary:adrenal insufficiency".
7. ^ "Secondary Adrenal Insufficiency: Adrenal Disorders: Merck Manual Professional".
8. ^ "hypopituitary". WebMD. 2006.
9. ^ "Archived copy". Archived from the original on 2010-06-13. Retrieved 2010-03-31.CS1 maint: archived copy as title (link)
10. ^ "Causes of secondary and tertiary adrenal insufficiency in adults". Retrieved 10 November 2016.
11. ^ Montgomery ND, Dunphy CH, Mooberry M, Laramore A, Foster MC, Park SI, Fedoriw YD (2013). "Diagnostic complexities of eosinophilia". Archives of Pathology & Laboratory Medicine. 137 (2): 259–69. doi:10.5858/arpa.2011-0597-RA. PMID 23368869. S2CID 17918640.
12. ^ a b c Table 20-7 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
13. ^ Thomas A Wilson, MD (2007). "Adrenal Insufficiency". Adrenal Gland Disorders.
14. ^ Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. (2016). "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab (Practice Guideline. Review). 101 (2): 364–89. doi:10.1210/jc.2015-1710. PMC 4880116. PMID 26760044.
15. ^ Thomas A Wilson, MD (1999). "Adrenoleukodystrophy". Cite journal requires `|journal=` (help)
16. ^ a b c d Ten S, New M, Maclaren N (2001). "Clinical review 130: Addison's disease 2001". The Journal of Clinical Endocrinology and Metabolism. 86 (7): 2909–2922. doi:10.1210/jc.86.7.2909. PMID 11443143.
17. ^ Kaminstein, David S. William C. Shiel Jr. (ed.). "Steroid Drug Withdrawal". MedicineNet. Retrieved 10 April 2013.
18. ^ Dernis, E; Ruyssen-Witrand, A; Mouterde, G; Maillefert, JF; Tebib, J; Cantagrel, A; Claudepierre, P; Fautrel, B; Gaudin, P; Pham, T; Schaeverbeke, T; Wendling, D; Saraux, A; Loët, XL (October 2010). "Use of glucocorticoids in rheumatoid arthritis - practical modalities of glucocorticoid therapy: recommendations for clinical practice based on data from the literature and expert opinion". Joint, Bone, Spine : Revue du Rhumatisme. 77 (5): 451–7. doi:10.1016/j.jbspin.2009.12.010. PMID 20471886.
19. ^ Stitik, Todd P. (2010). Injection Procedures: Osteoarthritis and Related Conditions. Springer Science & Business Media. p. 47. ISBN 9780387765952.
20. ^ Winqvist O, Karlsson FA, Kämpe O (June 1992). "21-Hydroxylase, a major autoantigen in idiopathic Addison's disease". The Lancet. 339 (8809): 1559–62. doi:10.1016/0140-6736(92)91829-W. PMID 1351548.
21. ^ Husebye ES, Perheentupa J, Rautemaa R, Kämpe O (May 2009). "Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I". Journal of Internal Medicine. 265 (5): 514–29. doi:10.1111/j.1365-2796.2009.02090.x. PMID 19382991.
22. ^ Kennedy, Ron. "Addison's Disease". The Doctors' Medical Library. Archived from the original on 2013-04-12. Retrieved 2015-07-29.
23. ^ Schrier, R. W. (2006). "Body Water Homeostasis: Clinical Disorders of Urinary Dilution and Concentration". Journal of the American Society of Nephrology. 17 (7): 1820–32. doi:10.1681/ASN.2006030240. PMID 16738014.
24. ^ Addison Disease~workup at eMedicine
25. ^ "Alkindi Summary of Product Characteristics" (PDF).
## Further reading[edit]
* Bornstein, SR; Allolio, B; Arlt, W; Barthel, A; Don-Wauchope, A; Hammer, GD; Husebye, ES; Merke, DP; Murad, MH; Stratakis, CA; Torpy, DJ (February 2016). "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 101 (2): 364–89. doi:10.1210/jc.2015-1710. PMC 4880116. PMID 26760044.
## External links[edit]
Classification
D
* ICD-10: E27.1-E27.4
* ICD-9-CM: 255.4
* MeSH: D000309
External resources
* eMedicine: emerg/16
* v
* t
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Gonadotropin
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*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
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*[nM]: nanomolars
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|
Adrenal insufficiency
|
c0001623
| 7,511 |
wikipedia
|
https://en.wikipedia.org/wiki/Adrenal_insufficiency
| 2021-01-18T18:49:52 |
{"mesh": ["D000309"], "umls": ["C0001623"], "icd-9": ["255.4"], "icd-10": ["E27.1", "E27.4"], "wikidata": ["Q2507454"]}
|
Boomerang dysplasia
Other namesDwarfism with short, bowed, rigid limbs and characteristic facies
Boomerang dysplasia has an autosomal dominant pattern of inheritance.
SpecialtyMedical genetics
Boomerang dysplasia is a lethal form of osteochondrodysplasia[1] known for a characteristic congenital feature in which bones of the arms and legs are malformed into the shape of a boomerang.[2] Death usually occurs in early infancy due to complications arising from overwhelming systemic bone malformations.[1]
Osteochondrodysplasias are skeletal disorders that cause malformations of both bone and cartilage.
## Contents
* 1 Presentation
* 2 Cause
* 3 Genetics
* 4 Diagnosis
* 5 Treatment
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
Prenatal and neonatal diagnosis of boomerang dysplasia includes several prominent features found in other osteochondrodysplasias, though the "boomerang" malformation seen in the long bones is the delineating factor.[2]
Featured symptoms of boomerang dysplasia include: dwarfism[3] (a lethal type of infantile dwarfism caused by systemic bone deformities),[4] underossification (lack of bone formation) in the limbs, spine and ilium (pelvis);[1] proliferation of multinucleated giant-cell chondrocytes (cells that produce cartilage and play a role in skeletal development - chondrocytes of this type are rarely found in osteochondrodysplasias),[5] brachydactyly (shortened fingers) and micromelia (undersized, shortened bones).[2]
The characteristic "boomerang" malformation presents intermittently among random absences of long bones throughout the skeleton, in affected individuals.[3][6] For example, one individual may have an absent radius and fibula, with the "boomerang" formation found in both ulnas and tibias.[6] Another patient may present "boomerang" femora, and an absent tibia.[3]
## Cause[edit]
Mutations in the Filamin B (FLNB) gene cause boomerang dysplasia.[1] FLNB is a cytoplasmic protein that regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal development.[7] Disruptions in this pathway, caused by FLNB mutations, result in the bone and cartilage abnormalities associated with boomerang dysplasia.[citation needed]
Chondrocytes, which also have a role in bone development, are susceptible to these disruptions and either fail to undergo ossification, or ossify incorrectly.[1][7]
FLNB mutations are involved in a spectrum of lethal bone dysplasias. One such disorder, atelosteogenesis type I, is very similar to boomerang dysplasia, and several symptoms of both often overlap.[8][9]
## Genetics[edit]
Early journal reports of boomerang dysplasia suggested X-linked recessive inheritance, based on observation and family history.[3] It was later discovered, however, that the disorder is actually caused by a sporadic genetic mutation fitting an autosomal dominant genetic profile.[8]
Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.[10]
Boomerang dysplasia, although an autosomal dominant disorder,[8] is not inherited because those afflicted do not live beyond infancy.[1] They cannot pass the gene to the next generation.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (July 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (July 2017)
## See also[edit]
* Larsen syndrome
## References[edit]
1. ^ a b c d e f Bicknell LS, Morgan T, Bonife L, Wessels MW, Bialer MG, Willems PJ, Cohen DH, Krakow D, Robertson SP (2005). "Mutations in FLNB cause boomerang dysplasia". Am J Med Genet. 42 (7): e43. doi:10.1136/jmg.2004.029967. PMC 1736093. PMID 15994868.
2. ^ a b c Wessels MW, Den Hollander NS, Dekrijger RR, Bonife L, Superti-Furga A, Nikkels PG, Willems PJ (2003). "Prenatal diagnosis of boomerang dysplasia". Am J Med Genet A. 122 (2): 148–154. doi:10.1002/ajmg.a.20239. PMID 12955767. S2CID 42013969.
3. ^ a b c d Winship I, Cremin B, Beighton P (1990). "Boomerang dysplasia". Am J Med Genet. 36 (4): 440–443. doi:10.1002/ajmg.1320360413. PMID 2202214.
4. ^ Kozlowski K, Tsuruta T, Kameda Y, Kan A, Leslie G (1981). "New forms of neonatal death dwarfism. Report of 3 cases". Pediatr Radiol. 10 (3): 155–160. doi:10.1007/BF00975190. PMID 7194471. S2CID 31143908.
5. ^ Urioste M, Rodriguez JL, Bofarull J, Toran N, Ferrer C, Villa A (1997). "Giant-cell chondrocytes in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia". Am J Med Genet. 68 (3): 342–346. doi:10.1002/(SICI)1096-8628(19970131)68:3<342::AID-AJMG17>3.0.CO;2-T. PMID 9024569.
6. ^ a b Kozlowski K, Sillence D, Cortis-Jones R, Osborn R (1985). "Boomerang dysplasia". Br J Radiol. 58 (688): 369–371. doi:10.1259/0007-1285-58-688-369. PMID 4063680.
7. ^ a b Lu J, Lian G, Lenkinski R, De Grand A, Vaid RR, Bryce T, Stasenko M, Boskey A, Walsh C, Sheen V (2007). "Filamin B mutations cause chondrocyte defects in skeletal development". Hum Mol Genet. 16 (14): 1661–1675. doi:10.1093/hmg/ddm114. PMID 17510210.
8. ^ a b c Nishimura G, Horiuchi T, Kim OH, Sasamoto Y (1997). "Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome". Am J Med Genet. 73 (2): 132–138. doi:10.1002/(SICI)1096-8628(19971212)73:2<132::AID-AJMG6>3.0.CO;2-W. PMID 9409862.
9. ^ Greally MT, Jewett T, Smith WL Jr, Penick GD, Williamson RA (1993). "Lethal bone dysplasia in a fetus with manifestations of Atelosteogenesis type I and Boomerang dysplasia". Am J Med Genet. 47 (4): 1086–1091. doi:10.1002/ajmg.1320470731. PMID 8291529.
10. ^ "Boomerang dysplasia". Genetics Home Reference. 2016-02-22. Retrieved 2016-03-01.
## External links[edit]
Classification
D
* ICD-10: Q68.5
* ICD-9-CM: 754.44
* OMIM: 112310
* MeSH: C536573
* SNOMED CT: 254054000
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* Limb-girdle muscular dystrophy 1B
* Charcot–Marie–Tooth disease 2B1
* LMNB
* Barraquer–Simons syndrome
* LEMD3
* Buschke–Ollendorff syndrome
* Osteopoikilosis
* LBR
* Pelger–Huet anomaly
* Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
Microtubules
Kinesin
* Charcot–Marie–Tooth disease 2A
* Hereditary spastic paraplegia 10
Dynein
* Primary ciliary dyskinesia
* Short rib-polydactyly syndrome 3
* Asphyxiating thoracic dysplasia 3
Other
* Tauopathy
* Cavernous venous malformation
Membrane
* Spectrin: Spinocerebellar ataxia 5
* Hereditary spherocytosis 2, 3
* Hereditary elliptocytosis 2, 3
Ankyrin: Long QT syndrome 4
* Hereditary spherocytosis 1
Catenin
* APC
* Gardner's syndrome
* Familial adenomatous polyposis
* plakoglobin (Naxos syndrome)
* GAN (Giant axonal neuropathy)
Other
* desmoplakin: Striate palmoplantar keratoderma 2
* Carvajal syndrome
* Arrhythmogenic right ventricular dysplasia 8
* plectin: Epidermolysis bullosa simplex with muscular dystrophy
* Epidermolysis bullosa simplex of Ogna
* plakophilin: Skin fragility syndrome
* Arrhythmogenic right ventricular dysplasia 9
* centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)
Related topics: Cytoskeletal proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Boomerang dysplasia
|
c0432201
| 7,512 |
wikipedia
|
https://en.wikipedia.org/wiki/Boomerang_dysplasia
| 2021-01-18T18:35:43 |
{"gard": ["933"], "mesh": ["C536573"], "umls": ["C0432201"], "icd-9": ["754.44"], "icd-10": ["Q68.5"], "orphanet": ["1263"], "wikidata": ["Q4943512"]}
|
Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is a rare form of diffuse large B-cell lymphoma occurring most commonly in patients over the age of 50 (usually between 70-75 years of age), without overt immunodeficiency, and presenting with nodal and extranodal involvement (in sites such as the stomach, lung, skin and pancreas) and B symptoms (fever, night sweats, weight loss). The tumor is characterized by an aggressive course and a short survival rate.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly
|
None
| 7,513 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289661
| 2021-01-23T19:02:18 |
{"icd-10": ["C83.3"], "synonyms": ["EBV-positive DLBCL of the elderly"]}
|
Supernumerary root
SpecialtyDentistry
Supernumerary roots is a condition found in teeth when there may be a larger number of roots than expected. The most common teeth affected are mandibular (lower) canines, premolars, and molars, especially third molars. Canines and most premolars, except for maxillary (upper) first premolars, usually have one root. Maxillary first premolars and mandibular molars usually have two roots. Maxillary molars usually have three roots. When an extra root is found on any of these teeth, the root is described as a supernumerary root.[1] The clinical significance of this condition is associated with dentistry when accurate information regarding root canal anatomy is required when root canal treatment is required.[2]
## References[edit]
1. ^ Olga A.C.Ibsen, Joan Andersen Phelan . Oral Pathology for the Dental Hygienist - Pageburst E-Book on Kno6: Oral Pathology for the Dental Hygienist - Pageburst E-Book on Kno. Elsevier Health Sciences. pp. 170–. ISBN 978-1-4557-7511-8.
2. ^ Ahmed, HMA (2012). "Accessory roots in maxillary molar teeth: a review and endodontic considerations". Australian Dental Journal. 57: 123. Retrieved 30 June 2020.
## External links[edit]
Classification
D
* ICD-10: K00.2
* ICD-9-CM: 520.2
* v
* t
* e
Developmental tooth disease/tooth abnormality
Quantity
* Anodontia/Hypodontia
* Hyperdontia
Shape and size
* Concrescence
* Fusion
* Gemination
* Dens evaginatus/Talon cusp
* Dens invaginatus
* Enamel pearl
* Macrodontia
* Microdontia
* Taurodontism
* Supernumerary roots
Formation
* Dilaceration
* Regional odontodysplasia
* Turner's hypoplasia
* Enamel hypoplasia
* Ectopic enamel
Other hereditary
* Amelogenesis imperfecta
* Dentinogenesis imperfecta
* Dentin dysplasia
* Regional odontodysplasia
Other
* Dental fluorosis
* Tooth impaction
This dentistry 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
|
Supernumerary root
|
c0266038
| 7,514 |
wikipedia
|
https://en.wikipedia.org/wiki/Supernumerary_root
| 2021-01-18T19:06:55 |
{"umls": ["C0266038"], "icd-9": ["520.2"], "icd-10": ["K00.2"], "wikidata": ["Q7644076"]}
|
Paroxysmal nocturnal dyspnoea
SpecialtyPulmonology
Paroxysmal nocturnal dyspnea or paroxysmal nocturnal dyspnoea (PND) is an attack of severe shortness of breath and coughing that generally occurs at night.[1] It usually awakens the person from sleep, and may be quite frightening.[2] Though simple orthopnea may be relieved by sitting upright at the side of the bed with legs dangling,[3] in those with PND, coughing and wheezing often persist in this position.
## Contents
* 1 Mechanisms
* 2 Diagnosis
* 3 Treatment
* 4 References
## Mechanisms[edit]
PND is caused in part by the depression of the respiratory center during sleep,[4] which may reduce arterial oxygen tension, particularly in patients with interstitial lung disease and reduced pulmonary compliance.
Similar to orthopnea, in the horizontal position there is redistribution of blood volume from the lower extremities to the lungs. In normal individuals this has little effect on lungs, but in patients in whom the additional volume cannot be pumped out by the left ventricle due to left ventricular weakness, there is a significant reduction in lung capacity which results in shortness of breath. Additionally, in patients with congestive heart failure the pulmonary circulation may already be overloaded because of the failing left ventricle. When a person lies down, the left ventricle is unable to match the output of a more normally functioning right ventricle on increased venous return to the lungs; causing pulmonary congestion. Pulmonary congestion decreases when the patient assumes a more erect position, and this is accompanied by an improvement in symptoms.[4]
## Diagnosis[edit]
Evaluation should begin with a detailed cardiac history and physical exam; echocardiography and CXR may be used though the diagnostic workup varies depending on the suspected cause.[citation needed]
## Treatment[edit]
Treatment for paroxysmal nocturnal dyspnea depends on the underlying cause. Options often include oxygen, diuretics, heart medications, antihypertensives, and bronchodilators to reverse wheezing.[citation needed]
## References[edit]
1. ^ Charles Pollak; Michael J. Thorpy; Jan Yager (2009). The Encyclopedia of Sleep and Sleep Disorders. Infobase Publishing. pp. 170–. ISBN 978-1-4381-2577-0. Retrieved 16 December 2012.
2. ^ Lippincott Williams & Wilkins (1 March 2007). Nursing: Interpreting signs & symptoms. Lippincott Williams & Wilkins. pp. 469–. ISBN 978-1-58255-668-0. Retrieved 16 December 2012.
3. ^ Allen R. Myers (2005). NMS Medicine, 5e. Lippincott Williams & Wilkins. pp. 3–tttg. ISBN 978-0-7817-5468-2. Retrieved 16 December 2012.
4. ^ a b Mukerji, bVaskar (1990). "Dyspnea, Orthopnea, and Paroxysmal Nocturnal Dyspnea". In Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.). Clinical Methods: The; History, Physical, and Laboratory Examinations (3r uy5u5u5u5d ed.). Butterworths. ISBN 0-407-02853-6. Retrieved 2009-03-14.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Paroxysmal nocturnal dyspnoea
|
c0013405
| 7,515 |
wikipedia
|
https://en.wikipedia.org/wiki/Paroxysmal_nocturnal_dyspnoea
| 2021-01-18T18:56:44 |
{"mesh": ["D004418"], "icd-9": ["428.1"], "icd-10": ["E50.1"], "wikidata": ["Q3229220"]}
|
Human mental dissociative disorder
Depersonalization-derealization disorder
Illustration of depersonalization or a detachment from self
SpecialtyPsychiatry, clinical psychology
SymptomsDepersonalization, Derealization
Usual onsetYoung adulthood[1]
Durationchronic, episodic
TreatmentPsychotherapy
Frequency1–2% (general population)[2]
Depersonalization-derealization disorder (DPDR, DPD)[3][4] is a mental disorder in which the person has persistent or recurrent feelings of depersonalization or derealization. Depersonalization is described as feeling disconnected or detached from one's self. Individuals may report feeling as if they are an outside observer of their own thoughts or body, and often report feeling a loss of control over their thoughts or actions.[5] Derealization is described as detachment from one's surroundings. Individuals experiencing derealization may report perceiving the world around them as foggy, dreamlike/surreal, or visually distorted.[5]
Depersonalization-derealization disorder is thought to be caused largely by interpersonal trauma such as childhood abuse [6] Adverse early childhood experiences, specifically emotional abuse and neglect have been linked to the development of depersonalization symptoms.[7] Triggers may include significant stress, panic attacks, and drug use.[6]
Diagnostic criteria for depersonalization-derealization disorder includes persistent or recurrent feelings of detachment from one's mental or bodily processes or from one's surroundings.[8] A diagnosis is made when the dissociation is persistent and interferes with the social or occupational functions of daily life.[3]
While depersonalization-derealization disorder was once considered rare, lifetime experiences with it occur in about 1–2% of the general population.[9] The chronic form of the disorder has a reported prevalence of 0.8 to 1.9%.[10][11] While brief episodes of depersonalization or derealization can be common in the general population, the disorder is only diagnosed when these symptoms cause substantial distress or impair social, occupational, or other important areas of functioning.[12]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Psychosocial
* 2.2 Neurobiology
* 3 Diagnosis
* 3.1 Assessment
* 3.2 Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
* 3.3 International Classification of Diseases 11th Revision (ICD-11)
* 3.4 Differential Diagnoses
* 3.4.1 Neurologic
* 3.4.2 Psychiatric
* 3.4.3 Intoxication/Withdrawal from Illicit Substances
* 4 Prevention
* 5 Treatment
* 5.1 Cognitive behavioral therapy
* 5.2 Medications
* 5.3 Repetitive Transcranial Magnetic Stimulation (rTMS)
* 6 Prognosis
* 7 Epidemiology
* 7.1 Relation to other psychiatric disorders
* 8 History
* 9 Society and culture
* 10 See also
* 11 References
* 12 External links
## Signs and symptoms[edit]
The core symptoms of depersonalization-derealization disorder is the subjective experience of "unreality in one's self",[13] or detachment from one's surroundings. People who are diagnosed with depersonalization also often experience an urge to question and think critically about the nature of reality and existence.[12]
Individuals with depersonalization describe feeling disconnected from their physicality; feeling as if they are not completely occupying their own body; feeling as if their speech or physical movements are out of their control; feeling detached from their own thoughts or emotions; and experiencing themselves and their lives from a distance.[14] While depersonalization involves detachment from one's self, individuals with derealization feel detached from their surroundings, as if the world around them is foggy, dreamlike, or visually distorted. Individuals with the disorder commonly describe a feeling as though time is passing them by and they are not in the notion of the present. In some cases, individuals may be unable to accept their reflection as their own, or they may have out-of-body experiences.[14] One-third to one-half of patients with DPDR also experience hearing internal voices.[15] This is to differentiate from external voices which are more commonly found in psychoses. Additionally some individuals experience difficulty concentrating and problems with memory retrieval. These individuals sometimes lack the "feeling" of a memory where they are able to recall a memory but feel as if they did not personally experience it.[16][17] These experiences which strike at the core of a person's identity and consciousness may cause a person to feel uneasy or anxious.[12] The inner turmoil created by the disorder can also result in depression.[18]
First experiences with depersonalization may be frightening, with patients fearing loss of control, dissociation from the rest of society and functional impairment.[11] The majority of people with depersonalization-derealization disorder misinterpret the symptoms, thinking that they are signs of serious psychosis or brain dysfunction. This commonly leads to an increase of anxiety and obsession, which contributes to the worsening of symptoms.[19]
Factors that tend to diminish symptoms are comforting personal interactions, intense physical or emotional stimulation, and relaxation.[20] Distracting oneself (by engaging in conversation or watching a movie, for example) may also provide temporary relief. Some other factors that are identified as relieving symptom severity are diet or exercise, while alcohol and fatigue are listed by some as worsening their symptoms.[21]
Occasional, brief moments of mild depersonalization can be experienced by many members of the general population;[22] however, depersonalization-derealization disorder occurs when these feelings are strong, severe, persistent, or recurrent and when these feelings interfere with daily functioning.[18] DPDR episodes tend to be transient but duration is highly variable with some lasting as long as several weeks.[23][24]
## Causes[edit]
The exact cause of depersonalization is unknown, although biopsychosocial correlations and triggers have been identified. It has been thought that depersonalization can be caused by a biological response to dangerous or life-threatening situations which causes heightened senses and emotional numbing.[11]
### Psychosocial[edit]
There is growing evidence linking physical and sexual abuse in childhood with the development of dissociative disorders.[23] Childhood interpersonal trauma – emotional abuse in particular – is a significant predictor of a diagnosis of DPDR.[25] Compared to other types of childhood trauma, emotional abuse has been found to be the most significant predictor both of a diagnosis of depersonalization disorder and of depersonalization scores, but not of general dissociation scores.[26] Some studies suggest that greater emotional abuse and lower physical abuse predict depersonalization in adult women with PTSD.[27] Patients with high interpersonal abuse histories (HIA) show significantly higher scores on the Cambridge Depersonalization Scale, when compared to a control group.[28][7] Earlier age of abuse, increased duration and parental abuse tend to correlate with severity of dissociative symptoms.[23][29] Besides traumatic experiences, other common precipitators of the disorder include severe stress, major depressive disorder, panic attacks, and psychoactive substances.[30] People who live in highly individualistic cultures may be more vulnerable to depersonalization, due to threat hypersensitivity and an external locus of control.[31]
### Neurobiology[edit]
Animated image showing prefrontal cortex which is thought to play a role in DPDR
There is converging evidence that the prefrontal cortex may inhibit neural circuits that normally form the basis of emotional experience.[32] In an fMRI study of DPD patients, emotionally aversive scenes activated the right ventral prefrontal cortex. Participants demonstrated a reduced neural response in emotion-sensitive regions, as well as an increased response in regions associated with emotional regulation.[33] In a similar test of emotional memory, depersonalization disorder patients did not process emotionally salient material in the same way as did healthy controls.[34] In a test of skin conductance responses to unpleasant stimuli, the subjects showed a selective inhibitory mechanism on emotional processing.[35]
Studies are beginning to show that the temporoparietal junction has a role in multisensory integration, embodiment, and self-other distinction.[36] Several studies analyzing brain MRI findings from DPDR patients found decreased cortical thickness in the right middle temporal gyrus, reduction in grey matter volume in the right caudate, thalamus, and occipital gyri, as well as lower white matter integrity in the left temporal and right temporoparietal regions. However, no structural changes in the amygdala were observed.[37][38][39]
A PET scan found functional abnormalities in the visual, auditory, and somatosensory cortex, as well as in areas responsible for an integrated body schema.[40]
One study examining EEG readings found frontal alpha wave overactivation and increased theta activity waves in the temporal region of the left hemisphere.[41]
Image showing temporoparietal junction, a portion of the brain also thought to play a role in DPDR
It is unclear whether genetics plays a role; however, there are many neurochemical and hormonal changes in individuals with depersonalization disorder.[6] DPDR may be associated with dysregulation of the hypothalamic-pituitary-adrenal axis, the area of the brain involved in the "fight-or-flight" response. Patients demonstrate abnormal cortisol levels and basal activity. Studies found that patients with DPD could be distinguished from patients with clinical depression and posttraumatic stress disorder.[42][43]
The vestibular system may also play a role in DPDR. The vestibular system helps control balance, spatial orientation, motor coordination, but also plays a role in self-awareness. Disruption to this system can potentially cause a feeling of detachment from surroundings. Several studies have shown that patients with peripheral vestibular disease are also more likely to have dissociative symptoms when compared to healthy individuals.[44]
Dissociative symptoms are sometimes described by those with neurological diseases, such as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), etc., that directly affect brain tissue.[45]
## Diagnosis[edit]
### Assessment[edit]
Diagnosis is based on the self-reported experiences of the person followed by a clinical assessment. Psychiatric assessment includes a psychiatric history and some form of mental status examination. Since some medical and psychiatric conditions mimic the symptoms of DPD, clinicians must differentiate between and rule out the following to establish a precise diagnosis: temporal lobe epilepsy, panic disorder, acute stress disorder, schizophrenia, migraine, drug use, brain tumor or lesion.[14] No laboratory test for depersonalization-derealization disorder currently exists.[8] As patients with dissociative disorders likely experienced intense trauma in the past, concomitant dissociative disorders should be considered in patients diagnosed with a stress disorder (i.e. PTSD or acute stress disorder) [46]
The diagnosis of depersonalization disorder can be made with the use of the following interviews and scales:
* The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) is widely used, especially in research settings. This interview takes about 30 minutes to 1.5 hours, depending on individual's experiences.[47]
* The Dissociative Experiences Scale (DES) is a simple, quick, self-administered questionnaire that has been widely used to measure dissociative symptoms.[48] It has been used in hundreds of dissociative studies, and can detect depersonalization and derealization experiences.[49]
* The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview which makes DSM-IV diagnoses of somatization disorder, borderline personality disorder and major depressive disorder, as well as all the dissociative disorders.[50] It inquires about positive symptoms of schizophrenia, secondary features of dissociative identity disorder, extrasensory experiences, substance abuse and other items relevant to the dissociative disorders. The DDIS can usually be administered in 30–45 minutes.[50]
* The Cambridge Depersonalization Scale (CDS) is a method for determining the severity of depersonalization disorder. It has been proven and accepted as a valid tool for the diagnosis of depersonalization disorder in a clinical setting. It is also used in a clinical setting to differentiate minor episodes of depersonalization from actual symptoms of the disorder. Due to the success of the CDS, a group of Japanese researchers underwent the effort to translate the CDS into the J-CDS or the Japanese Cambridge Depersonalization Scale. Through clinical trials, the Japanese research team successfully tested their scale and determined its accuracy. One limitation is that the scale does not allow for the differentiation between past and present episodes of depersonalization. It should also be noted that it may be difficult for the individual to describe the duration of a depersonalization episode, and thus the scale may lack accuracy. The project was conducted in the hope that it would stimulate further scientific investigations into depersonalization disorder.[51]
### Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)[edit]
In the DSM-5, the word "derealization" was added to "depersonalization disorder" and renamed "depersonalization/derealization disorder" ("DPDR").[3] It remains classified as a dissociative disorder.[3]
Patients must meet the following criteria to be diagnosed per the DSM-5:[3]
1. Presence of persistent/recurrent episodes of depersonalization/derealization
2. Ability to distinguish between reality and dissociation during an episode (i.e. patient is aware of a perceptual disturbance)
3. Symptoms are severe enough to interfere with social, occupational, or other areas of functioning
4. Symptoms are not due to a substance or medication
5. Symptoms are not due to another psychiatric disorder
### International Classification of Diseases 11th Revision (ICD-11)[edit]
The ICD-11 has relisted DPDR as a disorder rather than a syndrome as previously, and has also reclassed it as a dissociative disorder from its previous listing as a neurotic disorder.[4] The description used in the ICD-11 is similar to the criteria found in the DSM-5. Individuals with DPDR are described as having persistent/recurrent symptoms of depersonalization/derealization, have intact reality testing, and symptoms are not better explained by another psychiatric/neural disorder, substance, medication, or head trauma. Symptoms are severe enough to cause distress or impairment in functioning.[52]
### Differential Diagnoses[edit]
DPDR differentials include neurologic and psychiatric conditions as well as side effects from illicit substances or medications.[9][53]
#### Neurologic[edit]
* Seizures
* Brain tumor
* Post-concussion syndrome
* Metabolic abnormalities
* Migraines
* Vertigo
* Meniere's disease
#### Psychiatric[edit]
* Panic attack
* Phobias
* PTSD
* Acute stress syndrome
* Depression
* Schizophrenia
* Borderline personality disorder
* Other dissociative disorders
#### Intoxication/Withdrawal from Illicit Substances[edit]
* Marijuana
* Hallucinogens
* MDMA
* Ketamine
## Prevention[edit]
Depersonalization-derealization disorder may be prevented by connecting children who have been abused with professional mental health help.[54] Some trauma specialists suggest increasing inquiry into information about children's trauma history and exposure to violence, since the majority of people (about 80%) responsible for child maltreatment are children's own parents.[55] Trauma-specific intervention for children may be a useful in preventing future symptoms.[56]
## Treatment[edit]
Treatment of DPDR is often difficult and refractory. Some clinicians speculate that this could be due to a delay in diagnosis by which point symptoms tend to be constant and less responsive to treatment.[9] Additionally, symptoms tend to overlap with other diagnoses.[44] Some results have been promising, but hard to evaluate with confidence due to the small size of trials.[57] However, recognizing and diagnosing the condition may in itself have therapeutic benefits, considering many patients express their problems as baffling and unique to them, but are in fact: one, recognized and described by psychiatry; and two, those affected by it are not the only individuals to be affected from the condition.[58] However, symptoms are often transient and can remit on their own without treatment.[23]
Treatment is primarily non-pharmacological and can include paradoxical intention, record keeping, positive reward, flooding, psychotherapy, cognitive-behavioral therapy, psychoeducation, self-hypnosis, and meditation.[59] Meditation with the focus on the body has been used to achieve self awareness as it allows feelings, which otherwise are put aside or neutralized by the DPD condition. Self-hypnosis training can be helpful and entails training patients to induce dissociative symptoms and respond in an alternative manner.[60] Psychoeducation involves counseling regarding the disorder, reassurance, and emphasis on DPDR as a perceptual disturbance rather than a true physical experience.[9] Clinical pharmacotherapy research continues to explore a number of possible options, including selective serotonin reuptake inhibitors, benzodiazepines, stimulants and opioid antagonists (ex: naltrexone).[9]
### Cognitive behavioral therapy[edit]
An open study of cognitive behavioral therapy has aimed to help patients reinterpret their symptoms in a nonthreatening way, leading to an improvement on several standardized measures.[61] A standardized treatment for DPD based on cognitive behavioral principles was published in the Netherlands in 2011.[62]
### Medications[edit]
Neither antidepressants nor antipsychotics have been found to be useful,[63] additionally, antipsychotics can worsen symptoms of depersonalisation.[32] Tentative evidence supports naloxone and naltrexone,[63] as well as gabapentin.[64]
A combination of an SSRI and a benzodiazepine has been proposed to be useful for DPD patients with anxiety.[65]
Modafinil used alone has been reported to be effective in a subgroup of individuals with depersonalization disorder (those who have attentional impairments, under-arousal and hypersomnia). However, clinical trials have not been conducted.[66]
### Repetitive Transcranial Magnetic Stimulation (rTMS)[edit]
Some studies have found repetitive transcranial magnetic stimulation (rTMS) to be helpful.[67][68][69] One study examined 12 patients with DPD that were treated with right temporoparietal junction (TPJ) rTMS and found that 50% showed improvement after three weeks of treatment. Five of the participants received an additional three weeks of treatment and reported overall a 68% improvement in their symptoms.[67] Treating patients with rTMS specifically at the TPJ may be an alternative treatment.[67]
## Prognosis[edit]
DPDR is typically chronic and continuous though some individuals report experiencing periods of remission. Exacerbations can be caused by psychologically stressful situations.[24] Michal et al. (2016) analyzed 2 case series on patients with DPDR and agreed that the condition tended to be chronic.[70]
## Epidemiology[edit]
Men and women are diagnosed in equal numbers with depersonalization disorder.[21] A 1991 study on a sample from Winnipeg, Manitoba estimated the prevalence of depersonalization disorder at 2.4% of the population.[71] A 2008 review of several studies estimated the prevalence between 0.8% and 1.9%.[65] This disorder is episodic in about one-third of individuals,[21] with each episode lasting from hours to months at a time. Depersonalization can begin episodically, and later become continuous at constant or varying intensity.[21]
Onset is typically during the teenage years or early 20s, although some report being depersonalized as long as they can remember, and others report a later onset.[20][21] The onset can be acute or insidious. With acute onset, some individuals remember the exact time and place of their first experience of depersonalization. This may follow a prolonged period of severe stress, a traumatic event, an episode of another mental illness, or drug use.[21] Insidious onset may reach back as far as can be remembered, or it may begin with smaller episodes of lesser severity that become gradually stronger. Patients with drug-induced depersonalization do not appear to be a clinically separate group from those with a non-drug precipitant.[72]
### Relation to other psychiatric disorders[edit]
Depersonalization exists as both a primary and secondary phenomenon, although making a clinical distinction appears easy, it is not absolute. The most common comorbid disorders are depression and anxiety, although cases of depersonalization disorder without symptoms of either do exist. Comorbid obsessive and compulsive behaviours may exist as attempts to deal with depersonalization, such as checking whether symptoms have changed and avoiding behavioural and cognitive factors that exacerbate symptoms. Many people with personality disorders such as schizoid personality disorder, schizotypal personality disorder, and borderline personality disorder will have high chances of having depersonalization disorder.
## History[edit]
The word depersonalization itself was first used by Henri Frédéric Amiel in The Journal Intime. The 8 July 1880 entry reads:
> I find myself regarding existence as though from beyond the tomb, from another world; all is strange to me; I am, as it were, outside my own body and individuality; I am depersonalized, detached, cut adrift. Is this madness?[73]
Depersonalization was first used as a clinical term by Ludovic Douglas in 1898 to refer to "a state in which there is the feeling or sensation that thoughts and acts elude the self and become strange; there is an alienation of personality – in other words a depersonalization". This description refers to personalization as a psychical synthesis of attribution of states to the self.[74]
Early theories of the cause of depersonalization focused on sensory impairment. Maurice Krishaber proposed depersonalization was the result of pathological changes to the body's sensory modalities which lead to experiences of "self-strangeness" and the description of one patient who "feels that he is no longer himself". One of Carl Wernicke's students suggested all sensations were composed of a sensory component and a related muscular sensation that came from the movement itself and served to guide the sensory apparatus to the stimulus. In depersonalized patients, these two components were not synchronized, and the myogenic sensation failed to reach consciousness. The sensory hypothesis was challenged by others who suggested that patient complaints were being taken too literally and that some descriptions were metaphors – attempts to describe experiences that are difficult to articulate in words. Pierre Janet approached the theory by pointing out his patients with clear sensory pathology did not complain of symptoms of unreality, and that those who have depersonalization were normal from a sensory viewpoint.[74]
Psychodynamic theory formed the basis for the conceptualization of dissociation as a defense mechanism. Within this framework, depersonalization is understood as a defense against a variety of negative feelings, conflicts, or experiences. Sigmund Freud himself experienced fleeting derealization when visiting the Acropolis in person; having read about it for years and knowing it existed, seeing the real thing was overwhelming and proved difficult for him to perceive it as real.[75] Freudian theory is the basis for the description of depersonalization as a dissociative reaction, placed within the category of psychoneurotic disorders, in the first two editions of the Diagnostic and Statistical Manual of Mental Disorders.[76]
Some argue that because depersonalization and derealization are both impairments to one's ability to perceive reality, they are merely two facets of the same disorder. Depersonalization also differs from delusion in the sense that the patient is able to differentiate between reality and the symptoms they may experience. The ability to sense that something is unreal is maintained when experiencing symptoms of the disorder. The problem with properly defining depersonalization also lies within the understanding of what reality actually is. In order to comprehend the nature of reality we must incorporate all the subjective experiences throughout and thus the problem of obtaining an objective definition is brought about again.[77]
## Society and culture[edit]
Depersonalization disorder has appeared in a variety of media. The director of the autobiographical documentary Tarnation, Jonathan Caouette, had depersonalization disorder. The screenwriter for the 2007 film Numb had depersonalization disorder, as does the film's protagonist played by Matthew Perry. Norwegian painter Edvard Munch's famous masterpiece The Scream may have been inspired by depersonalization disorder.[78] In Glen Hirshberg's novel The Snowman's Children, main female plot characters throughout the book had a condition that is revealed to be depersonalization disorder.[79] Suzanne Segal had an episode in her 20s that was diagnosed by several psychologists as depersonalization disorder, though Segal herself interpreted it through the lens of Buddhism as a spiritual experience, commonly known as "Satori" or "Samadhi".[80] The song "Is Happiness Just a Word?" by hip hop artist Vinnie Paz describes his struggle with depersonalization disorder. Adam Duritz, of the band Counting Crows, has often spoken about his diagnosis of depersonalization disorder.[81]
## See also[edit]
* Anosognosia
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55. ^ Kolk, Bessel A. van der (15 August 2017). "Developmental Trauma Disorder: Toward a rational diagnosis for children with complex trauma histories". Psychiatric Annals. 35 (5): 401–408. doi:10.3928/00485713-20050501-06. ISSN 0048-5713.
56. ^ Huppertz, Bernd (16 October 2018). Approaches to Psychic Trauma: Theory and Practice. Rowman & Littlefield. ISBN 978-1-4422-5815-0.
57. ^ Hunter, Elaine C. M.; Charlton, Jane; David, Anthony S. (2017). "Depersonalisation and derealisation: assessment and management". BMJ. 356: j745. doi:10.1136/bmj.j745. PMID 28336554. S2CID 206917634.
58. ^ Medford N, Sierra M, Baker D, David AS (2005). "Understanding and treating depersonalization disorder". Advances in Psychiatric Treatment. 11 (5): 92–100. doi:10.1192/apt.11.2.92.
59. ^ Maldonado, J; Spiegel, D (2002). A Guide to Treatments that Work, 2nd Edition. Oxford University Press. pp. 463–496.
60. ^ Spiegel, Herbert; Spiegel, David (2004). Trance and treatment : clinical uses of hypnosis (2nd ed.). Washington, DC: American Psychiatric Publishers. ISBN 1-58562-190-0. OCLC 54001039.
61. ^ Hunter EC, Baker D, Phillips ML, Sierra M, David AS (September 2005). "Cognitive-behaviour therapy for depersonalisation disorder: an open study". Behav Res Ther. 43 (9): 1121–30. doi:10.1016/j.brat.2004.08.003. PMID 16005701.
62. ^ Bar, E., & Minnen van, A. (2011). Protocollaire behandeling van de depersonalisatiestoornis. In: G.P.J. Keijsers, A.van Minnen, & C.A.L. Hoogduin (red.). Protocollaire behandelingen voor volwassenen met psychische klachten. Arnhem, Boom Cure & Care publishers.
63. ^ a b Sierra, M (January 2008). "Depersonalization disorder: pharmacological approaches". Expert Review of Neurotherapeutics. 8 (1): 19–26. doi:10.1586/14737175.8.1.19. PMID 18088198. S2CID 22180718.
64. ^ Perez, David L.; Matin, Nassim; Williams, Benjamin; Tanev, Kaloyan; Makris, Nikos; LaFrance, W. Curt; Dickerson, Bradford C. (January 2018). "Cortical Thickness Alterations Linked to Somatoform and Psychological Dissociation in Functional Neurological Disorders". Human Brain Mapping. 39 (1): 428–439. doi:10.1002/hbm.23853. ISSN 1065-9471. PMC 5747307. PMID 29080235.
65. ^ a b Sierra M (2008). "Depersonalization disorder: pharmacological approaches". Expert Rev Neurother. 8 (1): 19–26. doi:10.1586/14737175.8.1.19. PMID 18088198. S2CID 22180718.
66. ^ Mauricio Sierra (13 August 2009). Depersonalization: A New Look at a Neglected Syndrome. Cambridge, UK: Cambridge University Press. p. 120. ISBN 978-0-521-87498-4.
67. ^ a b c Mantovani, Antonio; Simeon, Daphne; Urban, Nina; Bulow, Peter; Allart, Anouk; Lisanby, Sarah (30 March 2011). "Temporo-parietal junction stimulation in the treatment of depersonalization disorder". Psychiatry Research. 186 (1): 138–140. doi:10.1016/j.psychres.2010.08.022. ISSN 0165-1781. PMID 20837362. S2CID 43658129.
68. ^ Christopeit, Marie; Simeon, Daphne; Urban, Nina; Gowatsky, Jaimie; Lisanby, Sarah H.; Mantovani, Antonio (January 2014). "Effects of repetitive transcranial magnetic stimulation (rTMS) on specific symptom clusters in depersonalization disorder (DPD)". Brain Stimulation. 7 (1): 141–143. doi:10.1016/j.brs.2013.07.006. ISSN 1876-4754. PMID 23941986. S2CID 27003955.
69. ^ Rachid, Fady (March 2017). "Treatment of a Patient With Depersonalization Disorder With Low Frequency Repetitive Transcranial Magnetic Stimulation of the Right Temporo-Parietal Junction in a Private Practice Setting". Journal of Psychiatric Practice. 23 (2): 145–147. doi:10.1097/PRA.0000000000000214. ISSN 1538-1145. PMID 28291041.
70. ^ Michal, Matthias; Adler, Julia; Wiltink, Jörg; Reiner, Iris; Tschan, Regine; Wölfling, Klaus; Weimert, Sabine; Tuin, Inka; Subic-Wrana, Claudia; Beutel, Manfred E.; Zwerenz, Rüdiger (December 2016). "A case series of 223 patients with depersonalization-derealization syndrome". BMC Psychiatry. 16 (1): 203. doi:10.1186/s12888-016-0908-4. ISSN 1471-244X. PMC 4924239. PMID 27349226.
71. ^ Ross CA (1991). "Epidemiology of multiple personality disorder and dissociation". Psychiatric Clinics of North America. 14 (3): 503–17. doi:10.1016/S0193-953X(18)30286-7. PMID 1946021.
72. ^ Medford N, Baker D, Hunter E, et al. (December 2003). "Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases". Addiction. 98 (12): 1731–6. doi:10.1111/j.1360-0443.2003.00548.x. PMID 14651505.
73. ^ Henri Frédéric Amiel's The Journal Intime Retrieved June 2, 2007
74. ^ a b Berrios GE, Sierra M (June 1997). "Depersonalization: a conceptual history". Hist Psychiatry. 8 (30 Pt 2): 213–29. doi:10.1177/0957154X9700803002. PMID 11619439. S2CID 45671151.
75. ^ Mayer-Gross W. (1935). "On depersonalization." British Journal of Medicine and Psychology (15)103–126.
76. ^ Simeon and Abugel p. 12 & 58
77. ^ Sogomy, Varga (June 2012). "Depersonalization and the Sense of Realness". Philosophy, Psychiatry, & Psychology. 19 (2).
78. ^ Simeon, D; Abugel J (2006). "The Blow of the Void: Depersonalization in Literature and Philosophy". Feeling unreal: depersonalization disorder and the loss of the self. United States: Oxford University Press. pp. 127–58. ISBN 978-0-19-517022-1.
79. ^ Hirshberg, Glen (2003). The Snowman's Children: A Novel. New York, NY: Carroll & Graf. ISBN 978-0-7867-1253-3.
80. ^ Suzanne Segal (1996). Collision With the Infinite: A Life Beyond the Personal Self. Blue Dove Press. ISBN 978-1-884997-27-3.
81. ^ "A Lesson in Humility from Adam Duritz". Men's Health. 30 September 2014. Archived from the original on 22 April 2016. Retrieved 30 May 2016.
## External links[edit]
* Depersonalization at Curlie
Classification
D
* ICD-10: F48.1
* ICD-9-CM: 300.6
* MeSH: D003861
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
* Paraphilia
* Fetishism
* Voyeurism
* Sexual maturation disorder
* Sexual relationship disorder
Other
* Factitious disorder
* Munchausen syndrome
* Intermittent explosive disorder
* Dermatillomania
* Kleptomania
* Pyromania
* Trichotillomania
* Personality disorder
Childhood and learning
Emotional and behavioral
* ADHD
* Conduct disorder
* ODD
* Emotional and behavioral disorders
* Separation anxiety disorder
* Movement disorders
* Stereotypic
* Social functioning
* DAD
* RAD
* Selective mutism
* Speech
* Stuttering
* Cluttering
* Tic disorder
* Tourette syndrome
Intellectual disability
* X-linked intellectual disability
* Lujan–Fryns syndrome
Psychological development
(developmental disabilities)
* Pervasive
* Specific
Mood (affective)
* Bipolar
* Bipolar I
* Bipolar II
* Bipolar NOS
* Cyclothymia
* Depression
* Atypical depression
* Dysthymia
* Major depressive disorder
* Melancholic depression
* Seasonal affective disorder
* Mania
Neurological and symptomatic
Autism spectrum
* Autism
* Asperger syndrome
* High-functioning autism
* PDD-NOS
* Savant syndrome
Dementia
* AIDS dementia complex
* Alzheimer's disease
* Creutzfeldt–Jakob disease
* Frontotemporal dementia
* Huntington's disease
* Mild cognitive impairment
* Parkinson's disease
* Pick's disease
* Sundowning
* Vascular dementia
* Wandering
Other
* Delirium
* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Depersonalization-derealization disorder
|
c0683416
| 7,516 |
wikipedia
|
https://en.wikipedia.org/wiki/Depersonalization-derealization_disorder
| 2021-01-18T19:00:17 |
{"gard": ["6260"], "mesh": ["D003861"], "umls": ["C0683416"], "icd-10": ["F48.1"], "wikidata": ["Q2338307"]}
|
A number sign (#) is used with this entry because of evidence that multisystemic smooth muscle dysfunction syndrome (MSMDS) is caused by heterozygous mutation in the ACTA2 gene (102620) on chromosome 10q23.
See also familial thoracic aortic aneurysm (AAT6; 611788), which can also be caused by ACTA2 mutation.
Clinical Features
Milewicz et al. (2010) described 7 unrelated patients ranging in age from 11 to 27 years who had clinical findings suggestive of vascular disease, consistent with previous ACTA2 mutations. However, there was higher penetrance and earlier onset of vascular disease and additional multisystem smooth muscle dysfunction was manifest. Three of these patients had previously been described by Khan et al. (2004), Lemire et al. (2004), and Ades et al. (1999), respectively. All patients shared the features of congenital mydriasis or fixed dilated pupils, as well as patent ductus arteriosus requiring repair in infancy. The patient previously reported by Lemire et al. (2004) had aortic coarctation that was repaired at age 4 months. All patients subsequently developed fusiform ascending aortic aneurysms extending to the arch during childhood, and 5 of 7 required surgical repair at age 10 to 25 years. The patient previously reported by Ades et al. (1999) had a dissection at 14 years of age. In addition to the aortic disease, all patients had cerebral vascular abnormalities including fusiform dilatation of the intimal carotid artery from the cavernous to the clinoidal segments, and the terminal region of the internal carotid arteries showed mild to moderate tapering indicative of stenosis of the artery and consistent with changes observed in Moyamoya disease (see 252350). Two of the patients, one reported by Milewicz et al. (2010) and one reported by Khan et al. (2004), underwent neurosurgical bypass for revascularization for Moyamoya disease. All 5 patients for whom imaging was reported had bilateral periventricular white matter hyperintensities, and 1 had changes consistent with a middle and anterior cerebral artery stroke. One patient had colpocephaly with a thin corpus callosum and somewhat small cerebral vermis and was diagnosed with developmental delay. In addition to the vascular abnormality, additional evidence of smooth muscle dysfunction included congenital mydriasis, hypotonic bladder, malrotation, and hyperperistalsis of the gastrointestinal tract. Two patients had malrotation. One patient had gallstones that spontaneously resolved and subsequently presented with hydrops of the gallbladder without evidence of residual gallstones. Biopsies of the esophagus, stomach, and small intestine revealed normal ganglionic cells and no specific neural or smooth muscle pathology. Four of the 5 patients for whom data were available had tachypnea at birth. One patient had hyperinflation of the upper lung segment, a hypoplastic lower lung segment, and a dilated pulmonary trunk at 14 years of age. The patient previously reported by Lemire et al. (2004) had evidence of cystic lung disease as an infant with biopsies showing alveolar dysgenesis consistent with developmental defect. One patient was diagnosed with primary pulmonary hypertension and underwent bilateral lung transplantation at age 18 months. The lung pathology showed pulmonary arterial hypertensive changes with smooth muscle cell hyperplasia and neointimal fibrocellular proliferative lesions. In addition, 2 out of 3 males had unilateral undescended testes. Two of the patients had asthma, and several patients had microaneurysms. One patient had microaneurysms of the retina, and one had a right ophthalmic artery occlusion.
Molecular Genetics
In 7 unrelated patients of northern European descent with multisystemic smooth muscle dysfunction syndrome, Milewicz et al. (2010) identified heterozygosity for a de novo R179H mutation in the ACTA2 gene (102620.0004).
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Mydriasis, congenital \- Small vessel retinal infarcts and aneurysms CARDIOVASCULAR Vascular \- Patent ductus arteriosus \- Thoracic aortic aneurysm \- Dilated pulmonary arteries \- Bilateral stenoses of the terminal internal carotid artery \- Small vessel brain infarcts and aneurysms \- Small vessel retinal infarcts and aneurysms \- Pulmonary hypertension RESPIRATORY \- Tachypnea Lung \- Lung disease, non-specific ABDOMEN Gastrointestinal \- Malrotation \- Hyperperistalsis GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism Bladder \- Hypotonic bladder NEUROLOGIC Central Nervous System \- Periventricular white matter hyperintensities, bilateral MISCELLANEOUS \- All de novo mutations \- Seven patients reported (as of March 2011) MOLECULAR BASIS \- Caused by mutation in the actin, alpha-2, smooth muscle, aorta gene (ACTA2, 102620.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MULTISYSTEMIC SMOOTH MUSCLE DYSFUNCTION SYNDROME
|
c3151201
| 7,517 |
omim
|
https://www.omim.org/entry/613834
| 2019-09-22T15:57:17 |
{"omim": ["613834"], "orphanet": ["404463"], "synonyms": ["Alternative titles", "MYDRIASIS, CONGENITAL, WITH PATENT DUCTUS ARTERIOSUS, THORACIC AORTIC ANEURYSM, AND VASCULOPATHY"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-27 (SCAR27) is caused by homozygous or compound heterozygous mutation in the GDAP2 gene (618128) on chromosome 1p12.
Description
Autosomal recessive spinocerebellar ataxia-27 (SCAR27) is an adult-onset neurologic disorder characterized by gait difficulties and other cerebellar signs, such as eye movement abnormalities, dysarthria, and difficulty writing. The disorder is progressive, and some patients may lose independent ambulation. Additional features include spasticity of the lower limbs and cognitive impairment. Brain imaging shows cerebellar atrophy (summary by Eidhof et al., 2018).
Clinical Features
Eidhof et al. (2018) reported 2 unrelated woman of European descent with onset of slowly progressive spinocerebellar ataxia in their thirties. Features included gait difficulties with frequent falls, dysarthria, difficulty writing, variable gaze-evoked nystagmus, jerky pursuits, and hypermetric saccades. They also had pyramidal signs, including spastic ataxic gait, lower limb hypertonia, and hyperreflexia; 1 patient had torticollis. At age 46, patient NIJ had normal cognition with some suggestion of mental slowing, but was able to walk with a spastic ataxic gait and had no autonomic disturbances. Patient AW had a more severe disease course. She had progressive cognitive decline and behavioral changes in her fifties, as well as clear progression of spasticity resulting in loss of ambulation at age 58. She lost speech and the ability to swallow, and was bedridden and mute at age 62, when she died of infectious complications. Brain imaging showed mild cerebellar atrophy in patient NIJ, and severe cerebellar and cortical atrophy in patient AW. Neuropathologic examination of patient AW showed cerebelloolivary atrophy with severe and diffuse loss of Purkinje cells, as well as astrocytic gliosis. Neuronal loss and gliosis were also observed in other brain regions, including the thalamus and some regions of the brainstem. Immunohistochemical studies showed some cytoplasmic ubiquitin- and p62 (SQSTM1; 601530)-positive inclusions, as well as neurofibrillary tangles, but no Lewy bodies or amyloid deposits were observed.
Inheritance
The transmission pattern of SCAR27 in the families reported by Eidhof et al. (2018) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 unrelated patients with SCAR27, Eidhof et al. (2018) identified homozygous or compound heterozygous loss-of-function mutations in the GDAP2 gene (618128.0001-618128.0003). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed, but all 3 variants were predicted to result in a loss of function.
Animal Model
Eidhof et al. (2018) found that knockdown of the Gdap2 gene in Drosophila decreased the lifespan of mutant flies and caused abnormal motor behavior, including righting defects, uncoordinated walking, and poor wing movement with droopy wings. Mutant flies were also more susceptible to oxidative stress and nutrient deprivation compared to controls, suggesting that Gdap2 may act as a stress-responsive gene.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Jerky pursuit \- Hypermetric saccades Neck \- Torticollis ABDOMEN Gastrointestinal \- Dysphagia MUSCLE, SOFT TISSUES \- Hypertonia of the lower limbs NEUROLOGIC Central Nervous System \- Spinocerebellar ataxia \- Gait ataxia \- Frequent falls \- Spasticity \- Hyperreflexia \- Dysarthria \- Cognitive decline \- Cerebellar atrophy \- Cerebral atrophy \- Loss of Purkinje cells in the cerebellum \- Gliosis Behavioral Psychiatric Manifestations \- Behavioral abnormalities \- Executive dysfunction \- Depression MISCELLANEOUS \- Adult onset \- Slowly progressive \- Two unrelated patients have been reported (last curated March 2019) MOLECULAR BASIS \- Caused by mutation in the ganglioside-induced differentiation-associated protein 2 gene (GDAP2, 618128.0001 ) ▲ 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
|
SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 27
|
None
| 7,518 |
omim
|
https://www.omim.org/entry/618369
| 2019-09-22T15:42:25 |
{"omim": ["618369"]}
|
A rare infectious disease of the nervous system caused by the bacterium Streptococcus pneumoniae, which is commonly part of the bacterial flora colonizing the nasopharyngeal mucosa. The disease is clinically characterized by typical symptoms of acute leptomeningitis, like fever, headache, neck stiffness, vomiting, and clouding of consciousness. It is frequently fatal and, in surviving patients, often accompanied by long-term sequelae, especially focal neurological deficits, hearing loss, cognitive impairment, and epilepsy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pneumococcal meningitis
|
c0025295
| 7,519 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=55655
| 2021-01-23T17:05:08 |
{"mesh": ["D008586"], "umls": ["C0025295"], "icd-10": ["G00.1"]}
|
A rare lysosomal disease characterized by intermittent vomiting, hypotonia, lethargy, opisthotonos, and fatal outcome in early infancy, associated with deficient acid phosphatase in lysosomes. There have been no further descriptions in the literature since 1971.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Lysosomal acid phosphatase deficiency
|
c0268410
| 7,520 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35121
| 2021-01-23T17:24:06 |
{"mesh": ["C562645"], "omim": ["200950"], "umls": ["C0268410"], "icd-10": ["E83.3"]}
|
Not to be confused with Hyperlipoproteinemia.
Hypolipoproteinemia
SpecialtyEndocrinology
Hypolipoproteinemia, hypolipidemia, or hypolipidaemia (British English) is a form of dyslipidemia that is defined by abnormally lowered levels of any or all lipids and/or lipoproteins in the blood. It occurs through genetic disease (namely, hypoalphalipoproteinemia and hypobetalipoproteinemia), malnutrition, malabsorption, wasting disease, cancer, hyperthyroidism, and liver disease.
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Critical illness
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Causes[edit]
Causes of hypolipidemia include:
* Hypobetalipoproteinemia (low levels of LDL cholesterol or apolipoprotein B)
* Malnutrition
* Malabsorption
* Wasting disease
* Certain cancers
* Hyperthyroidism (an overactive thyroid)
* Liver disease
## Diagnosis[edit]
It can be diagnosed via blood study that identifies fat particles. The patient must fast overnight to prevent interference from fat in the blood due to food intake. The criteria for this (without the involvement of cholesterol-lowering drugs) are total cholesterol levels below 120 mg/dL and LDL cholesterol levels under 50 mg/dL.[1]
### Critical illness[edit]
In the setting of critical illness, low cholesterol levels are predictive of clinical deterioration, and are correlated with altered cytokine levels.[2]
In humans with genetic loss-of-function variants in one copy of the ANGPTL3 gene, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").[3]
Hooft disease is a rare condition evidenced by low blood lipid level, red rash and mental and physical retardation.
## Treatment[edit]
Vitamin E supplements have shown to help children with the deficiency.
## See also[edit]
* Hypercholesterolemia
* Primary hyperlipoproteinemia
* ANGPTL3
## References[edit]
1. ^ The Merck Manual of Diagnosis of Therapy, 18th edition. 2006.
2. ^ Gordon BR, Parker TS, Levine DM, et al. (2001). "Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients". Crit. Care Med. 29 (8): 1563–8. doi:10.1097/00003246-200108000-00011. PMID 11505128.
3. ^ Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, et al. (2010). "Exome Sequencing, ANGPTL3Mutations, and Familial Combined Hypolipidemia". New England Journal of Medicine. 363 (23): 2220–2227. doi:10.1056/NEJMoa1002926. PMC 3008575. PMID 20942659.
## External links[edit]
Classification
D
* ICD-10: E78.6
* ICD-9-CM: 272.5
* MeSH: D007009
* SNOMED CT: 363140000
* v
* t
* e
Inborn error of lipid metabolism: dyslipidemia
Hyperlipidemia
* Hypercholesterolemia/Hypertriglyceridemia
* Lipoprotein lipase deficiency/Type Ia
* Familial apoprotein CII deficiency/Type Ib
* Familial hypercholesterolemia/Type IIa
* Combined hyperlipidemia/Type IIb
* Familial dysbetalipoproteinemia/Type III
* Familial hypertriglyceridemia/Type IV
* Xanthoma/Xanthomatosis
Hypolipoproteinemia
Hypoalphalipoproteinemia/HDL
* Lecithin cholesterol acyltransferase deficiency
* Tangier disease
Hypobetalipoproteinemia/LDL
* Abetalipoproteinemia
* Apolipoprotein B deficiency
* Chylomicron retention disease
Lipodystrophy
* Barraquer–Simons syndrome
Other
* Lipomatosis
* Adiposis dolorosa
* Lipoid proteinosis
* APOA1 familial renal amyloidosis
This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypolipoproteinemia
|
c0020623
| 7,521 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypolipoproteinemia
| 2021-01-18T18:28:22 |
{"gard": ["8394"], "mesh": ["D007009"], "umls": ["C0020623"], "orphanet": ["181431"], "wikidata": ["Q5959735"]}
|
Coloboma of optic disc is a rare, genetic, developmental defect of the eye characterized by a unilateral or bilateral, sharply demarcated, bowl-shaped, glistening white excavation on the optic disc (typically decentered inferiorly) which usually manifests with varying degrees of reduced visual acuity. It can occur isolated or may associate other ocular (e.g. retinal detachment, retinoschisis-like separation) or systemic anomalies (e.g. renal).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Coloboma of optic disc
|
c0155299
| 7,522 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98947
| 2021-01-23T17:20:39 |
{"gard": ["1438"], "mesh": ["C535970"], "icd-10": ["Q14.2"], "synonyms": ["Coloboma of optic papilla"]}
|
A rare infantile-onset neurometabolic disease characterized by dystonia, parkinsonism, nonambulation, autonomic dysfunction, developmental delay and mood disturbances.
## Epidemiology
The prevalence is unknown. It has been described in 8 patients from one Saudi Arabian family to date.
## Clinical description
Disease onset presents in infancy with hypotonia, loss of acquired head control and persistent crying and eye deviation. Motor development is delayed and later manifestations include severe parkinsonism, dystonia, ataxia, oculogyric crises, sleep and mood disturbances, temperature instability, excessive diaphoresis, ptosis and postural hypotension. Symptoms show no diurnal variation, do not improve with intake of vitamin B12 or folinic acid and worsened after administration of L-dopa.
## Etiology
Brain dopamine-serotonin vesicular transport disease is caused by a mutation in the SLC18A2 gene (10q25), encoding the vesicular monoamine transporter 2 (VMAT2) which is responsible for the transport of dopamine and serotonin into synaptic vesicles. Mutations in this gene lead to the impairment of VMAT2 and consequently to problems with motor control, autonomic functioning and mood regulation.
## Genetic counseling
It is inherited in an autosomal recessive manner, and genetic counseling is recommended.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Brain dopamine-serotonin vesicular transport disease
|
c4303546
| 7,523 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352649
| 2021-01-23T18:37:23 |
{"omim": ["618049"], "icd-10": ["G25.8"]}
|
Pfeiffer syndrome type 2 (PS2) is a frequent and severe type of Pfeiffer syndrome (PS; see this term), characterized by cloverleaf skull, severe associated functional disorders, and hand/foot and elbow/knee abnormalities.
## Epidemiology
The exact annual incidence of this form of PS is not known but the incidence of all forms of PS is 1/100,000.
## Clinical description
Patients with PS2 present with cloverleaf skull (trilobated skull deformity) that can cause limited brain growth and associated neurological dysfunction as well as significant upper respiratory compromise. The second main characteristic is broad medially deviated thumbs and halluces and variable brachydactyly and syndactyly, as well as ankylosis of the elbow or knee. Neurological manifestations such as hydrocephalus and seizures are a major source of morbidity. Developmental and intellectual delays are common. Extreme proptosis associated with the cloverleaf deformity causes exposure keratopathy. Additional ocular signs include optic atrophy, ptosis, strabismus, iris coloboma, refractive errors, cataracts and amblyopia. Respiratory tract abnormalities such as cleft palate, choanal stenosis or atresia and laryngotracheal malformations may also be present. Resultant airway obstruction and obstructive sleep apnea are a significant source of morbidity. Patients with cerebral or cerebellar hernia, intestinal malrotation, malposition of the anus, hydronephrosis, bifid scrotum, and hypoplastic gall bladder have also been reported. Given the severity of the disease manifestations and associated complications, the prognosis of this type of PS is poor, with a high risk of early demise, although the potential for long-term survival may be increased by aggressive early treatment. Causes of death are mainly respiratory and neurological complications.
## Etiology
Mutations in the FGFR2 gene (10q25.3-q26) involved in embryonic developmental cell signaling have been found to be causative in PS2. FGFR2 mutations are most commonly detected (69% in one study) followed by FGFR1 (8%).
## Genetic counseling
Pfeiffer syndrome follows an autosomal dominant pattern of inheritance but is generally caused by de novo mutations, especially in the severe forms of the syndrome. Genetic counseling should be provided to affected families.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pfeiffer syndrome type 2
|
c0220658
| 7,524 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93259
| 2021-01-23T17:11:35 |
{"mesh": ["D000168"], "omim": ["101600"], "icd-10": ["Q87.0"]}
|
A number sign (#) is used with this entry because of evidence that familial hyperinsulinemic hypoglycemia-6 (HHF6) is caused by heterozygous mutation in the glutamate dehydrogenase (GDH) gene (GLUD1; 138130) on chromosome 10q23.
For a phenotypic description and a discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450).
Clinical Features
A distinct syndrome of hyperinsulinism and hyperammonemia in 3 unrelated children was described by Zammarchi et al. (1996) and Weinzimer et al. (1997). In addition, Zammarchi et al. (1996) suggested that the defect involved leucine hypersensitivity. Hsu et al. (2001) studied 8 children and 6 adults with hypoglycemia due to congenital hyperinsulinism combined with persistent unexplained hyperammonemia. In each of these cases, known metabolic disorders were ruled out. All had dominantly expressed mutations of glutamine dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with hyperinsulinism/hyperammonemia showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with hyperinsulinism/hyperammonemia and control subjects. Hsu et al. (2001) concluded that the postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the hyperinsulinism/hyperammonemia syndrome.
Kelly et al. (2001) postulated that children with hyperinsulinism/hyperammonemia syndrome would have exaggerated acute insulin responses to leucine in the postabsorptive state. As hyperglycemia increases beta-cell guanosine triphosphate (GTP), they also postulated that high glucose concentrations would extinguish abnormal responsiveness to leucine in hyperinsulinism/hyperammonemia syndrome patients. After an overnight fast, 7 patients had acute insulin response to leucine administered intravenously. Four patients then had acute insulin responses to leucine repeated at hyperglycemia. High blood glucose suppressed their abnormal baseline acute insulin responses to leucine. The authors concluded that protein-induced hypoglycemia in hyperinsulinism/hyperammonemia syndrome patients may be prevented by carbohydrate loading before protein consumption.
De Lonlay et al. (2001) studied 12 unrelated patients with hyperinsulinism and hyperammonemia and observed clinically heterogeneous phenotypes, with neonatal- and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia was constant and not influenced by oral protein, by protein- and leucine-restricted diet, or by sodium benzoate or N-carbamylglutamate administration. Mean basal GDH activity in cultured lymphocytes did not differ between patients and controls, but the sensitivity of GDH activity to inhibition by GTP was reduced in all patient lymphoblast cultures. The activating effect of leucine on GDH activity varied among the patients; 4 patients had a significant decrease of sensitivity that correlated with a negative clinical response to dietary leucine.
Ihara et al. (2005) reported a Japanese girl who presented in infancy with delayed growth and hyperammonemia. Liver biopsy showed decreased activity of carbamoyl phosphate synthetase-1 (CPS1; 608307), and she was given a diagnosis of CPS1 deficiency (237300) based on enzymatic studies. Her blood glucose was relatively low on retrospective analysis. Treatment with protein restriction, sodium benzoate, and arginine failed to reduce the ammonia throughout childhood. At age 15 years, she showed borderline intelligence, and biochemical studies showed low serum glucose and inappropriately high insulin. The correct diagnosis of hyperinsulinism-hyperammonemia syndrome due to a de novo heterozygous GLUD1 mutation was confirmed by genetic analysis (S445L; 138130.0002). Ihara et al. (2005) could not explain the secondary CPS1 enzymatic deficiency in this patient, but suggested that the urea cycle may not have been functioning sufficiently in this patient.
Pathogenesis
Stanley et al. (1997) postulated that the hyperinsulinism-hyperammonemia syndrome is due to excessive oxidation of glutamate by glutamate dehydrogenase, since depletion of hepatic glutamate would reduce synthesis of N-acetylglutamate needed to stimulate ureagenesis. Moreover, leucine-mediated insulin release involves allosteric activation of GLUD. Mutations of GLUD1 cause the hyperinsulinism/hyperammonemia syndrome by desensitizing glutamate dehydrogenase to allosteric inhibition by GTP. Normal allosteric activation of GLUD1 by leucine is thus uninhibited.
Based on enzymatic studies on lymphoblasts, MacMullen et al. (2001) concluded that allosteric regulation of GDH as a control site for amino acid-stimulated insulin secretion is important and that the GTP-binding site is essential for regulation of GDH activity by both GTP and ATP.
Molecular Genetics
Stanley et al. (1997) studied GLUD activity and cDNA using cultured lymphoblasts from 2 infants with hyperinsulinism and hyperammonemia and their parents. In these patients, heterozygous mutations were found in the GLUD1 gene (138130.0001, 138130.0002). The C-terminal region affected by the mutations was known to confer responsiveness to allosteric regulators of GLUD activity. These unusual mutations resulted in a gain rather than a loss of enzyme function. In their report of 4 sporadic and 2 familial cases, Stanley et al. (1998) found 5 missense mutations clustered within a range of 10 codons in exons 11 and 12 of the GLUD1 gene, which predicted an effect on the presumed allosteric domain of the enzyme (see, e.g., 138130.0003-138130.0005). All of these mutations were associated with a diminished inhibitory effect of GTP on glutamate dehydrogenase activity.
In family 2 with hyperinsulinemic hypoglycemia studied by Thornton et al. (1998), Glaser et al. (1998) identified the S448P mutation in the GLUD1 gene.
Miki et al. (2000) performed mutation analysis of 5 unrelated Japanese patients (3 girls and 2 boys) with hyperinsulinism-hyperammonemia syndrome. All had convulsions or loss of consciousness resulting from hypoglycemia before the age of 1 year and asymptomatic, minimally elevated plasma ammonia levels. Heterozygous missense mutations were found in all. Three patients had a previously identified mutation, ser445 to leu (138130.0002), located in the allosteric domain. Two others were heterozygous for missense mutations within the catalytic domain of the gene (138130.0006 and 138130.0007). The site of the mutations was not correlated with the severity of hypoglycemia.
Santer et al. (2001) investigated 14 patients from 7 European families with mild hyperinsulinism. In 1 of the families, a novel heterozygous missense mutation in exon 6 (R221C; 138130.0008) was detected, and in all other cases from 6 unrelated families, the novel heterozygous missense mutation R269H (138130.0009) was found in exon 7. When glutamate dehydrogenase activity was measured in lymphocytes isolated from affected patients, both mutations were shown to result in a normal basal activity but a diminished sensitivity to GTP. The observation of the high prevalence of the exon 7 mutation both in familial and in sporadic cases of hyperinsulinism-hyperammonemia syndrome suggested a mutation hotspot and justified mutation screening for this mutation by mismatch PCR-based restriction enzyme digestion in patients with hyperinsulinism. In the 7 families with hyperinsulinism-hyperammonemia syndrome studied by Santer et al. (2001), 4 had more than 1 affected member. In 8 of 14 cases, hyperammonemia was documented, and 8 cases had signs of significant leucine sensitivity.
In 65 hyperinsulinism/hyperammonemia probands screened for GDH mutations, MacMullen et al. (2001) identified 19 (29%) who had mutations in a domain encoded by exons 6 and 7. Six new mutations were found. In all 5 mutations tested, lymphoblast GDH showed reduced sensitivity to allosteric inhibition by GTP, consistent with a gain of enzyme function. Studies of ATP allosteric effects on GDH showed a triphasic response with a decrease in high affinity inhibition of enzyme activity in hyperinsulinism/hyperammonemia lymphoblasts. All of the residues altered by exons 6 and 7 hyperinsulinism/hyperammonemia mutations lie in the GTP-binding domain of the enzyme.
De Lonlay et al. (2001) analyzed the GLUD1 gene in 11 unrelated patients with hyperinsulinism/hyperammonemia and identified 6 different heterozygous missense mutations in 10 patients. Three mutations were located within and 3 outside the GTP-binding site, without any correlation between phenotype and genotype.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, hypoglycemic \- Loss of consciousness due to hypoglycemia \- Mental retardation due to repeated episodes of hypoglycemia ENDOCRINE FEATURES \- Hyperinsulinemic hypoglycemia LABORATORY ABNORMALITIES \- Hypoglycemia \- Hyperinsulinemia \- Hyperammonemia, asymptomatic (2-5 times normal) MISCELLANEOUS \- Genetic heterogeneity (see HHF1 256450 ) \- Mean age at onset of hypoglycemia may be delayed (median, 9 months, diagnosis sometimes made in adulthood) MOLECULAR BASIS \- Caused by mutations in the glutamate dehydrogenase gene (GLUD1, 138130.0001 ) ▲ 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
|
HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 6
|
c1847555
| 7,525 |
omim
|
https://www.omim.org/entry/606762
| 2019-09-22T16:10:04 |
{"doid": ["0070217"], "mesh": ["C538375"], "omim": ["606762"], "orphanet": ["35878"], "synonyms": ["Alternative titles", "HYPERINSULINISM-HYPERAMMONEMIA SYNDROME", "HI/HA syndrome"], "genereviews": ["NBK1375"]}
|
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Iodine deficiency
SpecialtyEndocrinology
Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as cretinism due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.
Iodine is an essential dietary mineral for neurodevelopment among children.[1] The thyroid hormones thyroxine and triiodothyronine contain iodine. In areas where there is little iodine in the diet, typically remote inland areas where no marine foods are eaten, iodine deficiency is common. It is also common in mountainous regions of the world where food is grown in iodine-poor soil.
Prevention includes adding small amounts of iodine to table salt, a product known as iodized salt. Iodine compounds have also been added to other foodstuffs, such as flour, water and milk, in areas of deficiency.[2] Seafood is also a well known source of iodine.[3]
In the U.S., the use of iodine has decreased over concerns of overdoses since mid-20th century, and the iodine antagonists bromine, perchlorate and fluoride have become more ubiquitous.[4] In particular, around 1980 the practice of using potassium iodate as dough conditioner in bread and baked goods was gradually replaced by the use of other conditioning agents[5] such as bromide.[citation needed]
Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010[update] (2.7% of the population).[6] It resulted in 2700 deaths in 2013 up from 2100 deaths in 1990.[7]
## Contents
* 1 Signs and symptoms
* 1.1 Goiter
* 1.2 Congenital iodine deficiency syndrome
* 1.3 Fibrocystic breast changes
* 2 Risk factors
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 7.1 Deficient populations
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
### Goiter[edit]
Main article: Goiter
A low amount of thyroxine (one of the two thyroid hormones) in the blood, due to lack of dietary iodine to make it, gives rise to high levels of thyroid stimulating hormone (TSH), which stimulates the thyroid gland to increase many biochemical processes; the cellular growth and proliferation can result in the characteristic swelling or hyperplasia of the thyroid gland, or goiter. In mild iodine deficiency, levels of triiodothyronine (T3) may be elevated in the presence of low levels of levothyroxine, as the body converts more of the levothyroxine to triiodothyronine as a compensation. Some such patients may have a goiter, without an elevated TSH. The introduction of iodized salt since the early 1900s has eliminated this condition in many affluent countries; however, in Australia, New Zealand, and several European countries, iodine deficiency is a significant public health problem.[8] It is more common in developing countries. Public health initiatives to lower the risk of cardiovascular disease have resulted in lower discretionary salt use at the table. Additionally, there is a trend towards consuming more processed foods in western countries.[citation needed] The noniodized salt used in these foods means that people are less likely to obtain iodine from adding salt during cooking.
Goiter is said to be endemic when the prevalence in a population is > 5%, and in most cases goiter can be treated with iodine supplementation. If goiter is untreated for around five years, however, iodine supplementation or thyroxine treatment may not reduce the size of the thyroid gland because the thyroid is permanently damaged.
### Congenital iodine deficiency syndrome[edit]
Main article: Congenital iodine deficiency syndrome
Congenital iodine deficiency syndrome, previously known as cretinism, is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deafness, squint, disorders of stance and gait and stunted growth due to hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and their mentally disabled children.[9]
As a result of restricted diet, isolation, intermarriage, etc., as well as low iodine content in their food, children often had peculiar stunted bodies and retarded mental faculties, a condition later known to be associated with thyroid hormone deficiency. Diderot, in his 1754 Encyclopédie, described these patients as "crétins". In French, the term "crétin des Alpes" also became current, since the condition was observed in remote valleys of the Alps in particular. The word cretin appeared in English in 1779.
While reporting recent progress towards overcoming iodine-deficiency disorders worldwide, The Lancet noted: "According to World Health Organization, in 2007, nearly 2 billion individuals had insufficient iodine intake, a third being of school age." A conclusion was made that the single most preventable cause of intellectual disability is that of iodine deficiency.[10]
### Fibrocystic breast changes[edit]
Main article: Fibrocystic breast changes
There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen.[11][12] In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet.[11][12] In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes.[11][13][unreliable medical source?]
Protective effects of iodine on breast cancer have been postulated[by whom?] from epidemiologic evidence and described in animal models.[14][unreliable medical source?][15][unreliable medical source?][16] In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.[16][citation needed]
## Risk factors[edit]
Following is a list of potential risk factors that may lead to iodine deficiency:[17]
1. Low dietary iodine
2. Selenium deficiency
3. Pregnancy [18]
4. Exposure to radiation
5. Increased intake/plasma levels of goitrogens, such as calcium
6. Sex (higher occurrence in women)
7. Smoking tobacco
8. Alcohol (reduced prevalence in users)
9. Oral contraceptives (reduced prevalence in users)
10. Perchlorates
11. Thiocyanates
12. Age (for different types of iodine deficiency at different ages)
## Pathophysiology[edit]
Iodine accounts for 65% of the molecular weight of T4 and 59% of T3. There is a total of 15–20 mg of iodine in the human body, primarily concentrated in thyroid tissue and hormones. Thirty percent of iodine is distributed in other tissues, including the mammary glands, eyes, gastric mucosa, choroid plexus, arterial walls, the cervix, and salivary glands. In the cells of these tissues, iodide enters directly by sodium-iodide symporter (NIS).
* Venturi S, Guidi A, Venturi M (1996). "[Extrathyroid iodine deficiency disorders: what is the real iodine requirement?]"". Le Basi Razionali della Terapia. 16: 267–275.
* Pellerin P (1961). "La tecnique d'autoradiographie anatomique a la temperature de l'azote liquide". Path Biol. 232 (9): 233–252.
## Diagnosis[edit]
Sequence of 123-iodide human scintiscans after an intravenous injection, (from left) after 30 minutes, 20 hours, and 48 hours. A high and rapid concentration of radio-iodide is evident in the periencephalic and cerebrospinal fluid (left), salivary glands, oral mucosa and the stomach. In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes, to 5.8% after 48 hours, of the total injected dose.[19]
The diagnostic workup of a suspected iodine deficiency includes signs and symptoms as well as possible risk factors mentioned above. A 24-hour urine iodine collection is a useful medical test, as approximately 90% of ingested iodine is excreted in the urine.[20] For the standardized 24-hour test, a 50 mg iodine load is given first, and 90% of this load is expected to be recovered in the urine of the following 24 hours. Recovery of less than 90% is taken to mean high retention, that is, iodine deficiency. The recovery may, however, be well less than 90% during pregnancy, and an intake of goitrogens can alter the test results.[21]
If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used.[20] However, the 24-hour test is found to be more reliable.[22]
A general idea of whether a deficiency exists can be determined through a functional iodine test in the form of an iodine skin test. In this test, the skin is painted with an iodine solution: if the iodine patch disappears quickly, this is taken as a sign of iodine deficiency. However, no accepted norms exist on the expected time interval for the patch to disappear, and in persons with dark skin color the disappearance of the patch may be difficult to assess. If a urine test is taken shortly after, the results may be altered due to the iodine absorbed previously in a skin test.[21]
## Treatment[edit]
Iodine supplements
Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish. For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.[20]
The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men, it is somewhat less at 150 µg.[20]
Nonetheless, there is a lack of evidence on iodine fortification in foods, beverages, condiments, or seasonings other than salt in preventing goiter or improving physical development. On the other hand, such a measure may increase iodine concentration in urine.[23]
However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Wolff–Chaikoff effect) occurs.[24] Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities.[25] In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimoto's thyroiditis[26] and Graves' disease[27]).
## Prognosis[edit]
With iodine supplementation, goiters caused by iodine deficiency decrease in size in very young children and pregnant women. Generally, however, long-standing goiters caused by iodine deficiency respond with only small amounts of shrinkage after iodine supplementation, and patients are at risk for developing hyperthyroidism.[20]
## Epidemiology[edit]
Deaths due to iodine deficiency per million persons in 2012
0-0
1-1
2-3
4-18
Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2004.[28]
no data
<50
50-100
100-150
150-200
200-250
250-300
300-350
350-400
400-450
450-500
500-750
>750
Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010[update] (2.7% of the population).[6] Certain areas of the world, due to natural deficiency and unavailability of iodine, are severely affected by iodine deficiency, which affects approximately two billion people worldwide. It is particularly common in the Western Pacific, South-East Asia and Africa. Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education of salt producers and sellers and a communication campaign directed at the public. The cost of adding iodine to salt is negligible—"Only a few cents a ton."[29]
Iodine deficiency has largely been confined to the developing world for several generations, but reductions in salt consumption and changes in dairy processing practices eliminating the use of iodine-based disinfectants have led to increasing prevalence of the condition in Australia and New Zealand in recent years. A proposal to mandate the use of iodized salt in most commercial breadmaking was adopted in Australia in October 2009.[30] In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient.[31] The study's authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".[31]
Micronutrient deficiencies, including iodine deficiency, impair the development of intelligence. Lacking iodine during human development causes a fall, in average, of 12 intelligence quotient (IQ) points in China.[32] A study of U.S. military data collected during the First and Second World Wars found that the introduction of salt iodization in the U.S. in the 1920s resulted in an increase in IQ, by approximately one standard deviation, for the quarter of the U.S. population most deficient in iodine, explaining about "one decade's worth of the upward trend in IQ" in the U.S. (i.e., the Flynn effect).[33] The same study documented "a large increase in thyroid-related deaths following the countrywide adoption of iodized salt, which affected mostly older individuals in localities with high prevalence of iodine deficiency."[33]
In iodine-deficient or mildly iodine-deficient areas of Europe, iodine deficiency is frequent during pregnancy despite the widespread use of iodised salt, posing risks to the neurodevelopment of foetuses.[34] In one study performed in a mildly iodine-deficient area, iodine deficiency was found to be present in more than half of breastfeeding women; in contrast, the majority of their newborns had iodine excess, mostly due to neonatal exposure to iodine-containing disinfectants.[35] A 2014 meta-analysis found that iodine supplementation "improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children, even in marginally iodine-deficient areas."[36]
### Deficient populations[edit]
In areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency gives rise to hypothyroidism, symptoms of which are extreme fatigue, goiter, mental slowing, depression, weight gain, and low basal body temperatures.[37]
Iodine deficiency is the leading cause of preventable mental retardation, a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of the element. The addition of iodine to table salt has largely eliminated this problem in the wealthier nations, but as of March 2006, iodine deficiency remained a serious public health problem in the developing world.[38]
Iodine deficiency is also a problem in certain areas of Europe. In Germany it has been estimated to cause a billion dollars in health care costs per year.[13] A modelling analysis suggests universal iodine supplementation for pregnant women in England may save £199 (2013 UK pounds) to the health service per pregnant woman and save £4476 per pregnant woman in societal costs.[39]
Iodine deficiency was previously a common disease in Norway, because the content of iodine in the drinking water was low. Before 1950 goiter was a widespread disease caused by iodine deficiency.[40] Up to 80 per cent of the population were affected in inland areas. In the coastal communities, saltwater fish were an important part of the diet, and because of the presence of iodine in seawater, goiter was less common than in the inland districts. From the 1950s, Norwegians started adding iodine to dairy cow feed. Since milk was an essential part of the Norwegian diet, the incidence of goiter decreased in the population.[40]
## See also[edit]
* Basil Hetzel
* Lugol's iodine
* International Council for the Control of Iodine Deficiency Disorders
## References[edit]
1. ^ "Risiko For Jodmangel i Norge" (PDF). Ernæringsrådet (in Norwegian). June 2016.
2. ^ Creswell J. Eastman; Michael Zimmermann (12 February 2014). "The Iodine Deficiency Disorders". Thyroid Disease Manager. Retrieved 2016-12-11.
3. ^ "Iodine in Seaweed". Archived from the original on 2012-07-31. Retrieved 2008-01-04.
4. ^ Meletis, C. D. (2011). "Iodine: Health Implications of Deficiency". Journal of Evidence-Based Complementary & Alternative Medicine. 16 (3): 190–194. doi:10.1177/2156587211414424. ISSN 1533-2101.
5. ^ K. Smith (24 August 1988). Trace Minerals in Foods. CRC Press. pp. 273–. ISBN 978-0-8247-7835-4.
6. ^ a b Vos, T; Flaxman, A. D.; Naghavi, M; Lozano, R; Michaud, C; Ezzati, M; Shibuya, K; Salomon, J. A.; Abdalla, S; Aboyans, V; Abraham, J; Ackerman, I; Aggarwal, R; Ahn, S. Y.; Ali, M. K.; Alvarado, M; Anderson, H. R.; Anderson, L. M.; Andrews, K. G.; Atkinson, C; Baddour, L. M.; Bahalim, A. N.; Barker-Collo, S; Barrero, L. H.; Bartels, D. H.; Basáñez, M. G.; Baxter, A; Bell, M. L.; Benjamin, E. J.; et al. (Dec 15, 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMC 6350784. PMID 23245607.
7. ^ GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–171. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
8. ^ Andersson M, Takkouche B, Egli I, Allen HE, de Benoist B (2005). "Current global iodine status and progress over the last decade towards the elimination of iodine deficiency". Bull. World Health Organ. 83 (7): 518–25. PMC 2626287. PMID 16175826.
9. ^ T.E.C., Jr. (August 1, 1974). "Paracelsus on What the Physician Should Know". Pediatrics. American Academy of Pediatrics. 54 (2). Retrieved 2008-12-05.
10. ^ The Lancet (12 July 2008). "Iodine deficiency—way to go yet". The Lancet. 372 (9633): 88. doi:10.1016/S0140-6736(08)61009-0. PMID 18620930. S2CID 5416860. Retrieved 2008-12-05.
11. ^ a b c Cann, Stephen A.; van Netten, Johannes P.; van Netten, Christiaan (2000). "Hypothesis: iodine, selenium and the development of breast cancer". Cancer Causes and Control (review). 11 (2): 121–127. doi:10.1023/A:1008925301459. ISSN 0957-5243. PMID 10710195. S2CID 2665461.
12. ^ a b Joseph E. Pizzorno; Michael T. Murray (14 September 2012). Textbook of Natural Medicine. Elsevier Health Sciences. p. 1371. ISBN 978-1-4377-2333-5.
13. ^ a b Patrick L (2008). "Iodine: deficiency and therapeutic considerations". Altern Med Rev. 13 (2): 116–27. PMID 18590348.
14. ^ "Iodine Monograph" (PDF). Alternative Medicine Review. 15 (3): 273–278. 2010. PMID 21155628.
15. ^ Venturi S (October 2001). "Is there a role for iodine in breast diseases?". Breast. 10 (5): 379–82. doi:10.1054/brst.2000.0267. PMID 14965610.
16. ^ a b Aceves C, Anguiano B, Delgado G (April 2005). "Is iodine a gatekeeper of the integrity of the mammary gland?". Journal of Mammary Gland Biology and Neoplasia (review). 10 (2): 189–96. doi:10.1007/s10911-005-5401-5. PMID 16025225. S2CID 16838840.
17. ^ Knudsen N, Laurberg P, Perrild H, Bülow I, Ovesen L, Jørgensen T (October 2002). "Risk factors for goiter and thyroid nodules". Thyroid. 12 (10): 879–88. doi:10.1089/105072502761016502. PMID 12487770.
18. ^ ASkeaff SA (Feb 2011). "Iodine Deficiency in Pregnancy: The Effect on Neurodevelopment in the Child". 3 (2). Nutrients. doi:10.3390/nu3020265. Retrieved 10 May 2020. Cite journal requires `|journal=` (help)
19. ^ Venturi, S.; Donati, F.M.; Venturi, A.; Venturi, M. (2000). "Environmental Iodine Deficiency: A Challenge to the Evolution of Terrestrial Life?". Thyroid. 10 (8): 727–9. doi:10.1089/10507250050137851. PMID 11014322.
20. ^ a b c d e Stephanie L. Lee; Elizabeth N. Pearce; Sonia Ananthakrishnan (16 December 2015). "Iodine Deficiency". Medscape. Retrieved 2016-12-11.
21. ^ a b Richard S. Lord; J. Alexander Bralley (2008). Laboratory Evaluations for Integrative and Functional Medicine. Metametrix Institute. pp. 107–108. ISBN 978-0-9673949-4-7.
22. ^ Richard S. Lord; J. Alexander Bralley (2008). Laboratory Evaluations for Integrative and Functional Medicine. Metametrix Institute. p. 106. ISBN 978-0-9673949-4-7.
23. ^ Alvin-R-Santos,J, Christoforou A, Trieu K, McKenzie BL, Downs S, Billot L, Webster J, Li M (12 February 2019). "Iodine Fortification of Foods and Condiments, Other Than Salt, for Preventing Iodine Deficiency Disorders". Cochrane Database of Systematic Reviews. 2 (2): CD010734. doi:10.1002/14651858.CD010734.pub2. PMC 6370918. PMID 30746700.CS1 maint: multiple names: authors list (link)
24. ^ Sabyasachi Sircar (2008). Principles of Medical Physiology. Thieme. p. 513. ISBN 978-1-58890-572-7.
25. ^ Leung, Angela M.; Braverman, Lewis E. (2013). "Consequences of excess iodine". Nature Reviews Endocrinology. 10 (3): 136–142. doi:10.1038/nrendo.2013.251. ISSN 1759-5029. PMC 3976240. PMID 24342882.
26. ^ Rose NR, Bonita R, Burek CL (February 2002). "Iodine: an environmental trigger of thyroiditis". Autoimmunity Reviews. 1 (1–2): 97–103. CiteSeerX 10.1.1.326.5700. doi:10.1016/s1568-9972(01)00016-7. PMID 12849065.
27. ^ Laurberg, P.; Pedersen, K. M.; Vestergaard, H.; Sigurdsson, G. (1991). "High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland". Journal of Internal Medicine. 229 (5): 415–420. doi:10.1111/j.1365-2796.1991.tb00368.x. ISSN 0954-6820. PMID 2040867.
28. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.
29. ^ "In Raising the World's I.Q., the Secret's in the Salt", article by Donald G. McNeil, Jr., The New York Times, December 16, 2006.
30. ^ l "Iodine Fortification" Archived 2013-04-10 at the Wayback Machine, article appearing on March 5, 2013, from Food Standards.
31. ^ a b Vanderpump, M. P.; Lazarus, J. H.; Smyth, P. P.; Laurberg, P; Holder, R. L.; Boelaert, K; Franklyn, J. A.; British Thyroid Association UK Iodine Survey Group (11 June 2011). "Iodine status of UK schoolgirls: a cross-sectional survey". The Lancet. 377 (9782): 2007–12. doi:10.1016/S0140-6736(11)60693-4. PMID 21640375. S2CID 2234051.
32. ^ Qian M, Wang D, Watkins WE, et al. (2005). "The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China". Asia Pacific Journal of Clinical Nutrition. 14 (1): 32–42. PMID 15734706.
33. ^ a b James Feyrer, Dimitra Politi & David N. Weil (April 2017). "The Cognitive Effects of Micronutrient Deficiency: Evidence from Salt Iodization in the United States". Journal of the European Economic Association. 15 (2): 355–387.CS1 maint: uses authors parameter (link) CS1 maint: date and year (link)
34. ^ Trumpff, Caroline; De Schepper, Jean; Tafforeau, Jean; Van Oyen, Herman; Vanderfaeillie, Johan; Vandevijvere, Stefanie (2013). "Mild iodine deficiency in pregnancy in Europe and its consequences for cognitive and psychomotor development of children: A review" (PDF). Journal of Trace Elements in Medicine and Biology. 27 (3): 174–183. doi:10.1016/j.jtemb.2013.01.002. PMID 23395294.
35. ^ Yaman AK, Demirel F, Ermiş B, Pişkin IE (2013). "Maternal and neonatal urinary iodine status and its effect on neonatal TSH levels in a mildly iodine-deficient area". Journal of Clinical Research in Pediatric Endocrinology. 5 (2): 90–4. doi:10.4274/Jcrpe.997. PMC 3701928. PMID 23748060.
36. ^ Taylor PN, Okosieme OE, Dayan CM, Lazarus JH (January 2014). "Therapy of endocrine disease: Impact of iodine supplementation in mild-to-moderate iodine deficiency: systematic review and meta-analysis". European Journal of Endocrinology (review). 170 (1): R1–R15. doi:10.1530/EJE-13-0651. PMID 24088547.
37. ^ Felig, Philip; Frohman, Lawrence A. (2001). "Endemic Goiter". Endocrinology & metabolism. McGraw-Hill Professional. ISBN 978-0-07-022001-0.
38. ^ "Micronutrients — Iodine, Iron and Vitamin A". UNICEF.
39. ^ Monahan, Mark; Boelaert, Kristien; Jolly, Kate; Chan, Shiao; Barton, Pelham; Roberts, Tracy E (2015-01-01). "Costs and benefits of iodine supplementation for pregnant women in a mildly to moderately iodine-deficient population: a modelling analysis" (PDF). The Lancet Diabetes & Endocrinology. 3 (9): 715–722. doi:10.1016/s2213-8587(15)00212-0. PMID 26268911.
40. ^ a b "Fakta om jod" [Facts about iodine]. Folkehelseinstituttet (in Norwegian). Retrieved 2018-07-11.
## Further reading[edit]
* Kotwal A, Priya R, Qadeer I (2007). "Goiter and other iodine deficiency disorders: A systematic review of epidemiological studies to deconstruct the complex web". Arch. Med. Res. 38 (1): 1–14. doi:10.1016/j.arcmed.2006.08.006. PMID 17174717.
## External links[edit]
Classification
D
* ICD-10: E00–E02
* DiseasesDB: 6933
External resources
* eMedicine: med/1187
* v
* t
* e
Thyroid disease
Hypothyroidism
* Iodine deficiency
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Vitamins (A11)
Fat
soluble
A
* α-Carotene
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* Retinol#
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D
* D2
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* Ergocalciferol#
* D3
* 7-Dehydrocholesterol
* Previtamin D3
* Cholecalciferol#
* 25-hydroxycholecalciferol
* Calcitriol (1,25-dihydroxycholecalciferol)
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E
* Tocopherol
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K
* Naphthoquinone
* Phylloquinone (K1)#
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* Menadione (K3)‡
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* 4-Amino-2-methyl-1-naphthol (K5)‡
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Water
soluble
B
* B1
* Thiamine#
* B1 analogues
* Acefurtiamine
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* B2
* Riboflavin#
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* B5
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* Dexpanthenol
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* Pyridoxine#, Pyridoxal phosphate
* Pyridoxamine
* Pyritinol
* B7
* Biotin
* B9
* Folic acid#
* Dihydrofolic acid
* Folinic acid
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* B12
* Adenosylcobalamin
* Cyanocobalamin
* Hydroxocobalamin#
* Methylcobalamin
C
* Ascorbic acid#
* Dehydroascorbic acid
Combinations
* Multivitamins
* #WHO-EM
* ‡Withdrawn from market
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* †Phase III
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Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
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* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
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* Manganese
* Copper
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* Chromium
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Growth
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General
* Anorexia
* Weight loss
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* v
* t
* e
Dietary supplements
Types
* Amino acids
* Bodybuilding supplement
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* Herbal supplements
* Minerals
* Prebiotics
* Probiotics (Lactobacillus
* Bifidobacterium)
* Protein bar
* Vitamins
Vitamins and
chemical elements
("minerals")
* Retinol (Vitamin A)
* B vitamins
* Thiamine (B1)
* Riboflavin (B2)
* Niacin (B3)
* Pantothenic acid (B5)
* Pyridoxine (B6)
* Biotin (B7)
* Folic acid (B9)
* Cyanocobalamin (B12)
* Ascorbic acid (Vitamin C)
* Ergocalciferol and Cholecalciferol (Vitamin D)
* Tocopherol (Vitamin E)
* Naphthoquinone (Vitamin K)
* Calcium
* Choline
* Chromium
* Cobalt
* Copper
* Fluorine
* Iodine
* Iron
* Magnesium
* Manganese
* Molybdenum
* Phosphorus
* Potassium
* Selenium
* Sodium
* Sulfur
* Zinc
Other common
ingredients
* AAKG
* β-hydroxy β-methylbutyrate
* Carnitine
* Chondroitin sulfate
* Cod liver oil
* Copper gluconate
* Creatine
* Dietary fiber
* Echinacea
* Elemental calcium
* Ephedra
* Fish oil
* Folic acid
* Ginseng
* Glucosamine
* Glutamine
* Grape seed extract
* Guarana
* Iron supplements
* Japanese honeysuckle
* Krill oil
* Lingzhi
* Linseed oil
* Lipoic acid
* Milk thistle
* Melatonin
* Red yeast rice
* Royal jelly
* Saw palmetto
* Spirulina
* St John's wort
* Taurine
* Wheatgrass
* Wolfberry
* Yohimbine
* Zinc gluconate
Related articles
* Codex Alimentarius
* Enzyte
* Hadacol
* Herbal tea
* Nutraceutical
* Multivitamin
* Nutrition
Authority control
* LCCN: sh87000668
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Iodine deficiency
|
c0342199
| 7,526 |
wikipedia
|
https://en.wikipedia.org/wiki/Iodine_deficiency
| 2021-01-18T19:03:17 |
{"umls": ["C0342199"], "icd-10": ["E02", "E00"], "wikidata": ["Q18377123"]}
|
A number sign (#) is used with this entry because of evidence that idiopathic basal ganglia calcification-6 (IBGC6) is caused by heterozygous mutation in the XPR1 gene (605237) on chromosome 1q25.
Description
Idiopathic basal ganglia calcification is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive neuropsychiatric and movement disorders, although some patients remain asymptomatic. Clinical features can include dystonia, parkinsonism, gait abnormalities, psychosis, dementia, and chorea. Brain imaging shows calcifications of the basal ganglia and other brain regions (summary by Legati et al., 2015).
For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
Clinical Features
Boller et al. (1973) described palilalia, compulsive repetition of a phrase or word, in a mother and son with intracranial calcifications. Asymptomatic intracranial calcifications were present in other members of the family. In a later report, Boller et al. (1977) showed that 9 members of this family spanning 3 generations had bilateral calcifications of the basal ganglia. The family was of Swedish descent living in North America. The palilalia in the mother and son was accompanied by chorea and dementia beginning in the third or fourth decade. A third member was thought to show initial stages of a similar syndrome. Six members with calcifications but without neurologic signs were younger than 25 years. All 9 patients had normal calcium and phosphorus, and no evidence of endocrinologic or somatic abnormalities. Oliveira et al. (2004) excluded linkage to the IBGC1 locus on chromosome 14 in the family reported by Boller et al. (1977).
Legati et al. (2015) reported follow-up of the family reported by Boller et al. (1977). Features were variable, and included slurred speech, nervous affect, depression, concentration or memory complaints, and behavioral problems. One patient had sudden onset at age 44 and was severely affected and bedridden with speech impairment and seizures. At least 3 mutation carriers with a positive CT scan were asymptomatic, including 2 who were 16 and 20 years old. Four patients from 3 additional families with the disorder had similar features, including adult onset of depression, dysarthria, and cognitive impairment; 1 patient had a more severe course with visual hallucinations and parkinsonism. The disorder was progressive.
Inheritance
The transmission pattern of IBGC in the family reported by Boller et al. (1973, 1977) was consistent with autosomal dominant inheritance.
Molecular Genetics
In 9 affected members of a large family of Swedish origin with IBGC6 originally reported by Boller et al. (1977), Legati et al. (2015) identified a heterozygous missense mutation in the XPR1 gene (L145P; 605237.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Further sequencing of XPR1 in 86 patients with a similar disorder identified heterozygous pathogenic missense mutations in 5 patients from 4 unrelated families (605237.0002-605237.0004). In vitro functional expression studies showed that all the mutations impaired phosphate efflux to various degrees. Legati et al. (2015) postulated that inhibition of phosphate export would lead to increased intracellular phosphate concentration and intracellular calcium/phosphate precipitation.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Dysarthria \- Palilalia \- Memory impairment \- Cognitive impairment \- Dementia \- Gait impairment \- Involuntary movements \- Choreoathetosis \- Parkinsonism \- Seizures (in some patients) \- Calcium deposition in the basal ganglia, thalamus, cerebrum, and cerebellum Behavioral Psychiatric Manifestations \- Depression \- Nervous affect \- Behavioral abnormalities MISCELLANEOUS \- Adult onset \- Variable features \- Progressive disorder \- Some patients may be asymptomatic MOLECULAR BASIS \- Caused by mutation in the xenotropic and polytropic retrovirus receptor gene (XPR1, 605237.0001 ) ▲ 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
|
BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 6
|
c0393590
| 7,527 |
omim
|
https://www.omim.org/entry/616413
| 2019-09-22T15:48:56 |
{"omim": ["616413"], "orphanet": ["1980"], "genereviews": ["NBK1421"]}
|
## Description
Nasopharyngeal carcinoma is a multifactorial malignancy associated with both genetic and environmental factors. The cancer arises from the epithelium of the nasopharynx (summary by Tse et al., 2009).
For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to nasopharyngeal carcinoma, see NPCA1 (607107).
Mapping
In 3 generations of an American family of Scandinavian descent, Coffin et al. (1989, 1991) found 5 cases of nasopharyngeal carcinoma and 6 other malignancies. Moreover, there was a history of autoimmune disorders, including pernicious anemia, thyroid disease, and psoriasis, in this family. The authors observed an increased frequency of the HLA haplotype A1-B37-DR6 (see, e.g., HLA-A; 142800), which maps to chromosome 6p21, in affected family members.
Chan et al. (1983) found relative risks slightly over 2-fold for the haplotype A2,Bw46 and the antigen B17.
Lu et al. (1990) reported a linkage study based on affected sib pairs which suggested that a gene closely linked to the HLA region confers a greatly increased risk of nasopharyngeal carcinoma. The maximum likelihood estimate placed the relative risk at approximately 21.
Ooi et al. (1997) found an association of the HLA-Bw46 locus with increased risk of NPCA.
In a genomewide association study of 277 NPCA patients and 285 controls in the Taiwanese population, Tse et al. (2009) identified 12 significant SNPs mapping to chromosome 6p21.3. Associations were replicated in 2 independent sets of 339 NPC patients and 696 controls, and 296 NPC patients and 944 controls. All cases and controls were of Han Chinese origin. Two of the most significant SNPs were in the HLA-A gene rs2517713 and rs2975042 with combined p values of = 3.9 x 10(-20) and 1.6 x 10(-19), respectively. Tse et al. (2009) also detected significant associations between NPCA and a SNP in the GABBR1 (603540) gene in this chromosomal region: rs29232, (p = 8.97 x 10(-17)), which remained significant (p less than 5 x 10(-4)) after adjustment for age, gender, and HLA-related SNPs. Higher GABBR1 expression levels were found in tumor cells compared to adjacent epithelial cells. Two additional SNPs in the HLA-F gene (143110) also showed an association with NPCA (rs3129055, p = 7.36 x 10(-11); 9258122, 3.33 x 10(-10)).
Oncology \- Nasopharyngeal cancer Misc \- 100-fold higher frequency in southern China than Europe \- Males more frequently affected than females \- HLA linked gene confers greatly ineased risk Inheritance \- Questionably mendelian, but strong genetic factor involved ▲ 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
|
NASOPHARYNGEAL CARCINOMA, SUSCEPTIBILITY TO, 2
|
c0238301
| 7,528 |
omim
|
https://www.omim.org/entry/161550
| 2019-09-22T16:37:36 |
{"doid": ["9261"], "mesh": ["D009303"], "omim": ["161550"], "orphanet": ["150"]}
|
A number sign (#) is used with this entry because autosomal recessive mental retardation-38 (MRT38) is caused by homozygous mutation in the HERC2 gene (605837) on chromosome 15q13.
Clinical Features
Puffenberger et al. (2012) reported 7 patients of Amish or mixed Amish/Mennonite descent with global developmental delay affecting motor, speech, adaptive, and social development. Four had hypotonia and poor suck during infancy, and most had an unstable gait. All patients had behavioral abnormalities, including autistic features, aggression, self-injury, impulsivity, and distractibility. The only distinctive physical characteristic was blue irides. Puffenberger et al. (2012) noted some phenotypic similarities to Angelman syndrome (AS; 105830).
Harlalka et al. (2013) reported 15 additional Amish individuals, aged 11 months to 39 years, with this severe neurodevelopmental disorder. Features included global developmental delay, hypotonia, delayed walking with an unstable gait, absent or poor speech, and poor concentration with hyperactivity. Subtle dysmorphic features included plagiocephaly, prognathism, narrow palate, elongated hallux, sandal gap, and pronation of the feet. Most affected individuals had bright blue eyes. Four patients had seizures, and 3 of 6 who underwent brain imaging showed absence of the posterior half of the corpus callosum.
Inheritance
The transmission pattern of MRT38 in the families reported by Puffenberger et al. (2012) was consistent with autosomal recessive inheritance.
Mapping
By autozygosity mapping of individuals of Amish or mixed Amish/Mennonite descent with autosomal recessive mental retardation, Puffenberger et al. (2012) identified an 8.2-Mb minimal homozygous segment on chromosome 15q13 that was shared by all affected individuals.
Molecular Genetics
In 7 patients of Amish or mixed Amish/Mennonite descent with autosomal recessive mental retardation-38, Puffenberger et al. (2012) identified a homozygous missense mutation in the HERC2 gene (P594L; 605837.0004). The mutation was found by a combination of homozygosity mapping and exome sequencing. The mutation was not present in the dbSNP database or in 760 alleles from Amish and Mennonite controls. Cellular transfection studies showed that the mutant protein was less stable than wildtype and had a diffuse cytosolic localization with the formation of abnormal aggregates. Decreased abundance and/or activity of HERC2 could produce a toxic loss of E3 ubiquitin ligase activity, leading to decreased degradation of ARC (612461) and decreased postsynaptic glutamatergic AMPA receptor density. Puffenberger et al. (2012) noted that this pathophysiologic mechanism is similar to that thought to underlie Angelman syndrome (AS; 105830), one of a group of neurodevelopmental disorders mapping to chromosome 15q11-q13, which results from loss of UBE3A (601623). The individuals with MRT38 had some features similar to those of AS.
By genomewide linkage analysis and candidate gene analysis, Harlalka et al. (2013) identified a homozygous P594L mutation in the HERC2 gene (605837.0004) in 15 Amish patients with a neurodevelopmental disorder. The mutation, which was not present in the Exome Variant Server or 1000 Genomes Project databases, segregated with the disorder in the families. Two of 158 control chromosomes from the same Amish community carried the mutation, consistent with a founder effect. Patient fibroblasts showed a dramatic reduction in HERC2 protein levels due to mutant protein instability.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Plagiocephaly Face \- Prognathism Eyes \- Blue irides \- Strabismus Mouth \- Narrow palate SKELETAL Feet \- Sandal gap \- Pronation of the feet \- Elongated hallux MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Delayed ambulation \- Delayed adaptive hand use \- Poor language \- Seizures (in some patients) \- Gait instability \- Hypoplasia of the posterior corpus callosum (in some patients) Behavioral Psychiatric Manifestations \- Autistic features \- Hyperactivity \- Poor concentration \- Aggressive behavior \- Self-mutilation \- Impulsive behavior MISCELLANEOUS \- Onset in infancy \- Reported in individuals of Amish or Mennonite descent MOLECULAR BASIS \- Caused by mutation in the HECT domain and RCC1-like domain 2 (HERC2, 605837.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 38
|
c3809753
| 7,529 |
omim
|
https://www.omim.org/entry/615516
| 2019-09-22T15:51:50 |
{"doid": ["0060308"], "omim": ["615516"], "orphanet": ["329195"], "synonyms": ["Developmental delay with ASD and gait instability"]}
|
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Calcinosis
North Korean President Kim Il-sung's calcium deposit is noticeable on the back of his head in this rare newsreel still image during a diplomatic meeting between him and Chinese leader Mao Zedong in Beijing, 1970.
SpecialtyEndocrinology
Calcinosis is the formation of calcium deposits in any soft tissue. It is a rare condition that has many different causes. These range from infection and injury to systemic diseases like kidney failure.
## Contents
* 1 Types
* 1.1 Dystrophic calcification
* 1.2 Metastatic calcification
* 1.3 Tumoral calcinosis
* 2 See also
* 3 References
* 4 External links
## Types[edit]
### Dystrophic calcification[edit]
The most common type of calcinosis is dystrophic calcification. This type of calcification can occur as a response to any soft tissue damage, including that involved in implantation of medical devices.
### Metastatic calcification[edit]
Metastatic calcification involves a systemic calcium excess imbalance, which can be caused by hypercalcemia, kidney failure, milk-alkali syndrome, lack or excess of other minerals, or other causes.
### Tumoral calcinosis[edit]
The cause of the rare condition of tumoral calcinosis is not entirely understood. It is generally characterized by large, globular calcifications near joints.
## See also[edit]
* Calcinosis cutis
* Dermatomyositis
* Fahr's syndrome
* Hyperphosphatemia
* Primrose syndrome
* Scleroderma
## References[edit]
## External links[edit]
Classification
D
* ICD-9-CM: 275.4
* MeSH: D002114
* SNOMED CT: 6595006
* v
* t
* e
Electrolyte imbalances
Sodium
* High
* Salt poisoning
* Low
* Hypotonic
* Isotonic
* Cerebral salt-wasting syndrome
Potassium
* High
* Low
Chloride
* High
* Low
Calcium
* High
* Low
* Symptoms and signs
* Chvostek sign
* Trousseau sign
* Milk-alkali syndrome
* Disorders of calcium metabolism
* Calcinosis (Calciphylaxis, Calcinosis cutis)
* Calcification (Metastatic calcification, Dystrophic calcification)
* Familial hypocalciuric hypercalcemia
Phosphate
* High
* Low
Magnesium
* High
* Low
This article about a disease, disorder, or medical condition 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
|
Calcinosis
|
c0006663
| 7,530 |
wikipedia
|
https://en.wikipedia.org/wiki/Calcinosis
| 2021-01-18T18:29:33 |
{"mesh": ["D002114"], "umls": ["C0006663"], "icd-9": ["275.4"], "wikidata": ["Q239027"]}
|
A rare multiple congenital anomalies/dysmorphic syndrome characterized by early-onset progressive bone marrow failure with anemia, leukopenia, mild thrombopenia, and myelodysplastic features, as well as non-hematologic manifestations, such as developmental delay, cataracts, facial dysmorphism, short stature, and skeletal anomalies. Immunodeficiency primarily affects B-cells and may lead to increased susceptibility to infections. Additional reported features include dry skin and eczema, cardiac anomalies, hearing loss, and reduction of cerebral volume on brain imaging.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome
|
None
| 7,531 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=508542
| 2021-01-23T17:01:37 |
{"synonyms": ["MYSM1 deficiency"]}
|
Craniotelencephalic dysplasia is an extremely rare, genetic developmental defect during embryogenesis syndrome characterized by craniosynostosis with frontal encephalocele and various additional brain anomalies (severe hydrocephalus, agenesis of the corpus callosum, lissencephaly and polymicrogyria, parenchymal cysts, septo-optic dysplasia) resulting in marked cerebral dysfunction, seizures and very severe psychomotor delay. There have been no further descriptions in the literature since 1983.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Craniotelencephalic dysplasia
|
c1857471
| 7,532 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1528
| 2021-01-23T16:56:04 |
{"gard": ["1605"], "mesh": ["C535597"], "omim": ["218670"], "umls": ["C1857471"], "icd-10": ["Q04.3"]}
|
Primary coenzyme Q10 deficiency is a disorder that can affect many parts of the body, especially the brain, muscles, and kidneys. As its name suggests, the disorder involves a shortage (deficiency) of a substance called coenzyme Q10.
The severity, combination of signs and symptoms, and age of onset of primary coenzyme Q10 deficiency vary widely. In the most severe cases, the condition becomes apparent in infancy and causes severe brain dysfunction combined with muscle weakness (encephalomyopathy) and the failure of other body systems. These problems can be life-threatening. The mildest cases of primary coenzyme Q10 deficiency can begin as late as a person's sixties and often cause cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Other neurological abnormalities that can occur in primary coenzyme Q10 deficiency include seizures, intellectual disability, poor muscle tone (hypotonia), involuntary muscle contractions (dystonia), progressive muscle stiffness (spasticity), abnormal eye movements (nystagmus), vision loss caused by degeneration (atrophy) of the optic nerves or breakdown of the light-sensing tissue at the back of the eyes (retinopathy), and sensorineural hearing loss (which is caused by abnormalities in the inner ear). The neurological problems gradually get worse unless treated with coenzyme Q10 supplementation.
A type of kidney dysfunction called nephrotic syndrome is another common feature of primary coenzyme Q10 deficiency. It can occur with or without neurological abnormalities. Nephrotic syndrome occurs when damage to the kidneys impairs their function, which allows protein from the blood to pass into the urine (proteinuria). Other signs and symptoms of nephrotic syndrome include increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells in the body (anemia), abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with nephrotic syndrome. If not treated with coenzyme Q10 supplementation, affected individuals eventually develop irreversible kidney failure (end-stage renal disease).
A type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy) can also occur in primary coenzyme Q10 deficiency.
## Frequency
The prevalence of primary coenzyme Q10 deficiency is thought to be less than 1 in 100,000 people.
## Causes
Primary coenzyme Q10 deficiency is caused by mutations in genes that provide instructions for making proteins involved in the production (synthesis) of a molecule called coenzyme Q10. Collectively, they are called the COQ genes. Most of the identified mutations have occurred in the COQ2, COQ4, COQ6, COQ8A, and COQ8B genes. Smaller numbers of mutations in other COQ genes have also been found to cause primary coenzyme Q10 deficiency.
The coenzyme Q10 molecule has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.
Some mutations in the COQ genes greatly reduce or eliminate the production of the corresponding proteins; others change the structure of a protein, impairing its function. A lack of functional protein produced from any one of the COQ genes decreases the normal production of coenzyme Q10. Studies suggest that a shortage (deficiency) of coenzyme Q10 impairs oxidative phosphorylation and increases the vulnerability of cells to damage from free radicals. A deficiency of coenzyme Q10 may also disrupt the production of pyrimidines. These changes can cause cells throughout the body to malfunction, which may help explain the variety of organs and tissues that can be affected by primary coenzyme Q10 deficiency.
Coenzyme Q10 deficiency can also be caused by mutations in genes that are not directly related to the synthesis of coenzyme Q10. In these cases, the condition is referred to as secondary coenzyme Q10 deficiency. Secondary coenzyme Q10 deficiency is a common feature of certain other genetic conditions.
### Learn more about the genes associated with Primary coenzyme Q10 deficiency
* COQ2
* COQ4
* COQ6
* COQ8A
* COQ8B
Additional Information from NCBI Gene:
* COQ7
* COQ9
* PDSS1
* PDSS2
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary coenzyme Q10 deficiency
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c3551954
| 7,533 |
medlineplus
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https://medlineplus.gov/genetics/condition/primary-coenzyme-q10-deficiency/
| 2021-01-27T08:24:45 |
{"gard": ["10294", "10423"], "omim": ["607426", "614651", "614652", "612016", "614654", "614650", "616276", "616733", "615573"], "synonyms": []}
|
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: "Onyalai" – news · newspapers · books · scholar · JSTOR (February 2019) (Learn how and when to remove this template message)
Onyalai
Autopsy specimen of the heart of an individual with Onyalai. Heart shows haemorrhages throughout, particularly in the right atrium, which has been opened to reveal its interior surface.
SpecialtyHematology
Onyalai (Pronunciation: ō′nē-al′ā-ē) is a form of thrombocytopenia that affects some of the population in areas of central Africa.[1] Onyalai exhibits similarities to idiopathic thrombocytopenic purpura (ITP) but differs in pathogenesis. The affected age range is from less than a year to 70 years and seems to not be gender-specific in the same manner as ITP. Cases generally peak between 11 and 20 years old. Although the cause of onyalai is not known at this time, inadequate nutrition and/or the consumption of tainted food are suspected.[1]
## Signs and symptoms[edit]
Onyalai is an acute disease that results in the development of hematoma on oral mucous membranes. Hemorrhagic lesions may develop on the skin, including on the soles of the feet.[1] The patient does not initially appear to be in distress, which may result in a delay of diagnosis. As the disease progresses, hematuria and melena will develop. Epistaxis, petechiae and ecchymoses are common symptoms, as are subconjunctival bleeding and menorrhagia. On average, bleeding will persist for approximately eight days, and may reoccur.[1] Approximately 80 percent of cases will exhibit chronic thrombocytopenia. Periodic episodes of acute hemorrhage are also possible and may be severe, possibly leading to shock and death.[1]
## References[edit]
1. ^ a b c d e "Onyalai".[dead link]
This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Onyalai
|
None
| 7,534 |
wikipedia
|
https://en.wikipedia.org/wiki/Onyalai
| 2021-01-18T18:30:17 |
{"wikidata": ["Q7095133"]}
|
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (August 2011) (Learn how and when to remove this template message)
Skew deviation is an unusual ocular deviation (strabismus), wherein the eyes move upward (hypertropia), but in opposite directions. Skew deviation is caused by abnormal prenuclear vestibular input to the ocular motor nuclei, most commonly due to brainstem or cerebellar stroke. Other causes include multiple sclerosis and head trauma. Skew deviation is usually characterized by torticollis (head tilting) and binocular torsion. The exact pathophysiology of skew deviation remains incompletely understood. Skew deviation appears to be a perturbation of the ocular tilt reaction, which is itself probably a vestigial righting response used to keep fish and other lateral-eyed animals properly oriented.[1]
There are three types of skew deviations:
Type 1: Upward deviation of both eyes; sound-induced vestibular symptoms; both eyes show counterclockwise rotary upward rotation
Type 2: Hypertropia in one eye; dorsolateral medullary infarctions; excyclotropia in the ipsilateral eye; hypertropia in the contralateral eye
Type 3: Simultaneous hypertropia one eye and hypotropia in the other eye; upper brainstem lesion
Conway M (2013) Oculomotor disorders in the brainstem, Supranuclear palsies [City University London]
## References[edit]
1. ^ Brodsky, M; Donahue, S; Vaphiades, M; Brandt, T (2006). "Skew Deviation Revisited". Survey of Ophthalmology. 51 (2): 105–28. doi:10.1016/j.survophthal.2005.12.008. PMID 16500212.
## Further reading[edit]
This article lacks ISBNs for the books listed in it. Please make it easier to conduct research by listing ISBNs. If the {{Cite book}} or {{citation}} templates are in use, you may add ISBNs automatically, or discuss this issue on the talk page. (August 2011)
* Adams; Victor (1997). Principles of Neurology (6 ed.).[page needed]
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
|
Skew deviation
|
c0271381
| 7,535 |
wikipedia
|
https://en.wikipedia.org/wiki/Skew_deviation
| 2021-01-18T18:43:50 |
{"mesh": ["D015835"], "umls": ["C0271381"], "wikidata": ["Q1614766"]}
|
Dysmetria
SpecialtyNeurology
Dysmetria (English: wrong length) is a lack of coordination of movement typified by the undershoot or overshoot of intended position with the hand, arm, leg, or eye. It is a type of ataxia. It can also include an inability to judge distance or scale.[1]
Hypermetria and hypometria are, respectively, overshooting and undershooting the intended position.[2][3]
## Contents
* 1 Presentation
* 1.1 Associated diseases
* 2 Causes
* 3 Anatomy
* 3.1 Motor
* 3.2 Saccadic
* 4 Diagnosis
* 5 Treatments
* 5.1 Research
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
### Associated diseases[edit]
Dysmetria is often found in individuals with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and persons who have suffered from tumors or strokes. Persons who have been diagnosed with autosomal dominant spinocerebellar ataxia (SCAs) also exhibit dysmetria.[4] There are many types of SCAs and though many exhibit similar symptoms (one being dysmetria), they are considered to be heterogeneous.[4] Friedreich's ataxia is a well-known SCA in which children have dysmetria.[5] Cerebellar malformations extending to the brainstem can also present with dysmetria.[6]
## Causes[edit]
The actual cause of dysmetria is thought to be caused by lesions in the cerebellum or by lesions in the proprioceptive nerves that lead to the cerebellum that coordinate visual, spatial and other sensory information with motor control.[7] Damage to the proprioceptive nerves does not allow the cerebellum to accurately judge where the hand, arm, leg, or eye should move. These lesions are often caused by strokes, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or tumors.
According to the research article cited above, motor control is a learning process that utilizes APPGs.[8] Disruption of APPGs is possibly the cause of ataxia and dysmetria and upon identification of the motor primitives, clinicians may be able to isolate the specific areas responsible for the cerebellar problems.[8]
There are two types of cerebellar disorders that produce dysmetria, specifically midline cerebellar syndromes and hemispheric cerebellar syndromes. Midline cerebellar syndromes can cause ocular dysmetria, a condition in which the eyes can not track an object properly and either overshoot (ahead of the object )or undershoot (lagging behind the object). Ocular dysmetria also makes it difficult to maintain fixation on a stationary object. Hemispheric cerebellar syndromes cause dysmetria in the typical motor sense that many think of when hearing the term dysmetria.
A common motor syndrome that causes dysmetria is cerebellar motor syndrome, which also marked by impairments in gait (also known as ataxia), disordered eye movements, tremor, difficulty swallowing and poor articulation.[5] As stated above, cerebellar cognitive affective syndrome (CCAS) also causes dysmetria.
## Anatomy[edit]
The cerebellum is the area of the brain that contributes to coordination and motor processes and is anatomically inferior to the cerebrum.[9][7] Sensorimotor integration is the brain's way of integrating the information received from the sensory (or proprioceptive) neurons from the body, including any visual information. To be more specific, information needed to perform a motor task comes from retinal information pertaining to the eyes' position and has to be translated into spatial information. Sensorimotor integration is crucial for performing any motor task and takes place in the post parietal cortex.[9][10] After the visual information has been translated into spatial information, the cerebellum must use this information to perform the motor task.[5] If there is damage to any pathways that connect the pathways, dysmetria may result.
### Motor[edit]
Motor dysmetria is the customary term used when a person refers to dysmetria. Dysmetria of the extremities caused by hemispheric syndromes is manifested in multiple ways: dysrhythmic tapping of hands and feet and dysdiadochokinesis, which is the impairment of alternating movements.[5] Damage to the cerebellum makes a person slow to orient their extremities in space.[7]
Motor control as a learning process
Recent research has also shed light upon a specific process that if interrupted, may be the cause of ataxia and dysmetria. According to sources cited in this article, motor control is a learning process that occurs in the synapses of Purkinje dendrites.[8] There have been varying theories as to the makeup of the cerebellum, which controls this process. Some predicted that the cerebellum was an array of adjustable pattern generators (APGs), each of which generate a "burst command" with varying intensity and duration. Other models, which apply mostly in robotic applications, propose that the cerebellum acquires an "inverse model of the motor apparatus".[8] More recent research in electrophysiology has shown modular structures in the spinal cord known as "motor primitives".[8] Based on the APG model, modules of APG are the features that control motor learning.[8] The entire process is a positive feedback loop. Inhibitory input is transmitted and received from various components of the cortex, including the cerebellar nucleus, a motor cortical cell and Purkinje cells.[8] Purkinje cells send the inhibitive information by obtaining learning information from parallel fibers of granule cells. This model of APGs is useful in that it effectively describes the motor learning process.[8]
Motor primitives are another proposed module of motor learning.[8] This information was found by electrical stimulation of the lumbar spinal cord in rats and frogs.[8] Upon the stimulation, researchers found that motor primitives are found in the spinal cord and use patterns of muscle activation to generate a specific motor output. Different movements are learned from different levels of activation. These findings led researchers to believe that these same motor primitives could be found in the cerebellum.[8]
These two different models combined show that it is possible that motor primitives are in the cerebellum, because, "a set of parallel arrays of APG can drive each motor primitive module in the spinal cord."[8] The authors have generated a model of adjustable primitive pattern generator (APPG), which is basically a group of parallel APGs summed together.[8]
The APPG model is a vector sum of all the inputs of the APG, which are units of position, velocity and time.[8] Granule cells send information from the spinal cord and the motor cortex which in turn translates the information in a process called state mapping.[8] The final model of the APPG becomes linear upon the vector summation of the information from the neurons and muscles.[8] This model is consistent with the "virtual trajectory hypothesis" which states that the desired trajectory is sent to the spinal cord as a motor command.[8]
### Saccadic[edit]
Saccades are the very quick, simultaneous movements made by the eye to receive visual information and shift the line of vision from one position to another.[11] A person depends profoundly on the ability of the accuracy of these movements.[11] The information is received from the retina, is translated into spatial information and is then transferred to motor centers for motor response. A person with saccadic dysmetria will constantly produce abnormal eye movements including microsaccades, ocular flutter, and square wave jerks even when the eye is at rest.[5] During eye movements hypometric and hypermetric saccades will occur and interruption and slowing of normal saccadic movement is common.[5]
## Diagnosis[edit]
Diagnosis of any cerebellar disorder or syndrome should be made by a qualified neurologist. Prior to referring a patient to a neurologist, a general practitioner or MS nurse will perform a finger-to-nose test.[5] The clinician will raise a finger in front of the patient and ask him to touch it with his finger and then touch his nose with his forefinger several times. This shows a patient's ability to judge the position of a target. Other tests that could be performed are similar in nature and include a heel to shin test in which proximal overshoot characterizes dysmetria and an inability to draw an imaginary circle with the arms or legs without any decomposition of movement.[5] After a positive result in the finger-to-nose test, a neurologist will do a magnetic resonance image (MRI) to determine any damage to the cerebellum.[5]
Cerebellar patients encounter difficulties to adapt to unexpected changes of the inertia of the limbs.[12] This can be used to increase dysmetria and confirm a diagnosis of cerebellar dysfunction. Patients also show an abnormal response to changes in damping. These findings confirm a role of the cerebellum in predictions.[13]
## Treatments[edit]
Currently there is no cure for dysmetria itself as it is actually a symptom of an underlying disorder. However, isoniazid and clonazepam have been used to treat dysmetria. Frenkel exercises treat dysmetria.
### Research[edit]
Researchers now are testing different possibilities for treating dysmetria and ataxia. One opportunity for treatment is called rehearsal by eye movement.[14] It is believed that visually guided movements require both lower- and higher-order visual functioning by first identifying a target location and then moving to acquire what is sought after.[4] In one study, researchers used visually guided stepping which is parallel to visually guided arm movements to test this treatment.[14] The patients suffered from saccadic dysmetria which in turn caused them to overshoot their movements 3. The patients first walked normally and were then told to twice review the area that was to be walked through 3. After rehearsal with eye movements, the patients improved their motor performance.[14] Researchers believe that prior rehearsal with the eyes might be enough for a patient who suffers from motor dysmetria as a result of saccadic dysmetria to complete a motor task with enhanced spatial awareness.[14]
Research has also been done for those patients who suffer from MS.[15] Deep brain stimulation (DBS) remains a viable possibility for some MS patients though the long-term effects of this treatment are currently under review.[15] The subjects who have undergone this treatment had no major relapse for six months and disabling motor function problems.[15] Most subjects benefited from the implantation of the electrodes and some reported that their movement disorder was gone after surgery.[15] However, these results are limiting at this time because of the small range of subjects who were used for the experiment and it is unknown whether this is a viable option for all MS patients who suffer from motor control problems.[15]
## See also[edit]
* Intention tremor
* Ocular dysmetria
## References[edit]
1. ^ "dysmetria - definition of dysmetria in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia".
2. ^ Schmahmann JD, Weilburg JB, Sherman JC (2007). "The neuropsychiatry of the cerebellum - insights from the clinic". Cerebellum. 6 (3): 254–67. doi:10.1080/14734220701490995. PMID 17786822.
3. ^ Manto M (2009). "Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases". J Neuroeng Rehabil. 6: 10. doi:10.1186/1743-0003-6-10. PMC 2679756. PMID 19364396.
4. ^ a b c Manto MU (2005). "The wide spectrum of spinocerebellar ataxias (SCAs)". Cerebellum. 4 (1): 2–6. doi:10.1080/14734220510007914. PMID 15895552.
5. ^ a b c d e f g h i Schmahmann JD (2004). "Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome". J Neuropsychiatry Clin Neurosci. 16 (3): 367–78. doi:10.1176/jnp.16.3.367. PMID 15377747.
6. ^ Mario Manto (2010). Cerebellar Disorders: A Practical Approach to Diagnosis and Management. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-87813-5. OCLC 456170457.
7. ^ a b c Townsend J, Courchesne E, Covington J, et al. (July 1999). "Spatial attention deficits in patients with acquired or developmental cerebellar abnormality". J. Neurosci. 19 (13): 5632–43. doi:10.1523/JNEUROSCI.19-13-05632.1999. PMID 10377369.
8. ^ a b c d e f g h i j k l m n o p q Vahdat S, Maghsoudi A, Haji Hasani M, Towhidkhah F, Gharibzadeh S, Jahed M (October 2006). "Adjustable primitive pattern generator: a novel cerebellar model for reaching movements". Neurosci. Lett. 406 (3): 232–4. doi:10.1016/j.neulet.2006.07.038. PMID 16930835.
9. ^ a b Trillenberg P, Sprenger A, Petersen D, Kömpf D, Heide W, Helmchen C (2007). "Functional dissociation of saccade and hand reaching control with bilateral lesions of the medial wall of the intraparietal sulcus: implications for optic ataxia". NeuroImage. 36 Suppl 2: T69–76. doi:10.1016/j.neuroimage.2007.03.038. PMID 17499172.
10. ^ Indovina I, Sanes JN (October 2001). "Combined visual attention and finger movement effects on human brain representations". Exp Brain Res. 140 (3): 265–79. doi:10.1007/s002210100796. PMID 11681302.
11. ^ a b Iwamoto Y, Yoshida K (June 2002). "Saccadic dysmetria following inactivation of the primate fastigial oculomotor region". Neurosci. Lett. 325 (3): 211–5. doi:10.1016/S0304-3940(02)00268-9. PMID 12044658.
12. ^ Manto, M.; Godaux, E.; Jacquy, J. (January 1994). "Cerebellar hypermetria is larger when the inertial load is artificially increased". Annals of Neurology. 35 (1): 45–52. doi:10.1002/ana.410350108. ISSN 0364-5134. PMID 8285591.
13. ^ Leggio, M.; Molinari, M. (February 2015). "Cerebellar sequencing: a trick for predicting the future". Cerebellum (London, England). 14 (1): 35–38. doi:10.1007/s12311-014-0616-x. ISSN 1473-4230. PMID 25331541.
14. ^ a b c d Crowdy KA, Kaur-Mann D, Cooper HL, Mansfield AG, Offord JL, Marple-Horvat DE (September 2002). "Rehearsal by eye movement improves visuomotor performance in cerebellar patients". Exp Brain Res. 146 (2): 244–7. doi:10.1007/s00221-002-1171-0. PMID 12195526.
15. ^ a b c d e Hooper J, Taylor R, Pentland B, Whittle IR (April 2002). "A prospective study of thalamic deep brain stimulation for the treatment of movement disorders in multiple sclerosis". Br J Neurosurg. 16 (2): 102–9. doi:10.1080/02688690220131769. PMID 12046727.
## External links[edit]
Classification
D
* ICD-10: R27
* ICD-9-CM: 781.3
* MeSH: D002524
* DiseasesDB: 2218
* SNOMED CT: 32566006
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dysmetria
|
c0234162
| 7,536 |
wikipedia
|
https://en.wikipedia.org/wiki/Dysmetria
| 2021-01-18T18:35:03 |
{"mesh": ["D002524"], "icd-9": ["781.3"], "icd-10": ["R27"], "wikidata": ["Q517183"]}
|
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)
The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted.
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(Learn how and when to remove this template message)
Hybristophilia is a paraphilia in which sexual arousal, facilitation, and attainment of orgasm are responsive to and contingent upon being with a partner known to have committed a known crime, such as rape or murder. The term is derived from the Greek word hubrizein (ὑβρίζειν), meaning "to commit an outrage against someone" (ultimately derived from hubris ὕβρις, "hubris"), and philo, meaning "having a strong affinity/preference for".[1] In popular culture, this phenomenon is also known as "Bonnie and Clyde syndrome".[2]
Many high-profile criminals, particularly those who have committed atrocious crimes, receive "fan mail" in prison that is sometimes amorous or sexual, presumably as a result of this phenomenon. In some cases, admirers of these criminals have gone on to marry the object of their affections in prison.[3][4]
## Contents
* 1 Lexicology
* 2 Causes
* 3 Examples
* 4 References
* 5 Further reading
## Lexicology[edit]
The term is derived from the Greek word ὑβρίζειν hubrizein, meaning "to commit an outrage against someone" (ultimately derived from ὕβρις hubris "hubris"), and philo, meaning "having a strong affinity/preference for".[5] In popular culture, this phenomenon is also known as "Bonnie and Clyde Syndrome".[6] Women who write pen letters or even pursue men who are incarcerated for a crime are sometimes referred to as a prison groupie.[7][8] In its broadest sense, hybristophilia includes attraction towards partners who displayed dark triad personality traits.[9]
## Causes[edit]
Some speculations have been offered as to the cause of hybristophilia. For instance, Katherine Ramsland, who is a professor of forensic psychology at DeSales University mentions that some of the women in particular who have married or dated male serial killers have offered the following reasons:[citation needed]
* low self esteem and the lack of a father figure
* "Some believe they can change a man as cruel and powerful as a serial killer."
* "Others 'see' the little boy that the killer once was and seek to nurture him."
* "A few hoped to share in the media spotlight or get a book or movie deal."
* "Then there's the notion of the 'perfect boyfriend'. She knows where he is at all times and she knows he's thinking about her. While she can claim that someone loves her, she does not have to endure the day-to-day issues involved in most relationships. There’s no laundry to do, no cooking for him, and no accountability to him. She can keep the fantasy charged up for a long time."
Others offered reasons along the lines of:
* "Some mental health experts have compared infatuation with killers to extreme forms of fanaticism. They view such women as insecure females who cannot find love in normal ways or as 'love-avoidant' females who seek romantic relationships that cannot be consummated."[3]
Psychologist Leon F. Seltzer has offered explanations for the phenomenon of male serial killers attracting female sex partners based on evolutionary psychology. Serial killers, in his view, are cases of alpha males that tend to attract women. This is because such males were good at protecting women and their offspring according to evolutionary history. He says women today may consciously realize that it is unwise to date a serial killer, but they are nevertheless attracted to them; he stated, "as a therapist I've encountered many women who bemoaned their vulnerability toward dominant men who, consciously, they recognized were all wrong for them".[4] As evidence of women's fantasy preference for dominant men, he refers to the book A Billion Wicked Thoughts: What the World's Largest Experiment Reveals about Human Desire by Ogi Ogas and Sai Gaddam. Seltzer discusses Ogas and Gaddam's argument that this fantasy is the dominant plot of most erotic/romantic books and movies written for women but the fantasy always holds that this male dominance is conditional, "it doesn't really represent the man's innermost reality".[4]
## Examples[edit]
This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2016) (Learn how and when to remove this template message)
* One of the most infamous examples of hybristophilia is the large number of women attracted to Ted Bundy after his arrest.[10] He often drew scores of women at the jammed courtrooms of his trials each day.[11] Bundy allegedly received hundreds of love letters from women while he was incarcerated, and married a woman, Carole Ann Boone, who he had met while working in Washington. He proposed to her in the middle of proceedings while Boone was on the witness stand. Boone gave birth to a daughter who it was believed Bundy had fathered.[12][13]
* Jeffrey Dahmer, a serial killer, is said to have had amorous women sending him letters, money, and other gifts during his time in prison.[14]
* Serial killer Richard Ramirez married a prison groupie while in prison who had written him over 75 letters. During his trial, dozens of women flocked to the courtroom to catch a glimpse of him.
* Charles Manson's groupies are also examples.[15]
* Terrorists such as Anders Behring Breivik[16] and Dzhokhar Tsarnaev[17] have also been the objects of hybristophilia.
## References [edit]
1. ^ Eric W. Hickey, ed. (2006). Sex crimes and paraphilia. Upper Saddle River, N.J.: Pearson Education. pp. 197–9. ISBN 9780131703506.
2. ^ "Bonnie and Clyde Syndrome Is a Real Thing - Nerve". Internet Archive. Archived from the original on 2017-11-13.
3. ^ a b Ramsland, Katherine (20 April 2012). "Women Who Love Serial Killers". Psychology Today. Retrieved 13 May 2013.
4. ^ a b c Seltzer, Leon F. (24 April 2012). "Why Do Women Fall for Serial Killers?". Psychology Today. Retrieved 13 May 2013.
5. ^ Eric W. Hickey, ed. (2006). Sex crimes and paraphilia. Upper Saddle River, N.J.: Pearson Education. pp. 197–9. ISBN 9780131703506.
6. ^ "Bonnie and Clyde Syndrome Is a Real Thing - Nerve". Internet Archive. Archived from the original on 2017-11-13.
7. ^ https://www.nytimes.com/2018/04/02/arts/television/the-last-og-review-tracy-morgan-tbs.html
8. ^ Mailhot, Terese. "Paul Simon Money." Transmotion 2.1&2 (2016): 131.
9. ^ Watts, Ashley L., et al. "Do Psychopathic Birds of a Feather Flock Together? Psychopathic Personality Traits and Romantic Preferences." Journal of personality (2018).
10. ^ Cawthorne, Nigel (2007). Serial Killers and Mass Murderers: Profiles of the World's Most Barbaric Criminals. Ulysses Press.
11. ^ Michaud, Stephen G. "The Only Living Witness: The True Story Of Ted Bundy". Crime Library.
12. ^ "Bundy's wife is pregnant – but she refuses to kiss, tell". Deseret News. Salt Lake City, Utah: Deseret News Publishing Company. Associated Press. September 30, 1981. Retrieved April 25, 2011.
13. ^ Levenson, Bob (January 24, 1989). "Courtroom Wife Fades Out of Sight, Not A Recent Visitor". Orlando Sentinel.
14. ^ Barnard, Ian; Nanny M. W. de Vries, Jan Best. "The Racialization of Sexuality: The Queer Case of Jeffrey Dahmer". Thamyris Overcoming Boundaries: Ethnicity, Gender and Sexuality. Thamyris Intersecting. Rodopi. p. 88. ISSN 1381-1312.
15. ^ Corsini, Raymond Joseph (1999). The Dictionary of Psychology. Psychology Press. p. 692. ISBN 1-58391-028-X.
16. ^ "Breivik 'gets love letters from 16-year-old girls'". The Local. June 18, 2012.
17. ^ Allen, Charlotte (May 22, 2013). "Dzhokhar Tsarnaev and his fangirls". Los Angeles Times.
## Further reading[edit]
* Sheila Isenberg: Women Who Love Men Who Kill, third edition, Backinprint.com 2000, ISBN 978-0-595-00399-0
* Jacquelynne Willcox-Bailey: Dream Lovers: Women Who Marry Men Behind Bars, Wakefield Press 1999, ISBN 978-1-86254-381-2
* Why are women drawn to men behind bars?, The Guardian, Monday 13 January 2003
* Women who have killer instincts, The Independent, 27 January 2005
* Liz O'Keefe: The partners of prisoners: Their reality, how they contribute to the criminal justice system and prisoner rehabilitation and how we can assist (PDF), paper presented at the Women in Corrections: Staff and Clients conference convened by the Australian Institute of Criminology in conjunction with the Department for Correctional Services South Australia, 31 October-1 November 2000, Adelaide, Australia
* v
* t
* e
Paraphilias
List
* Abasiophilia
* Acrotomophilia
* Agalmatophilia
* Algolagnia
* Apotemnophilia
* Autassassinophilia
* Biastophilia
* Capnolagnia
* Chremastistophilia
* Chronophilia
* Coprophagia
* Coprophilia
* Crurophilia
* Crush fetish
* Dacryphilia
* Dendrophilia
* Emetophilia
* Eproctophilia
* Erotic asphyxiation
* Erotic hypnosis
* Erotophonophilia
* Exhibitionism
* Formicophilia
* Frotteurism
* Gerontophilia
* Homeovestism
* Hybristophilia
* Infantophilia
* Kleptolagnia
* Klismaphilia
* Lactaphilia
* Macrophilia
* Masochism
* Mechanophilia
* Microphilia
* Narratophilia
* Nasophilia
* Necrophilia
* Object sexuality
* Odaxelagnia
* Olfactophilia
* Omorashi
* Paraphilic infantilism
* Partialism
* Pedophilia
* Podophilia
* Plushophilia
* Pyrophilia
* Sadism
* Salirophilia
* Scopophilia
* Somnophilia
* Sthenolagnia
* Tamakeri
* Telephone scatologia
* Transvestic fetishism
* Trichophilia
* Troilism
* Urolagnia
* Urophagia
* Vorarephilia
* Voyeurism
* Zoophilia
* Zoosadism
See also
* Other specified paraphilic disorder
* Erotic target location error
* Courtship disorder
* Polymorphous perversity
* Sexual fetishism
* Human sexual activity
* Perversion
* Sexology
* Book
* Category
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hybristophilia
|
None
| 7,537 |
wikipedia
|
https://en.wikipedia.org/wiki/Hybristophilia
| 2021-01-18T18:40:55 |
{"wikidata": ["Q1269190"]}
|
A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-9 (CORD9) is caused by homozygous or compound heterozygous mutation in the ADAM9 gene (602713) on chromosome 8p11.
For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970.
Clinical Features
Danciger et al. (2001) described a consanguineous Brazilian family segregating autosomal recessive CORD. Affected family members had childhood-onset visual acuity impairment, which progressed over decades to major loss of central and then peripheral visual function. In the 2 adult family members tested, visual acuity was 20/200 with a preserved midperipheral crescent on visual field testing. Refractive error was modest myopia with astigmatism. Small posterior subcapsular cataracts were present.
Parry et al. (2009) studied 3 additional consanguineous families segregating CORD9. One was of Pakistani origin, 1 Tunisian Jewish, and the other Arab Muslim. Affected individuals in these families reported poor visual acuity in the first decade of life, but nystagmus and photophobia were not noted. Outer retinal atrophy was observed in the macula. Most patients had discrete white patches in the posterior pole and around the optic disc with a pigmentary retinopathy, anterior to the equator. The midperipheral retina showed minimal changes on clinical exam of young patients, and older patients peripheral pigmentary changes could be observed in some cases. Electroretinograms (ERGs) showed a similar degree of rod and cone involvement.
El-Haig et al. (2014) described a consanguineous Egyptian family in which a mother and 2 of her children had cone-rod dystrophy characterized by childhood-onset visual loss, reorganization of the retinal pigment epithelium with midperipheral grayish-white discoloration, attenuated retinal vasculature, and optic disc pallor. The mother also had bilateral anterior polar and posterior subcapsular cataracts and 1 of the children had a coloboma-like macular lesion. Bilateral dot cataract was diagnosed in 3 of her other 4 children, who did not have CORD, 1 of whom also had glaucoma.
Mapping
By 4-point linkage analysis in the large Brazilian family segregating autosomal recessive CORD, Danciger et al. (2001) obtained a maximum lod score of approximately 7.6 at both D8S1769 and GATA101H09. Recombination events defined a critical interval of 8.7 cM between D8S1820 and D8S532. The 8p11 locus, designated CORD9, was immediately distal to but distinct from the RP1 gene (603937).
Parry et al. (2009) refined the CORD9 locus to a 2.95-Mb homozygous segment between SNPs rs10955025 and rs725401 containing 34 genes.
Molecular Genetics
In 4 consanguineous families with cone-rod dystrophy linked to the CORD9 locus, including the family reported by Danciger et al. (2001), Parry et al. (2009) identified 4 different mutations in the ADAM9 gene (602713.0001-602713.0004).
In a consanguineous Egyptian family with autosomal recessive cone-rod dystrophy, El-Haig et al. (2014) identified a splice site mutation in intron 13 of the ADAM9 gene (602713.0005); the mother and 2 children were homozygous for the mutation, while the unaffected father and 4 unaffected children were heterozygous.
### Exclusion Studies
In a Brazilian family segregating CORD9, Danciger et al. (2001) screened the exons of a dual specificity phosphatase gene (DUSP4; 602747), which maps in the CORD9 region, but identified no disease-causing mutations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CONE-ROD DYSTROPHY 9
|
c3489532
| 7,538 |
omim
|
https://www.omim.org/entry/612775
| 2019-09-22T16:00:40 |
{"doid": ["0111020"], "mesh": ["D000071700"], "omim": ["120970", "612775"], "orphanet": ["1872"], "synonyms": []}
|
## Clinical Features
Congenital ocular fibrosis syndrome is a hereditary ocular motility disorder in which restrictive ophthalmoplegia and blepharoptosis are associated with replacement of orbital striated muscle by fibrous tissue (see CFEOM1; 135700). Brodsky et al. (1989) reported a child with congenital ocular fibrosis and oculocutaneous hypopigmentation who also manifested 2 neural misdirection syndromes: synergistic divergence and Marcus Gunn jaw winking. The authors hypothesized that a primary developmental defect involving the establishment of normal neuronal connections might be responsible for this congenital fibrosis syndrome.
Brodsky (1998) reported 3 patients, including the patient reported by Brodsky et al. (1989), who had congenital fibrosis syndrome and a variant of synergistic divergence characterized by simultaneous abduction with intorsion and depression of the synkinetically abducting eye. These patients had a variant of Marcus Gunn jaw winking characterized by elevation of a ptotic eyelid during mouth opening. All 3 patients also had exotropia with their eyes fixed in downgaze, and they showed oculocutaneous hypopigmentation. The mother of one patient was reported to be affected but was unavailable for examination, whereas the mother of another patient was affected and described. Brodsky (1998) concluded that the patterns of neuronal misdirection implicated a regional innervational disturbance involving cranial nerves III through VI as the underlying case of diffuse hereditary ophthalmoplegia in these patients.
Kim and Hwang (2005) described the neuropathologic findings in 2 patients with congenital fibrosis and synergistic divergence using magnetic resonance imaging (MRI). MRI showed bilateral hypoplasia of the oculomotor nerve and absence of the abducens nerve on the affected side of synergistic divergence. The oculomotor and abducens nerves were observed in 80 of 80 control eyes.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Backward head tilt Eyes \- Downward gaze \- Exotropia \- Ptosis \- Restricted eye movement \- Extraocular muscle fibrosis \- Marcus Gunn jaw winking (in some patients) \- Oculocutaneous hypopigmentation (in some patients) \- Hypoplastic oculomotor nerves, bilateral \- Absent abducens nerve on the affected side of synergistic divergence ▲ 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
|
FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, WITH SYNERGISTIC DIVERGENCE
|
c1302995
| 7,539 |
omim
|
https://www.omim.org/entry/609612
| 2019-09-22T16:05:48 |
{"mesh": ["C580012"], "omim": ["609612"], "orphanet": ["45358"], "synonyms": ["Alternative titles", "CONGENITAL FIBROSIS SYNDROME WITH SYNERGISTIC DIVERGENCE", "EXTERNAL OPHTHALMOPLEGIA WITH SYNERGISTIC DIVERGENCE"]}
|
Not to be confused with Guillain–Barré syndrome.
Gilbert's syndrome
Other namesMeulengracht syndrome, Gilbert-Lereboullet syndrome, hyperbilirubinemia Arias type, hyperbilirubinemia type 1, familial cholemia, familial nonhemolytic jaundice[1][2]
Bilirubin
Pronunciation
* /ʒiːlˈbɛərz/ zheel-BAIRZ
SpecialtyGastroenterology
SymptomsStrong abdominal pain, nausea, tired and weak feeling, slight jaundice[1]
ComplicationsUsually none[1]
CausesGenetic[1]
Differential diagnosisCrigler–Najjar syndrome, Rotor syndrome, Dubin–Johnson syndrome[2]
TreatmentNone typically needed[1]
Frequency~5%[3]
Gilbert's syndrome (GS) is a mild liver disorder in which the liver does not properly process bilirubin.[1] Many people never have symptoms.[1] Occasionally a slight yellowish color of the skin or whites of the eyes may occur.[1] Other possible symptoms include feeling tired, weakness, and abdominal pain.[1]
Gilbert's syndrome is due to a mutation in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme.[1][3] It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of mutation.[3] Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating.[3] Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.[2][3]
Typically no treatment is needed.[1] If jaundice is significant phenobarbital may be used.[1] Gilbert's syndrome affects about 5% of people in the United States.[3] Males are more often diagnosed than females.[1] It is often not noticed until late childhood to early adulthood.[2] The condition was first described in 1901 by Augustin Nicolas Gilbert.[2][4]
## Contents
* 1 Signs and symptoms
* 1.1 Jaundice
* 1.2 Detoxification of certain drugs
* 1.3 Cardiovascular effects
* 1.4 Other
* 2 Genetics
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 History
* 6 Notable cases
* 7 References
* 8 External links
## Signs and symptoms[edit]
### Jaundice[edit]
Gilbert's syndrome produces an elevated level of unconjugated bilirubin in the bloodstream, but normally has no serious consequences. Mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic.[5][6] Severe cases are seen by yellowing of the skin tone and yellowing of the sclera in the eye.[citation needed]
Gilbert's syndrome has been reported to contribute to an accelerated onset of neonatal jaundice. The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors,[7] for example in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency.[8][9] This situation can be especially dangerous if not quickly treated, as the high bilirubin causes irreversible neurological disability in the form of kernicterus.[10][11][12]
### Detoxification of certain drugs[edit]
The enzymes that are defective in GS – UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) – are also responsible for some of the liver's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.[13]
While paracetamol (acetaminophen) is not metabolized by UGT1A1,[14] it is metabolized by one of the other enzymes also deficient in some people with GS.[15][16] A subset of people with GS may have an increased risk of paracetamol toxicity.[16][17]
### Cardiovascular effects[edit]
Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS.[18][19]
Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease.[20] These researchers went on to perform a meta-analysis of data available up to 2002, and confirmed the incidence of atherosclerotic disease (hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin.[18] This beneficial effect was attributed to bilirubin IXα which is recognized as a potent antioxidant, rather than confounding factors such as high-density lipoprotein levels.[20]
This association was also seen in long-term data from the Framingham Heart Study.[21][22][non-primary source needed] Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype were associated with one-third the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, nonmutated gene locus).[citation needed]
Platelet counts and MPV are decreased in patients with Gilbert's syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the atherosclerotic process.[23]
### Other[edit]
Symptoms, whether connected or not to GS, have been reported in a subset of those affected: feeling tired all the time (fatigue), difficulty maintaining concentration, unusual patterns of anxiety, loss of appetite, nausea, abdominal pain, loss of weight, itching (with no rash), and others,[24] such as humor change or depression. But scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults. However, other substances glucuronidized by the affected enzymes in Gilbert's syndrome sufferers could theoretically, at their toxic levels, cause these symptoms.[25][26] Consequently, debate exists about whether GS should be classified as a disease.[25][27] However, Gilbert's syndrome has been linked to an increased risk of gallstones.[24][28]
## Genetics[edit]
Gilbert's syndrome is a phenotypic effect, mostly clearly associated with increased blood bilirubin levels, but also sometimes characterized by mild jaundice due to increased unconjugated bilirubin, that arises from several different genotypic variants of the gene for the enzyme responsible for changing bilirubin to the conjugated form.[citation needed]
Gilbert's syndrome is characterized by a 70–80% reduction in the glucuronidation activity of the enzyme (UGT1A1). The UGT1A1 gene is located on human chromosome 2.[29]
More than 100 variants of the UGT1A1 gene are known, designated as UGT1A1*n (where n is the general chronological order of discovery), either of the gene itself or of its promoter region. UGT1A1 is associated with a TATA box promoter region; this region most commonly contains the genetic sequence A(TA)6TAA; this variant accounts for about 50% of alleles in many populations. However, several allelic polymorphic variants of this region occur, the most common of which results from adding another dinucleotide repeat TA to the promoter region, resulting in A(TA)7TAA, which is called UGT1A1*28; this common variant accounts for about 40% of alleles in some populations, but is seen less often, around 3% of alleles, in Southeast and East Asian people and Pacific Islanders.[citation needed]
In most populations, Gilbert's syndrome is most commonly associated with homozygous A(TA)7TAA alleles.[30][31][32] In 94% of GS cases, two other glucuronosyltransferase enzymes, UGT1A6 (rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected.[citation needed]
However, Gilbert's syndrome can arise without TATA box promoter polymorphic mutations; in some populations, particularly healthy Southeast and East Asians, Gilbert's syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region,[17] which may be associated with significantly higher bilirubin levels.[17]
Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilbert's syndrome can be classed as a minor inborn error of metabolism.[citation needed]
## Diagnosis[edit]
People with GS predominantly have elevated unconjugated bilirubin, while conjugated bilirubin is usually within the normal range and is less than 20% of the total. Levels of bilirubin in GS patients are reported to be from 20 μM to 90 μM (1.2 to 5.3 mg/dl)[31] compared to the normal amount of < 20 μM. GS patients have a ratio of unconjugated/conjugated (indirect/direct) bilirubin commensurately higher than those without GS.[citation needed]
The level of total bilirubin is often further increased if the blood sample is taken after fasting for two days,[33] and a fast can, therefore, be useful diagnostically. A further conceptual step that is rarely necessary or appropriate is to give a low dose of phenobarbital:[34] the bilirubin will decrease substantially.
Tests can also detect DNA mutations of UGT1A1 by polymerase chain reaction or DNA fragment sequencing.[citation needed]
### Differential diagnosis[edit]
While Gilbert's syndrome is considered harmless, it is clinically important because it may give rise to a concern about a blood or liver condition, which could be more dangerous. However, these conditions have additional indicators:[citation needed]
* Hemolysis can be excluded by a full blood count, haptoglobin, lactate dehydrogenase levels, and the absence of reticulocytosis (elevated reticulocytes in the blood would usually be observed in haemolytic anaemia).[citation needed]
* Viral hepatitis can be excluded by negative blood samples for antigens specific to the different hepatitis viruses.[citation needed]
* Cholestasis can be excluded by normal levels of bile acids in plasma, the absence of lactate dehydrogenase, low levels of conjugated bilirubin, and ultrasound scan of the bile ducts.[citation needed]
* More severe types of glucuronyl transferase disorders such as Crigler–Najjar syndrome (types I and II) are much more severe, with 0–10% UGT1A1 activity, with sufferers at risk of brain damage in infancy (type I) and teenage years (type II).[citation needed]
* Dubin–Johnson syndrome and Rotor syndrome are rarer autosomal recessive disorders characterized by an increase of conjugated bilirubin.
* In GS, unless another disease of the liver is also present, the liver enzymes ALT/SGPT and AST/SGOT, as well as albumin, are within normal ranges.[citation needed]
## Treatment[edit]
Typically no treatment is needed.[1] If jaundice is significant phenobarbital may be used.[1]
## History[edit]
Gilbert's syndrome was first described by French gastroenterologist Augustin Nicolas Gilbert and co-workers in 1901.[4][35] In German literature, it is commonly associated with Jens Einar Meulengracht.[36]
Alternative, less common names for this disorder include:[citation needed]
* Familial benign unconjugated hyperbilirubinaemia
* Constitutional liver dysfunction
* Familial non-hemolytic non-obstructive jaundice
* Icterus intermittens juvenilis
* Low-grade chronic hyperbilirubinemia
* Unconjugated benign bilirubinemia
## Notable cases[edit]
* Napoleon I of France[37]
* Arthur Kornberg, Nobel laureate in Physiology or Medicine, 1959[38]
* Nicky Wire, Manic Street Preachers bassist[39]
* Alexandr Dolgopolov (tennis player)[40]
* Jonas Folger, MotoGP rider[41]
## References[edit]
1. ^ a b c d e f g h i j k l m n o "Gilbert syndrome". GARD. 2016. Archived from the original on 4 August 2017. Retrieved 2 July 2017.
2. ^ a b c d e "Gilbert Syndrome". NORD (National Organization for Rare Disorders). 2015. Archived from the original on 20 February 2017. Retrieved 2 July 2017.
3. ^ a b c d e f "Gilbert syndrome". Genetics Home Reference. 27 June 2017. Archived from the original on 27 June 2017. Retrieved 2 July 2017.
4. ^ a b "Whonamedit – dictionary of medical eponyms". www.whonamedit.com. Archived from the original on 18 September 2016. Retrieved 2 July 2017.
5. ^ Kasper et al., Harrison's Principles of Internal Medicine, 16th edition, McGraw-Hill 2005
6. ^ Boon et al., Davidson's Principles & Practice of Medicine, 20th edition, Churchill Livingstone 2006
7. ^ Saki, F.; Hemmati, F.; Haghighat, M. (2011). "Prevalence of Gilbert syndrome in parents of neonates with pathologic indirect hyperbilirubinemia". Annals of Saudi Medicine. 31 (2): 140–4. doi:10.4103/0256-4947.77498. PMC 3102472. PMID 21403409.
8. ^ Bancroft JD, Kreamer B, Gourley GR (1998). "Gilbert syndrome accelerates development of neonatal jaundice". Journal of Pediatrics. 132 (4): 656–60. doi:10.1016/S0022-3476(98)70356-7. PMID 9580766.
9. ^ Cappellini MD, Di Montemuros FM, Sampietro M, Tavazzi D, Fiorelli G (1999). "The interaction between Gilbert's syndrome and G6PD deficiency influences bilirubin levels". British Journal of Haematology. 104 (4): 928–9. doi:10.1111/j.1365-2141.1999.1331a.x. PMID 10192462. S2CID 40300539.
10. ^ "Acute bilirubin encephalopathy and its progression to kernicterus: current perspectives".
11. ^ "Learning from claims: hyperbilirubinaemia and kernicterus".
12. ^ "Kernicterus".
13. ^ Marcuello E, Altés A, Menoyo A, Del Rio E, Gómez-Pardo M, Baiget M (2004). "UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer". Br J Cancer. 91 (4): 678–82. doi:10.1038/sj.bjc.6602042. PMC 2364770. PMID 15280927.
14. ^ Rauchschwalbe S, Zuhlsdorf M, Wensing G, Kuhlmann J (2004). "Glucuronidation of acetaminophen is independent of UGT1A1 promotor genotype". Int J Clin Pharmacol Ther. 42 (2): 73–7. doi:10.5414/cpp42073. PMID 15180166.
15. ^ Kohle C, Mohrle B, Munzel PA, Schwab M, Wernet D, Badary OA, Bock KW (2003). "Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians". Biochem Pharmacol. 65 (9): 1521–7. doi:10.1016/S0006-2952(03)00074-1. PMID 12732365.
16. ^ a b Esteban A, Pérez-Mateo M (1999). "Heterogeneity of paracetamol metabolism in Gilbert's syndrome". European Journal of Drug Metabolism and Pharmacokinetics. 24 (1): 9–13. doi:10.1007/BF03190005. PMID 10412886. S2CID 27543027.
17. ^ a b c Gilbert Syndrome at eMedicine
18. ^ a b Ladislav Novotnýc; Libor Vítek (2003). "Inverse Relationship Between Serum Bilirubin and Atherosclerosis in Men: A Meta-Analysis of Published Studies". Experimental Biology and Medicine. 228 (5): 568–571. doi:10.1177/15353702-0322805-29. PMID 12709588. S2CID 43486067.
19. ^ Schwertner Harvey A; Vítek Libor (May 2008). "Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin". Atherosclerosis (Review). 198 (1): 1–11. doi:10.1016/j.atherosclerosis.2008.01.001. PMID 18343383.
20. ^ a b Vítek L; Jirsa M; Brodanová M; et al. (2002). "Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels". Atherosclerosis. 160 (2): 449–56. doi:10.1016/S0021-9150(01)00601-3. PMID 11849670.
21. ^ Lin JP; O’Donnell CJ; Schwaiger JP; et al. (2006). "Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study". Circulation. 114 (14): 1476–81. doi:10.1161/CIRCULATIONAHA.106.633206. PMID 17000907.
22. ^ Bulmer, A. C.; Verkade, H. J.; Wagner, K.-H. (April 2013). "Bilirubin and beyond: a review of lipid status in Gilbert's syndrome and its relevance to cardiovascular disease protection". Progress in Lipid Research. 52 (2): 193–205. doi:10.1016/j.plipres.2012.11.001. hdl:10072/54228. ISSN 1873-2194. PMID 23201182.
23. ^ Kundur, Avinash R.; Singh, Indu; Bulmer, Andrew C. (March 2015). "Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?". Atherosclerosis. 239 (1): 73–84. doi:10.1016/j.atherosclerosis.2014.12.042. ISSN 1879-1484. PMID 25576848.
24. ^ a b GilbertsSyndrome.com Archived 2006-08-10 at the Wayback Machine
25. ^ a b Olsson R, Bliding A, Jagenburg R, Lapidus L, Larsson B, Svärdsudd K, Wittboldt S (1988). "Gilbert's syndrome—does it exist? A study of the prevalence of symptoms in Gilbert's syndrome". Acta Medica Scandinavica. 224 (5): 485–490. doi:10.1111/j.0954-6820.1988.tb19615.x. PMID 3264448.
26. ^ Bailey A, Robinson D, Dawson AM (1977). "Does Gilbert's disease exist?". Lancet. 1 (8018): 931–3. doi:10.1016/S0140-6736(77)92226-7. PMID 67389. S2CID 41989158.
27. ^ Larissa K. F. Temple; Robin S. McLeod; Steven Gallinger; James G. Wright (2001). "Defining Disease in the Genomics Era". Science Magazine. 293 (5531): 807–808. doi:10.1126/science.1062938. PMID 11486074.
28. ^ del Giudice EM, Perrotta S, Nobili B, Specchia C, d'Urzo G, Iolascon A (October 1999). "Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis". Blood. 94 (7): 2259–62. doi:10.1182/blood.V94.7.2259.419k42_2259_2262. PMID 10498597. Archived from the original on 2013-04-14.
29. ^ "Entrez Gene: UGT1A1 UDP glucuronosyltransferase 1 family, polypeptide A1". Archived from the original on 2010-12-05.
30. ^ Raijmakers MT, Jansen PL, Steegers EA, Peters WH (2000). "Association of human liver bilirubin UDP-glucuronyltransferase activity, most commonly due to a polymorphism in the promoter region of the UGT1A1 gene". Journal of Hepatology. 33 (3): 348–351. doi:10.1016/S0168-8278(00)80268-8. PMID 11019988.
31. ^ a b Bosma PJ; Chowdhury JR; Bakker C; Gantla S; de Boer A; Oostra BA; Lindhout D; Tytgat GN; Jansen PL; Oude Elferink RP; et al. (1995). "The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome". New England Journal of Medicine. 333 (18): 1171–5. doi:10.1056/NEJM199511023331802. PMID 7565971.
32. ^ Monaghan G, Ryan M, Seddon R, Hume R, Burchell B (1996). "Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome". Lancet. 347 (9001): 578–81. doi:10.1016/S0140-6736(96)91273-8. PMID 8596320. S2CID 24943762.
33. ^ J L Gollan; C Bateman; B H Billing (1976). "Effect of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome". Gut. 17 (5): 335–340. doi:10.1136/gut.17.5.335. PMC 1411132. PMID 1278716.
34. ^ N Carulli; M Ponz de Leon; E Mauro; F Manenti; A Ferrari (1976). "Alteration of drug metabolism in Gilbert's syndrome". Gut. 17 (8): 581–587. doi:10.1136/gut.17.8.581. PMC 1411334. PMID 976795.
35. ^ Gilbert A, Lereboullet P (1901). "La cholémie simple familiale". La Semaine Médicale. 21: 241–3.
36. ^ Jens Einar Meulengracht at Who Named It?
37. ^ Foulk, WT; Butt, HR; Owen, CA Jr; Whitcomb, FF Jr; Mason, HL (1959). "Constitutional hepatic dysfunction (Gilbert's disease): its natural history and related syndromes". Medicine (Baltimore). 38 (1): 25–46. doi:10.1097/00005792-195902000-00002. PMID 13632313. S2CID 8265932.
38. ^ Shmaefsky, Brian (2006). "5". Biotechnology 101. Greenwood Publishing Group. pp. 175. ISBN 978-0-313-33528-0.
39. ^ "Wire preaches delights of three cliffs". South Wales Evening Post. 2007-04-27. p. 3.
40. ^ David Cox. (19 April 2014). "A Tennis Player Learns to Be Aggressive for Health's Sake". New York Times. Monte Carlo. Archived from the original on 14 October 2016.
41. ^ Khorounzhiy, Valentin (2017-11-09). "Illness that 'shut down' Tech3 MotoGP rookie Jonas Folger diagnosed". Autosport.com. Motorsport Network. Retrieved 2017-11-09. "After visiting specialists in his native Germany, Folger has been diagnosed with Gilbert's syndrome – a genetic ailment that precludes the liver from correctly processing bilirubin."
## External links[edit]
* https://gilbertssyndrome.org.uk
* Gilbert's syndrome at NIH's Office of Rare Diseases
* Gilbert's Syndrome BMJ Best Practices monograph
Classification
D
* ICD-10: E80.4
* ICD-9-CM: 277.4
* OMIM: 143500
* MeSH: D005878
* DiseasesDB: 5218
* SNOMED CT: 27503000
External resources
* MedlinePlus: 000301
* eMedicine: med/870
* Patient UK: Gilbert's syndrome
* v
* t
* e
Heme metabolism disorders
Porphyria,
hepatic and erythropoietic
(porphyrin)
early mitochondrial:
* ALAD porphyria
* Acute intermittent porphyria
cytoplasmic:
* Gunther disease/congenital erythropoietic porphyria
* Porphyria cutanea tarda/Hepatoerythropoietic porphyria
late mitochondrial:
* Hereditary coproporphyria
* Harderoporphyria
* Variegate porphyria
* Erythropoietic protoporphyria
Hereditary hyperbilirubinemia
(bilirubin)
unconjugated:
* Gilbert's syndrome
* Crigler–Najjar syndrome
* Lucey–Driscoll syndrome
conjugated:
* Dubin–Johnson syndrome nd sheet
* Rotor 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
|
Gilbert's syndrome
|
c0017551
| 7,540 |
wikipedia
|
https://en.wikipedia.org/wiki/Gilbert%27s_syndrome
| 2021-01-18T18:43:41 |
{"gard": ["6507"], "mesh": ["D005878"], "umls": ["C0017551"], "icd-9": ["277.4"], "icd-10": ["E80.4"], "orphanet": ["357"], "wikidata": ["Q752216"]}
|
A number sign (#) is used with this entry because variation in the GOT1 gene (138180) results in low serum glutamate oxaloacetate transaminase, also known as aspartate aminotransferase (AST).
Mapping
Shen et al. (2011) carried out a genomewide association study of serum AST (EC 2.6.1.1) activity in 866 Amish participants of the Heredity and Phenotype Intervention Heart Study and identified a significant association of AST activity with a cluster of SNPs located on chromosome 10q24 (peak association was rs17109512; p = 2.80 x 10(-14)), in the vicinity of the GOT1 gene, which encodes cytosolic AST. The 10 subjects heterozygous for the associated SNP had significantly lower AST levels compared with the 856 homozygotes for the wildtype allele.
Molecular Genetics
Given the low frequency of the associated SNP, its proximity to GOT1, and the very large effect size of the association, Shen et al. (2011) hypothesized that rs17109512 might tag a functional SNP in GOT1. Sequencing of GOT1 revealed an in-frame deletion of 3 nucleic acids encoding asparagine at position 389 (138180.0001). The deletion was in complete linkage with rs17109512. Deletion carriers had significantly lower AST activity levels compared with homozygotes for deletion noncarriers (mean +/- SD: 10.0 +/- 2.8 vs 18.8 +/- 5.2 microliter; p = 2.80 x 10(-14)). Further genotyping of the deletion in 1,932 other Amish samples identified an additional 20 carriers (minor allele frequency = 0.0052). The deletion was not detected in 647 outbred Caucasians. Asparagine at codon 389 is conserved among known mammalian cytoplasmic ASTs (cASTs). In vitro transient transfection assays of wildtype and mutant cAST indicated that mutant cAST protein was barely detectable in the cells. Furthermore, even after correction for cAST expression, mutant cAST had markedly diminished enzymatic activity. Remarkably, there was no association between the deletion and metabolic traits including serum fasting glucose or insulin, fasting and postmeal lipids, inflammatory markers, or subclinical markers of cardiovascular disease.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ASPARTATE AMINOTRANSFERASE, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 1
|
c3280741
| 7,541 |
omim
|
https://www.omim.org/entry/614419
| 2019-09-22T15:55:20 |
{"omim": ["614419"], "synonyms": ["Alternative titles", "ASTQTL1"]}
|
Canine cognitive dysfunction (CCD) is a disease prevalent in dogs that exhibit symptoms of dementia or Alzheimer's disease shown in humans.[1] CCD creates pathological changes in the brain that slow the mental functioning of dogs resulting in loss of memory, motor function, and learned behaviors from training early in life. In the dog's brain, the protein beta-amyloid accumulates, creating protein deposits called plaques. As the dog ages, nerve cells die, and cerebrospinal fluid fills the empty space left by the dead nerve cells.[2] Canine cognitive dysfunction takes effect in older dogs, mostly after 10 years of age. Although there is no known cause of CCD, genetic factors have been shown to contribute to the occurrence of this disease.[3]
## Contents
* 1 Clinical signs
* 2 Diagnosis
* 3 Treatment
* 4 Precautions
* 5 See also
* 6 References
## Clinical signs[edit]
Dogs with canine cognitive dysfunction may exhibit many symptoms associated with senile behavior and dementia. Dogs will often find themselves confused in familiar places of the home, spending long periods of time in one area of the home, not responding to calls or commands, and experiencing abnormal sleeping patterns.[4] Although some of these symptoms may be attributed to old age itself, when they are exhibited together, there is a higher likelihood of CCD.
## Diagnosis[edit]
In order to properly diagnose CCD in dogs, there is a list of symptoms that when observed together, show signs of the disease.[2]
* Disorientation – loss of ability to navigate the house or remember where specific places are (i.e. furniture, corners of rooms)
* Interaction changes – decreased interest in social interaction (i.e. petting, grooming, playing)
* Sleep/wake cycle Changes – restlessness throughout the night, sleeping during the day
* Housebreaking issues – defecating indoors, not signaling to go outside
* Physical activity level – decreased interest in being outside, decreased responses to stimuli (e.g. sounds around home, people)
Any medical causes for these symptoms must be ruled out. Medical diagnoses that may contribute to these symptoms include thyroid disorders, Cushing's disease, diabetes, kidney disease, musculoskeletal disease, cancer, liver problems, and sensory loss. Also, behavioral problems in dogs may be factors that influence these symptoms (i.e. lack of housetraining, lack of social interaction, separation anxiety, phobias, aggression and compulsive disorders).
## Treatment[edit]
There is no cure for canine cognitive dysfunction, but there are medical aids to help mask the symptoms attributed to the disease as it progresses. Therapies are a major form of symptom masking, such as exercise increase, new toys, and learning new commands have shown increases in memory. Changing the dog's diet is also a helpful tool in improving memory and cell membrane health.[citation needed] Medication is also one of the most effective ways to mask the symptoms of CCD. Anipryl (selegiline) is the only drug that has been approved for use on dogs with canine cognitive dysfunction.[5] Anipryl is a drug that is used to treat humans with Parkinson's disease, and has shown drastic improvement in the quality of life in dogs living with CCD.[6]
## Precautions[edit]
In order for dogs to cope with CCD with as little frustration as possible, it is important to make the transition into the progression of the disease easy and stress free. The environment in which the dog lives is prevalent in the coping process. To keep the environment familiar to the dog, consider eliminating clutter around the house to prevent obstacles for the dog, keep commands short as to avoid confusion, immerse the dog in short, friendly play sessions, and develop a feeding and watering schedule that sticks to a routine. Avoid changing decorations or rearranging furniture in the house, as this will avoid confusion and problems with moving around. When these precautions are taken, the dog will have a higher chance of living longer with as little effects of CCD as possible.[7]
## See also[edit]
* Feline cognitive dysfunction
## References[edit]
1. ^ "Cognitive Dysfunction Syndrome in Dogs". Pets.webmd.com. Retrieved 2014-01-28.
2. ^ a b Andrea Menashe (2013-10-30). "Pet Talk: Canine Cognitive Dysfunction Syndrome much more manageable when caught early". OregonLive.com. Retrieved 2014-01-28.
3. ^ "Dementia (Geriatric) in Dogs". petMD. Retrieved 2014-01-28.
4. ^ "Cognitive Dysfunction Syndrome in Dogs" (PDF). Lap of Love Educational Pet Disease Series. Archived from the original (PDF) on 2013-09-19.
5. ^ "CDSInDogs". CDSInDogs. Retrieved 2014-01-28.
6. ^ Landsberg, Gary (2005). "Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 29 (3): 471–479. doi:10.1016/j.pnpbp.2004.12.012. PMID 15795056.
7. ^ "Senior Dog Care: Older Dogs, Aged Minds: Dealing With Dog Dementia". Drsfostersmith.com. 2013-08-26. Retrieved 2014-01-28.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Canine cognitive dysfunction
|
None
| 7,542 |
wikipedia
|
https://en.wikipedia.org/wiki/Canine_cognitive_dysfunction
| 2021-01-18T18:56:16 |
{"wikidata": ["Q17115842"]}
|
In a highly inbred Arab family with ataxia-telangiectasia of complementation group A (ATA; 208900), Ziv et al. (1992) found 3 individuals who had ataxia, hypotonia, microcephaly, and congenital cataracts with nystagmus. Mental retardation was also observed in 1 of the 3 persons. The one individual appeared to be affected with both ataxia-telangiectasia and the AMC syndrome. Findings of the AMC syndrome resembled the Marinesco-Sjogren syndrome (MSS; 248800); however, microcephaly is not part of MSS, and mental retardation was present in only 1 of the AMC patients. Cataract is not characteristic of any of the known disorders that simulate ataxia-telangiectasia. That the AMC syndrome was an entity separate from AT in the Arab family was indicated by linkage studies.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Eyes \- Congenital cataracts \- Nystagmus NEUROLOGIC Central Nervous System \- Ataxia \- Hypotonia \- Mental retardation ▲ 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
|
ATAXIA-MICROCEPHALY-CATARACT SYNDROME
|
c0796056
| 7,543 |
omim
|
https://www.omim.org/entry/208870
| 2019-09-22T16:30:39 |
{"mesh": ["C563086"], "omim": ["208870"], "synonyms": ["Alternative titles", "AMC SYNDROME"]}
|
A number sign (#) is used with this entry because autosomal recessive spastic paraplegia-44 (SPG44) can be caused by homozygous mutation in the GJC2 gene (608803) on chromosome 1q42.
Clinical Features
Orthmann-Murphy et al. (2009) reported 3 members of a large Italian family with spastic paraplegia. Although mild symptoms were reported in the first or second decades, there was more severe progression with disability in the third decade. Physical examination at age 39, 36, and 53 years, respectively, showed lower limb spasticity, spastic gait, extensor plantar responses, hyperreflexia, and pes cavus. One patient used a walker, and 1 was wheelchair-bound. Other features included dysarthria, loss of finger dexterity, dysmetria, and intention tremor on finger-to-nose and heel-to-knee testing. Nystagmus was not present. One patient had lumbar hyperlordosis, and another had scoliosis. The 39-year-old proband presented with an 8-year history of slowly progressive walking difficulties, leg stiffness, and slurred speech. He reported feelings of clumsiness since his teens but was fit for military service at age 18. His 36-year-old brother had minimal motor difficulties since infancy and mild learning impairment at school. He also reported mild intention tremor during late-childhood and a few tonic-clonic seizures, mainly febrile, between childhood and his early teens. A 53-year-old female cousin had earlier onset in her teens and was wheelchair-bound by age 30. She had mild cognitive impairment. In her forties, she developed urinary incontinence, episodic painful spasms in the lower limbs, and constipation. At the time of the report, she had upper limb involvement, decreased sensation in the limbs, severe dorsal scoliosis, bilateral pes cavus, and ankle contractures. Brain MRI showed a hypomyelinating leukodystrophy and thin corpus callosum in all 3 patients. Central nerve conduction studies (motor evoked potentials, MEP) were prolonged in all patients, but peripheral nerve conduction was normal.
Molecular Genetics
In 3 affected members of an Italian family with SPG44, Orthmann-Murphy et al. (2009) identified a homozygous mutation in the GJC2 gene (I33M; 608803.0008). Heterozygous family members were unaffected. The authors noted that the phenotype was less severe than hypomyelinating leukoencephalopathy-2 (HLD2; 608804), an allelic disorder.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss (in 1 of 3 patients) Eyes \- Slow saccades ABDOMEN Gastrointestinal \- Constipation (in 1 of 3 patients) GENITOURINARY Bladder \- Urinary incontinence (in 1 of 3 patients) SKELETAL Spine \- Scoliosis (in 2 of 3 patients) Feet \- Pes cavus NEUROLOGIC Central Nervous System \- Lower limb spasticity \- Spastic gait \- Upper limb spasticity \- Hyperreflexia \- Extensor plantar responses \- Dysarthria \- Intention tremor \- Dysmetria \- Cerebellar ataxia \- Seizures (in 1 of 3 patients) \- Cognitive impairment, mild (in 2 of 3 patients) \- Hypomyelinating leukoencephalopathy \- Thin corpus callosum Peripheral Nervous System \- Decreased distal sensation (in 1 of 3 patients) MISCELLANEOUS \- Onset of mild symptoms in first or second decade \- Progression in adulthood \- Loss of independent ambulation (in 2 of 3 patients) \- One family has been reported (last curated January 2010) MOLECULAR BASIS \- Caused by mutation in the gap junction protein, gamma-2 gene (GJC2, 608803.0008 ) ▲ 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
|
SPASTIC PARAPLEGIA 44, AUTOSOMAL RECESSIVE
|
c2750784
| 7,544 |
omim
|
https://www.omim.org/entry/613206
| 2019-09-22T15:59:21 |
{"doid": ["0110796"], "mesh": ["C567707"], "omim": ["613206"], "orphanet": ["320401"]}
|
For other uses, see Delusion (disambiguation).
See also: Delusional disorder
Firm and fixed belief in that which is based on inadequate grounding
Delusion
SpecialtyPsychiatry
A delusion is a fixed belief that is not amenable to change in light of conflicting evidence.[1] As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, or some other misleading effects of perception.
Delusions have been found to occur in the context of many pathological states (both general physical and mental) and are of particular diagnostic importance in psychotic disorders including schizophrenia, paraphrenia, manic episodes of bipolar disorder, and psychotic depression.
## Contents
* 1 Types
* 1.1 Themes
* 1.2 Persecutory delusions
* 2 Causes
* 2.1 Specific delusions
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Definition
* 5 Criticism
* 6 Gaslighting
* 7 Treatment
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Types[edit]
Delusions are categorized into four different groups:
* 'Bizarre delusion: Delusions are deemed bizarre if they are clearly implausible and not understandable to same-culture peers and do not derive from ordinary life experiences.[2] An example named by the DSM-5 is a belief that someone replaced all of one's internal organs with someone else's without leaving a scar, depending on the organ in question.
* Non-bizarre delusion: A delusion that, though false, is at least technically possible, e.g., the affected person mistakenly believes that they are under constant police surveillance.
* Mood-congruent delusion: Any delusion with content consistent with either a depressive or manic state, e.g., a depressed person believes that news anchors on television highly disapprove of them, or a person in a manic state might believe they are a powerful deity.
* Mood-neutral delusion: A delusion that does not relate to the sufferer's emotional state; for example, a belief that an extra limb is growing out of the back of one's head is neutral to either depression or mania.[3]
### Themes[edit]
In addition to these categories, delusions often manifest according to a consistent theme. Although delusions can have any theme, certain themes are more common. Some of the more common delusion themes are:
* Delusion of control: False belief that another person, group of people, or external force controls one's general thoughts, feelings, impulses, or behaviors.[3]
* Cotard delusion: False belief that one does not exist or that one has died.[4]
* Delusional jealousy: False belief that a spouse or lover is having an affair, with no proof to back up the claim.[3]
* Delusion of guilt or sin (or delusion of self-accusation): Ungrounded feeling of remorse or guilt of delusional intensity.[3]
* Delusion of mind being read: False belief that other people can know one's thoughts.[3]
* Delusion of thought insertion: Belief that another thinks through the mind of the person.[3]
* Delusion of reference: False belief that insignificant remarks, events, or objects in one's environment have personal meaning or significance. "Usually the meaning assigned to these events is negative, but the 'messages' can also have a grandiose quality."[3]
* Erotomania: False belief that another person is in love with them.[3]
* Religious delusion: Belief that the affected person is a god or chosen to act as a god.[5][6]
* Somatic delusion: Delusion whose content pertains to bodily functioning, bodily sensations or physical appearance. Usually the false belief is that the body is somehow diseased, abnormal or changed.[3] A specific example of this delusion is delusional parasitosis: Delusion in which one feels infested with insects, bacteria, mites, spiders, lice, fleas, worms, or other organisms.
* Delusion of poverty: Person strongly believes they are financially incapacitated. Although this type of delusion is less common now, it was particularly widespread in the days preceding state support.[7]
Grandiose delusions or delusions of grandeur are principally a subtype of delusional disorder but could possibly feature as a symptom of schizophrenia and manic episodes of bipolar disorder.[8] Grandiose delusions are characterized by fantastical beliefs that one is famous, omnipotent or otherwise very powerful. The delusions are generally fantastic, often with a supernatural, science-fictional, or religious bent. In colloquial usage, one who overestimates one's own abilities, talents, stature or situation is sometimes said to have "delusions of grandeur". This is generally due to excessive pride, rather than any actual delusions. Grandiose delusions or delusions of grandeur can also be associated with megalomania.[citation needed][9]
### Persecutory delusions[edit]
Main article: Persecutory delusion
Persecutory delusions are the most common type of delusions and involve the theme of being followed, harassed, cheated, poisoned or drugged, conspired against, spied on, attacked, or otherwise obstructed in the pursuit of goals. Persecutory delusions are a condition in which the affected person wrongly believes that they are being persecuted. Specifically, they have been defined as containing two central elements:[10][page needed] The individual thinks that:
* harm is occurring, or is going to occur
* the persecutors have the intention to cause harm
According to the DSM-IV-TR, persecutory delusions are the most common form of delusions in schizophrenia, where the person believes they are "being tormented, followed, sabotaged, tricked, spied on, or ridiculed".[11] In the DSM-IV-TR, persecutory delusions are the main feature of the persecutory type of delusional disorder. When the focus is to remedy some injustice by legal action, they are sometimes called "querulous paranoia".[12]
## Causes[edit]
See also: Psychosis (causes)
Explaining the causes of delusions continues to be challenging and several theories have been developed.[13] One is the genetic or biological theory, which states that close relatives of people with delusional disorder are at increased risk of delusional traits. Another theory is the dysfunctional cognitive processing, which states that delusions may arise from distorted ways people have of explaining life to themselves. A third theory is called motivated or defensive delusions. This one states that some of those persons who are predisposed might suffer the onset of delusional disorder in those moments when coping with life and maintaining high self-esteem becomes a significant challenge. In this case, the person views others as the cause of their personal difficulties in order to preserve a positive self-view.[14]
This condition is more common among people who have poor hearing or sight. Also, ongoing stressors have been associated with a higher possibility of developing delusions. Examples of such stressors are immigration, low socioeconomic status, and even possibly the accumulation of smaller daily hassles.[15]
### Specific delusions[edit]
The top two factors mainly concerned in the germination of delusions are disorder of brain functioning and background influences of temperament and personality.[16]
Higher levels of dopamine qualify as a symptom of disorders of brain function. That they are needed to sustain certain delusions was examined by a preliminary study on delusional disorder (a psychotic syndrome) instigated to clarify if schizophrenia had a dopamine psychosis.[17] There were positive results - delusions of jealousy and persecution had different levels of dopamine metabolite HVA and homovanillyl alcohol (which may have been genetic). These can be only regarded as tentative results; the study called for future research with a larger population.
It is simplistic to say that a certain measure of dopamine will bring about a specific delusion. Studies show age[18][19] and gender to be influential and it is most likely that HVA levels change during the life course of some syndromes.[20]
On the influence of personality, it has been said: "Jaspers considered there is a subtle change in personality due to the illness itself; and this creates the condition for the development of the delusional atmosphere in which the delusional intuition arises."[21]
Cultural factors have "a decisive influence in shaping delusions".[22] For example, delusions of guilt and punishment are frequent in a Western, Christian country like Austria, but not in Pakistan, where it is more likely persecution.[23] Similarly, in a series of case studies, delusions of guilt and punishment were found in Austrian patients with Parkinson's being treated with l-dopa, a dopamine agonist.[24]
## Pathophysiology[edit]
The two-factor model of delusions posits that dysfunction in both belief formation systems and belief evaluation systems are necessary for delusions. Dysfunction in evaluations systems localized to the right lateral prefrontal cortex, regardless of delusion content, is supported by neuroimaging studies and is congruent with its role in conflict monitoring in healthy persons. Abnormal activation and reduced volume is seen in people with delusions, as well as in disorders associated with delusions such as frontotemporal dementia, psychosis and Lewy body dementia. Furthermore, lesions to this region are associated with "jumping to conclusions", damage to this region is associated with post-stroke delusions, and hypometabolism this region associated with caudate strokes presenting with delusions.[citation needed]
The aberrant salience model suggests that delusions are a result of people assigning excessive importance to irrelevant stimuli. In support of this hypothesis, regions normally associated with the salience network demonstrate reduced grey matter in people with delusions, and the neurotransmitter dopamine, which is widely implicated in salience processing, is also widely implicated in psychotic disorders.[citation needed]
Specific regions have been associated with specific types of delusions. The volume of the hippocampus and parahippocampus is related to paranoid delusions in Alzheimer's disease, and has been reported to be abnormal post mortem in one person with delusions. Capgras delusions have been associated with occipito-temporal damage and may be related to failure to elicit normal emotions or memories in response to faces.[25]
## Diagnosis[edit]
James Tilly Matthews illustrated this picture of a machine called an “air loom”, which he believed was being used to torture him and others for political purposes.
The modern definition and Jaspers' original criteria have been criticised, as counter-examples can be shown for every defining feature.
Studies on psychiatric patients show that delusions vary in intensity and conviction over time, which suggests that certainty and incorrigibility are not necessary components of a delusional belief.[26]
Delusions do not necessarily have to be false or 'incorrect inferences about external reality'.[27] Some religious or spiritual beliefs by their nature may not be falsifiable, and hence cannot be described as false or incorrect, no matter whether the person holding these beliefs was diagnosed as delusional or not.[28] In other situations the delusion may turn out to be true belief.[29] For example, in delusional jealousy, where a person believes that their partner is being unfaithful (and may even follow them into the bathroom believing them to be seeing their lover even during the briefest of partings), it may actually be true that the partner is having sexual relations with another person. In this case, the delusion does not cease to be a delusion because the content later turns out to be verified as true or the partner actually chose to engage in the behavior of which they were being accused.
In other cases, the belief may be mistakenly assumed to be false by a doctor or psychiatrist assessing it, just because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a person's claims leading to some true beliefs to be erroneously classified as delusional.[30] This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time, her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).
Similar factors have led to criticisms of Jaspers' definition of true delusions as being ultimately 'un-understandable'. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information that might make a belief otherwise interpretable. R. D. Laing's hypothesis has been applied to some forms of projective therapy to "fix" a delusional system so that it cannot be altered by the patient. Psychiatric researchers at Yale University, Ohio State University and the Community Mental Health Center of Middle Georgia have used novels and motion picture films as the focus. Texts, plots and cinematography are discussed and the delusions approached tangentially.[31] This use of fiction to decrease the malleability of a delusion was employed in a joint project by science-fiction author Philip Jose Farmer and Yale psychiatrist A. James Giannini. They wrote the novel Red Orc's Rage, which, recursively, deals with delusional adolescents who are treated with a form of projective therapy. In this novel's fictional setting other novels written by Farmer are discussed and the characters are symbolically integrated into the delusions of fictional patients. This particular novel was then applied to real-life clinical settings.[32]
Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. For instance, if a person was holding a true belief then they will of course persist with it. This can cause the disorder to be misdiagnosed by psychiatrists. These factors have led the psychiatrist Anthony David to note that "there is no acceptable (rather than accepted) definition of a delusion."[33] In practice, psychiatrists tend to diagnose a belief as delusional if it is either patently bizarre, causing significant distress, or excessively pre-occupying the patient, especially if the person is subsequently unswayed in belief by counter-evidence or reasonable arguments.
It is important to distinguish true delusions from other symptoms such as anxiety, fear, or paranoia. To diagnose delusions a mental state examination may be used. This test includes appearance, mood, affect, behavior, rate and continuity of speech, evidence of hallucinations or abnormal beliefs, thought content, orientation to time, place and person, attention and concentration, insight and judgment, as well as short-term memory.[34]
Johnson-Laird suggests that delusions may be viewed as the natural consequence of failure to distinguish conceptual relevance. That is, the person takes irrelevant information and puts it in the form of disconnected experiences, then it is taken to be relevant in a manner that suggests false causal connections. Furthermore, the person takes the relevant information, in the form of counterexamples, and ignores it.[35]
### Definition[edit]
Although non-specific concepts of madness have been around for several thousand years, the psychiatrist and philosopher Karl Jaspers was the first to define the three main criteria for a belief to be considered delusional in his 1913 book General Psychopathology.[36] These criteria are:
* certainty (held with absolute conviction)
* incorrigibility (not changeable by compelling counterargument or proof to the contrary)
* impossibility or falsity of content (implausible, bizarre, or patently untrue)[37]
Furthermore, when a false belief involves a value judgment, it is only considered a delusion if it is so extreme that it cannot be, or never can be proven true. For example: a man claiming that he flew into the Sun and flew back home. This would be considered a delusion,[38] unless he were speaking figuratively, or if the belief had a cultural or religious source.
Robert Trivers writes that delusion is a discrepancy in relation to objective reality, but with a firm conviction in reality of delusional ideas, which is manifested in the "affective basis of delusion" Trivers, Robert (2002). Natural Selection and Social Theory: Selected Papers of Robert Trivers. Oxford University Press. ISBN 978-0-19-513062-1.
## Criticism[edit]
Some psychiatrists criticize the practice of defining one and the same belief as normal in one culture and pathological in another culture for cultural essentialism. They argue that since cultural influences are mixed, including not only parents and teachers but also peers, friends, books and the internet, and the same cultural influence can have different effects depending on earlier cultural influences, the assumption that culture can be boiled down to a few traceable, distinguishable and statistically quantifiable factors and that everything that does not fall in those factors must be biological, is not a justified assumption. Other critical psychiatrists argue that just because a person's belief is unshaken by one influence does not prove that it would remain unshaken by another. For example, a person whose beliefs are not changed by verbal correction from a psychiatrist, which is how delusion is usually diagnosed, may still change his or her mind when observing empirical evidence, only that psychiatry rarely if ever present patients with such situations.[39][40]
## Gaslighting[edit]
Sometimes a correct belief may be mistaken for a delusion, such as when the belief in question is not demonstrably false but is nevertheless considered beyond the realm of possibility. A specific variant of this is when a person is fed lies in an attempt to convince them that they are delusional, a process called gaslighting, after the 1938 play Gaslight, the plot of which centered around the process. Sometimes, gaslighting can be unintentional, for example if a person, or a group of people aim to lie or cover up an issue, it can lead to the victim being gaslighted as well.[41]
## Treatment[edit]
Psychotherapies that may be helpful in delusional disorder include individual psychotherapy, cognitive-behavioral therapy (CBT), and family therapy.
## See also[edit]
* Philosophy portal
* Psychology portal
* Psychiatry portal
* Bizarre object
* Capgras delusion
* Clinical lycanthropy
* Delirium
* Delusional misidentification syndrome
* Folie à deux
* Intrusive thoughts
* Paris syndrome
* Jerusalem syndrome
* Mass hysteria
* Monothematic delusion
* Paranoia
* Pathological jealousy
* Psychosis
* Reduplicative paramnesia
* Prelest
## References[edit]
1. ^ Bortolotti, Lisa (7 June 2013). "Delusions in the DSM 5". Imperfect Cognitions.
2. ^ Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association. 2013.
3. ^ a b c d e f g h i "Delusions". Encyclopedia of Mental Disorders. Advameg.com. Retrieved 22 April 2018.
4. ^ Berrios G.E.; Luque R. (1995). "Cotard Syndrome: clinical analysis of 100 cases". Acta Psychiatrica Scandinavica. 91 (3): 185–188. doi:10.1111/j.1600-0447.1995.tb09764.x. PMID 7625193. S2CID 8764432.
5. ^ "Religious delusions are common symptoms of schizophrenia". Retrieved 17 April 2011.
6. ^ M, Raja. "Religious delusion" (PDF). Archived from the original (PDF) on 22 March 2012. Retrieved 17 April 2011.
7. ^ Barker, P. 1997. Assessment in Psychiatric and Mental Health Nursing in Search of the Whole Person. UK: Nelson Thornes Ltd. P241.
8. ^ Diagnostic and Statistical Manual of Mental Disorders Fourth edition Text Revision (DSM-IV-TR) American Psychiatric Association (2000)
9. ^ Kunert, Hanns Jürgen; Norra, Christine; Hoff, Paul (March 2007). "Theories of Delusional Disorders: An Update and Review". Psychopathology. 40 (3): 191–202. doi:10.1159/000100367. PMID 17337940.
10. ^ Freeman, D. & Garety, P.A. (2004) Paranoia: The Psychology of Persecutory Delusions. Hove: PsychoIogy Press. ISBN 1-84169-522-X
11. ^ Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association. 2000. p. 299. ISBN 0-89042-025-4.
12. ^ Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association. 2000. p. 325. ISBN 0-89042-025-4.
13. ^ Kiran C, Chaudhury S (2009). "Understanding delusions". Industrial Psychiatry Journal. 18 (1): 3–18. doi:10.4103/0972-6748.57851. PMC 3016695. PMID 21234155.
14. ^ "Delusional Disorder". Retrieved 6 August 2010.
15. ^ Kingston C., Schuurmans-Stekhoven J. (2016). "Life hassles and delusional ideation: Scoping the potential role of cognitive and affective mediators". Psychology and Psychotherapy: Theory, Research and Practice. 89 (4): 445–463. doi:10.1111/papt.12089. PMID 26846698.
16. ^ Sims, Andrew (2002). Symptoms in the mind: an introduction to descriptive psychopathology. Philadelphia: W. B. Saunders. p. 127. ISBN 0-7020-2627-1.
17. ^ Morimoto K, Miyatake R, Nakamura M, Watanabe T, Hirao T, Suwaki H (June 2002). "Delusional disorder: molecular genetic evidence for dopamine psychosis". Neuropsychopharmacology. 26 (6): 794–801. doi:10.1016/S0893-133X(01)00421-3. PMID 12007750.
18. ^ Mazure CM, Bowers MB (1 February 1998). "Pretreatment plasma HVA predicts neuroleptic response in manic psychosis". Journal of Affective Disorders. 48 (1): 83–6. doi:10.1016/S0165-0327(97)00159-6. PMID 9495606.
19. ^ Yamada N, Nakajima S, Noguchi T (February 1998). "Age at onset of delusional disorder is dependent on the delusional theme". Acta Psychiatrica Scandinavica. 97 (2): 122–4. doi:10.1111/j.1600-0447.1998.tb09973.x. PMID 9517905. S2CID 39266698.
20. ^ Tamplin A, Goodyer IM, Herbert J (1 February 1998). "Family functioning and parent general health in families of adolescents with major depressive disorder". Journal of Affective Disorders. 48 (1): 1–13. doi:10.1016/S0165-0327(97)00105-5. PMID 9495597.
21. ^ Sims, Andrew (2002). Symptoms in the mind: an introduction to descriptive psychopathology. Philadelphia: W. B. Saunders. p. 128. ISBN 0-7020-2627-1.
22. ^ Draguns JG, Tanaka-Matsumi J (July 2003). "Assessment of psychopathology across and within cultures: issues and findings". Behav Res Ther. 41 (7): 755–76. doi:10.1016/S0005-7967(02)00190-0. PMID 12781244.
23. ^ Stompe T, Friedman A, Ortwein G, et al. (1999). "Comparison of delusions among schizophrenics in Austria and in Pakistan". Psychopathology. 32 (5): 225–34. doi:10.1159/000029094. PMID 10494061. S2CID 25376490.
24. ^ Birkmayer W, Danielczyk W, Neumayer E, Riederer P (1972). "The balance of biogenic amines as condition for normal behaviour". J. Neural Transm. 33 (2): 163–78. doi:10.1007/BF01260902. PMID 4643007. S2CID 28152591.
25. ^ Naasan, George. "The Anatomy of Delusions". In Lehner, T; Miller, B; State, M (eds.). Genomics, Circuits, and Pathways in Clinical Neuropsychiatry. Elsevier Science. pp. 366–369.
26. ^ Myin-Germeys I, Nicolson NA, Delespaul PA (April 2001). "The context of delusional experiences in the daily life of patients with schizophrenia". Psychol Med. 31 (3): 489–98. doi:10.1017/s0033291701003646. PMID 11305857.
27. ^ Spitzer M (1990). "On defining delusions". Compr Psychiatry. 31 (5): 377–97. doi:10.1016/0010-440X(90)90023-L. PMID 2225797.
28. ^ Young, A.W. (2000). "Wondrous strange: The neuropsychology of abnormal beliefs". In Coltheart M.; Davis M. (eds.). Pathologies of belief. Oxford: Blackwell. pp. 47–74. ISBN 0-631-22136-0.
29. ^ Jones E (1999). "The phenomenology of abnormal belief". Philosophy, Psychiatry and Psychology. 6: 1–16.
30. ^ Maher B.A. (1988). "Anomalous experience and delusional thinking: The logic of explanations". In Oltmanns T.; Maher B. (eds.). Delusional Beliefs. New York: Wiley Interscience. ISBN 0-471-83635-4.
31. ^ Giannini AJ (2001). "Use of fiction in therapy". Psychiatric Times. 18 (7): 56.
32. ^ AJ Giannini. Afterword. (in) PJ Farmer. Red Orc's Rage.NY, Tor Books, 1991, pp.279-282.
33. ^ David AS (1999). "On the impossibility of defining delusions". Philosophy, Psychiatry and Psychology. 6 (1): 17–20.
34. ^ "Diagnostic Test List for Delusions". Retrieved 6 August 2010.
35. ^ "A New Definition of Delusional Ideation in Terms of Model Restriction". Retrieved 6 August 2010.[permanent dead link]
36. ^ Jaspers, Karl (1913). Allgemeine Psychopathologie. Ein Leitfaden für Studierende, Ärzte und Psychologen. Berlin: J. Springer.
37. ^ Jaspers 1997, p. 106
38. ^ "Terms in the Field of Psychiatry and Neurology". Archived from the original on 19 August 2010. Retrieved 6 August 2010.
39. ^ D. Double 2006 "Critical Psychiatry: The Limits of Madness"
40. ^ Gavin Davidson, Jim Campbell, Ciarán Shannon 2015 "Models of Mental Health"
41. ^ The Sociopath Next Door by Martha Stout (2006) Harmony. ISBN 0767915828.
Cited text
* Jaspers, Karl (1997). General Psychopathology. 1. Baltimore: Johns Hopkins University Press. ISBN 0-8018-5775-9.
## Further reading[edit]
* Arnold, K.; Vakhrusheva, J. (2015). "Resist the negation reflex: Minimizing reactance in psychotherapy of delusions" (PDF). Psychosis. 8 (2): 166–175. doi:10.1080/17522439.2015.1095229. S2CID 146386637.
* Bell V, Halligan PW, Ellis H (2003). "Beliefs about delusions" (PDF). The Psychologist. 16 (8): 418–423. Archived from the original (PDF) on 28 July 2011.
* Blackwood, Nigel J.; Howard, Robert J.; Bentall, Richard P.; Murray, Robin M. (April 2001). "Cognitive Neuropsychiatric Models of Persecutory Delusions". American Journal of Psychiatry. 158 (4): 527–539. doi:10.1176/appi.ajp.158.4.527. PMID 11282685.
* Coltheart M.; Davies M., eds. (2000). Pathologies of belief. Oxford: Blackwell. ISBN 0-631-22136-0.
* Persaud, R. (2003). From the Edge of the Couch: Bizarre Psychiatric Cases and What They Teach Us About Ourselves. Bantam. ISBN 0-553-81346-3.
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*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Delusion
|
c0011253
| 7,545 |
wikipedia
|
https://en.wikipedia.org/wiki/Delusion
| 2021-01-18T18:49:44 |
{"mesh": ["D003702"], "umls": ["C0011253"], "wikidata": ["Q189643"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of congenital diaphragmatic hernia (CDH), see DIH1 (142340).
Cytogenetics
Shimokawa et al. (2005) reported a 37-week-old infant with left diaphragmatic hernia who had a 46,XY,del(8)(p23.1p23.1) karyotype. Surgical repair was unsuccessful, and postmortem examination showed hypoplasia of the left lung and atrial septal defect. Microsatellite analysis showed that the deletion was of paternal origin, and his parents did not carry 8p23.1 polymorphic inversion. Shimokawa et al. (2005) stated that this was the fourth report of CDH associated with 8p23.1 deletion (see Pecile et al., 1990; Faivre et al., 1998; Borys and Taxy, 2004). The form of CDH associated with 8p23.1 deletion has been designated here as DIH2.
By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving 15q26.2, and 1 male infant had a deletion in band 8p23.1.
Muscle \- Agenesis of the diaphragm Inheritance \- Autosomal recessive vs. multifactorial ▲ 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
|
DIAPHRAGMATIC HERNIA 2
|
c0235833
| 7,546 |
omim
|
https://www.omim.org/entry/222400
| 2019-09-22T16:28:43 |
{"doid": ["3827"], "mesh": ["D065630"], "omim": ["222400"], "orphanet": ["2140"]}
|
A number sign (#) is used with this entry because transient bullous dermolysis of the newborn (TBDN) is caused by heterozygous or compound heterozygous mutation in the COL7A1 gene (120120) on chromosome 7p21.
Autosomal dominant and autosomal recessive epidermolysis bullosa dystrophica (131750, 226600) are allelic disorders.
Description
Transient bullous dermolysis of the newborn is a rare form of dystrophic epidermolysis bullosa (DEB) that presents with neonatal skin blistering but usually improves markedly during early life and even remits completely. Skin biopsies reveal abnormal intraepidermal accumulation of type VII collagen, which results in poorly constructed anchoring fibrils and a sublamina densa plane of blister formation (summary by Fassihi et al., 2005).
Clinical Features
Hashimoto et al. (1985) first described this disorder in an African American male delivered by cesarean section who developed large bullae on his extremities and in other friction areas soon after birth. The bullae healed rapidly, leaving hypopigmentation, but no scars or milia. Occasional new lesions continued to appear for 4 months but not after. Reexamination 12 months later showed a normal healthy infant with only residual hypopigmentation in some of the previously involved areas. Histologic and electron microscopic examinations revealed a subepidermal bulla that was ultrastructurally a subbasal lamina separation associated with collagenolysis and damage to the anchoring fibrils. There was no significant family history.
Hashimoto et al. (1989) reported 2 additional cases of transient bullous dermolysis of the newborn. One was a white boy who had normal skin at birth, but developed multiple blisters soon after. The oral mucous membranes were not affected. All lesions healed within 4 months without scars but with many milia. No blisters or milia were apparent at age 17 months. The second patient was a Japanese girl who showed extensive denudation of her hands at birth. Generalized blisters and involvement of the oral mucous membrane developed. Blistering stopped within 1.25 months, and all lesions healed without scars. The blisters were subepidermal in both cases. Electron microscopy revealed collagenolysis, diminution or loss of anchoring fibrils, and stellate inclusions in dilated rough endoplasmic reticulum in the keratinocytes of the lower epidermis.
Fine et al. (1990) also described cases. The usual finding is blistering during the first months of life but none after age 1 year. Immunohistochemical studies showed granular basilar keratinocyte perinuclear intracytoplasmic deposits of COL7A1, rather than exclusively linear basement membrane deposits. Fine et al. (1990) proposed a defect in the intracytoplasmic packaging or in the transport of type VII collagen within basilar keratinocytes.
Fine et al. (1991, 1993) performed longitudinal studies of 9 patients from 4 families with transient bullous dermolysis of the newborn. Clinical features included the development of generalized blisters and skin erosions at birth followed by milia formation. Nail dystrophy was also apparent, but nails tended to regrow normally. In 3 families, blister formation disappeared by age 6 months; in the fourth family, blister activity became minimal within the first 2 years of life although some lesions continued to occur into the thirties. During the blistering period, type VII collagen was retained within basilar keratinocytes rather than incorporated into the dermal-epidermal junction. However, following complete cessation of or marked reduction in the extent of blister formation, type VII collagen was expressed in normal intensity in linear distribution along the dermal-epidermal junction, identical to that observed in normal human skin. Fine et al. (1991, 1993) concluded that the temporary presence of mechanical fragility and blister formation reflected a delay in transport and integration of type VII collagen from basilar keratinocytes into skin basement membrane.
McCollough et al. (1991) reported an infant with this disorder. She was born with blisters on the hands, feet, trunk, face, and oral mucosa which healed without scarring. By age 6 months the patient had developed only an occasional blister. The mother stated that during the first 6 months of life she also had had blisters, which spontaneously resolved at 6 months of age. Intraepidermal type VII collagen was demonstrated immunohistologically.
Fassihi et al. (2005) reported autosomal dominant TBDN in a proband, his father, and his paternal grandfather. The authors performed a skin biopsy analysis in the affected individuals, which showed persistence of some intraepidermal type VIII collagen, suggesting that despite the clinical resolution, some abnormalities of type VII collagen processing and secretion may persist.
Molecular Genetics
In affected members of a family with autosomal dominant transient bullous dermolysis of the newborn reported by Fine et al. (1993), Christiano et al. (1997) identified a heterozygous mutation in the COL7A1 gene (120120.0039).
In a patient with TBDN, Hammami-Hauasli et al. (1998) identified compound heterozygosity for 2 mutations in the COL7A1 gene (G2251E, 120120.0014; G1519D, 120120.0015). Heterozygous carriers of the G2251E allele had normal skin but isolated toenail dystrophy (607523).
In affected males in 3 generations of a family segregating TBDN, Fassihi et al. (2005) identified a heterozygous mutation in the COL7A1 gene (120120.0044).
INHERITANCE \- Autosomal dominant \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Epidermolysis bullosa, dystrophic \- Skin fragility \- Blisters \- Milia \- Mild atrophic scarring Electron Microscopy \- Sublamina densa level of tissue separation beneath basal membrane \- Decreased number of anchoring fibrils at dermal-epidermal junction \- Hypotrophic anchoring fibrils \- Retention of COL7A1 within endoplasmic reticulum in epidermal keratinocytes \- Decreased staining for collagen VII at the dermal-epidermal junction \- Anchoring fibrils revert to normal with clinical resolution of the disease Nails \- Nail dystrophy MISCELLANEOUS \- Onset at birth \- Skin lesions resolve between 6 months and 2 years of age \- Some patients have milder persistent blistering MOLECULAR BASIS \- Caused by mutation in the collagen type VII, alpha-1 gene (COL7A1, 120120.0014 ). ▲ 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
|
TRANSIENT BULLOUS DERMOLYSIS OF THE NEWBORN
|
c1851573
| 7,547 |
omim
|
https://www.omim.org/entry/131705
| 2019-09-22T16:41:33 |
{"doid": ["0111345"], "mesh": ["C536979"], "omim": ["131705"], "orphanet": ["79411"], "synonyms": ["Alternative titles", "EPIDERMOLYSIS BULLOSA DYSTROPHICA, NEONATAL FORM", "DYSTROPHIC EPIDERMOLYSIS BULLOSA, NEONATAL"], "genereviews": ["NBK1304"]}
|
Idiopathic chronic eosinophilic pneumonia (ICEP) is a very rare, severe, interstitial lung disease of insidious onset with subacute or chronic non-specific respiratory manifestations (dyspnea, cough, wheezing) often associated with systemic manifestations (fatigue, malaise, weight loss).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Idiopathic chronic eosinophilic pneumonia
|
c0008680
| 7,548 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2902
| 2021-01-23T18:20:26 |
{"umls": ["C0008680", "C2930941"], "icd-10": ["J82"], "synonyms": ["Chronic eosinophilic pneumonia"]}
|
A rare, pure or complex subtype of hereditary spastic paraplegia, with highly variable phenotype, typically characterized by childhood-onset of minimally progressive, bilateral, mainly symmetric lower limb spasticity and weakness, associated with pes cavus, diminished vibration sense, sphincter disturbances and/or urinary bladder hyperactivity. Additional associated manifestations may include scoliosis, mild intellectual disability, optic atrophy, axonal motor neuropathy and/or distal amyotrophy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal dominant spastic paraplegia type 3
|
c2931355
| 7,549 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100984
| 2021-01-23T17:03:27 |
{"gard": ["5041"], "mesh": ["C536864"], "omim": ["182600"], "umls": ["C2931355"], "icd-10": ["G11.4"], "synonyms": ["Strümpell disease"]}
|
Infectious disease caused by poliovirus
"Poliomyelitis" redirects here. For the virus, see Poliovirus. For other uses, see Polio (disambiguation).
Polio
Other namesPoliomyelitis, infantile paralysis
A man with a smaller right leg due to poliomyelitis
Pronunciation
* /ˌpoʊlioʊˌmaɪəˈlaɪtɪs/
SpecialtyNeurology, Infectious disease
SymptomsMuscle weakness resulting in an inability to move[1]
ComplicationsPost-polio syndrome[2]
Usual onsetFew hours to days[1][3]
CausesPoliovirus spread by fecal-oral route[1]
Diagnostic methodFinding the virus in the feces or antibodies in the blood[1]
PreventionPolio vaccine[3]
TreatmentSupportive care[3]
Frequency136 people (2018)[4]
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus.[1] In about 0.5 percent of cases, it moves from the gut to affect the central nervous system and there is muscle weakness resulting in a flaccid paralysis.[1] This can occur over a few hours to a few days.[1][3] The weakness most often involves the legs, but may less commonly involve the muscles of the head, neck and diaphragm.[1] Many people fully recover.[1] In those with muscle weakness, about 2 to 5 percent of children and 15 to 30 percent of adults die.[1] For all those infected, in up to 70 percent of infections there are no symptoms.[1] Another 25 percent of people have minor symptoms such as fever and a sore throat, and up to 5 percent have headache, neck stiffness and pains in the arms and legs.[1][3] These people are usually back to normal within one or two weeks.[1] Years after recovery, post-polio syndrome may occur, with a slow development of muscle weakness similar to that which the person had during the initial infection.[2]
Poliovirus is usually spread from person to person through infected fecal matter entering the mouth.[1] It may also be spread by food or water containing human feces and less commonly from infected saliva.[1][3] Those who are infected may spread the disease for up to six weeks even if no symptoms are present.[1] The disease may be diagnosed by finding the virus in the feces or detecting antibodies against it in the blood.[1] The disease occurs naturally only in humans.[1]
The disease is preventable with the polio vaccine; however, multiple doses are required for it to be effective.[3] The US Centers for Disease Control and Prevention recommends polio vaccination boosters for travelers and those who live in countries where the disease is endemic.[5] Once infected there is no specific treatment.[3] In 2018, there were 33 cases of wild polio and 104 cases of vaccine-derived polio.[4] This is down from 350,000 wild cases in 1988.[3] In 2018, the wild disease was spread between people only in Afghanistan and Pakistan.[4] In 2019 there were 175 cases of wild polio and 364 cases of vaccine-derived polio.[6]
Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art.[1] The disease was first recognized as a distinct condition by the English physician Michael Underwood in 1789[1] and the virus that causes it was first identified in 1909 by the Austrian immunologist Karl Landsteiner.[7] Major outbreaks started to occur in the late 19th century in Europe and the United States.[1] In the 20th century it became one of the most worrying childhood diseases in these areas.[8] The first polio vaccine was developed in the 1950s by Jonas Salk.[9] Soon after, Albert Sabin developed an oral vaccine, which has become the world standard.[10]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Transmission
* 3 Pathophysiology
* 3.1 Paralytic polio
* 3.1.1 Spinal polio
* 3.1.2 Bulbar polio
* 3.1.3 Bulbospinal polio
* 4 Diagnosis
* 5 Prevention
* 5.1 Passive immunization
* 5.2 Vaccine
* 6 Treatment
* 7 Prognosis
* 7.1 Recovery
* 7.2 Complications
* 7.3 Post-polio syndrome
* 8 Epidemiology
* 8.1 Afghanistan and Pakistan
* 8.2 Americas
* 8.3 Western Pacific
* 8.4 Europe
* 8.5 Southeast Asia
* 8.6 Middle East
* 8.7 Africa
* 9 History
* 9.1 Etymology
* 10 Research
* 11 References
* 12 Further reading
* 13 External links
## Signs and symptoms
Outcomes of poliovirus infection Outcome Proportion of cases[1]
No symptoms 72%
Minor illness 24%
Nonparalytic aseptic
meningitis 1–5%
Paralytic poliomyelitis 0.1–0.5%
— Spinal polio 79% of paralytic cases
— Bulbospinal polio 19% of paralytic cases
— Bulbar polio 2% of paralytic cases
The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of poliovirus. Two basic patterns of polio infection are described: a minor illness which does not involve the central nervous system (CNS), sometimes called abortive poliomyelitis, and a major illness involving the CNS, which may be paralytic or nonparalytic.[11] In most people with a normal immune system, a poliovirus infection is asymptomatic. Rarely, the infection produces minor symptoms; these may include upper respiratory tract infection (sore throat and fever), gastrointestinal disturbances (nausea, vomiting, abdominal pain, constipation or, rarely, diarrhea), and influenza-like illness.[1]
The virus enters the central nervous system in about 1 percent of infections. Most patients with CNS involvement develop nonparalytic aseptic meningitis, with symptoms of headache, neck, back, abdominal and extremity pain, fever, vomiting, lethargy, and irritability.[12][13] About one to five in 1000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly controlled, and, finally, completely paralyzed; this condition is known as acute flaccid paralysis.[14] Depending on the site of paralysis, paralytic poliomyelitis is classified as spinal, bulbar, or bulbospinal. Encephalitis, an infection of the brain tissue itself, can occur in rare cases, and is usually restricted to infants. It is characterized by confusion, changes in mental status, headaches, fever, and, less commonly, seizures and spastic paralysis.[15]
## Cause
Main article: Poliovirus
A TEM micrograph of poliovirus
Poliomyelitis is caused by infection with a member of the genus Enterovirus known as poliovirus (PV). This group of RNA viruses colonize the gastrointestinal tract[16] – specifically the oropharynx and the intestine. The incubation time (to the first signs and symptoms) ranges from three to 35 days, with a more common span of six to 20 days.[1] PV infects and causes disease in humans alone.[17] Its structure is very simple, composed of a single (+) sense RNA genome enclosed in a protein shell called a capsid.[17] In addition to protecting the virus' genetic material, the capsid proteins enable poliovirus to infect certain types of cells. Three serotypes of poliovirus have been identified – poliovirus type 1 (PV1), type 2 (PV2), and type 3 (PV3) – each with a slightly different capsid protein.[18] All three are extremely virulent and produce the same disease symptoms.[17] PV1 is the most commonly encountered form, and the one most closely associated with paralysis.[19]
Individuals who are exposed to the virus, either through infection or by immunization with polio vaccine, develop immunity. In immune individuals, IgA antibodies against poliovirus are present in the tonsils and gastrointestinal tract, and are able to block virus replication; IgG and IgM antibodies against PV can prevent the spread of the virus to motor neurons of the central nervous system.[20] Infection or vaccination with one serotype of poliovirus does not provide immunity against the other serotypes, and full immunity requires exposure to each serotype.[20]
A rare condition with a similar presentation, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses.[21]
### Transmission
Poliomyelitis is highly contagious via the fecal-oral (intestinal source) and the oral-oral (oropharyngeal source) routes.[20] In endemic areas, wild polioviruses can infect virtually the entire human population.[22] It is seasonal in temperate climates, with peak transmission occurring in summer and autumn.[20] These seasonal differences are far less pronounced in tropical areas.[22] The time between first exposure and first symptoms, known as the incubation period, is usually 6 to 20 days, with a maximum range of 3 to 35 days.[23] Virus particles are excreted in the feces for several weeks following initial infection.[23] The disease is transmitted primarily via the fecal-oral route, by ingesting contaminated food or water. It is occasionally transmitted via the oral-oral route,[19] a mode especially visible in areas with good sanitation and hygiene.[20] Polio is most infectious between 7 and 10 days before and after the appearance of symptoms, but transmission is possible as long as the virus remains in the saliva or feces.[19]
Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency,[24] malnutrition,[25] physical activity immediately following the onset of paralysis,[26] skeletal muscle injury due to injection of vaccines or therapeutic agents,[27] and pregnancy.[28] Although the virus can cross the maternal-fetal barrier during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination.[29] Maternal antibodies also cross the placenta, providing passive immunity that protects the infant from polio infection during the first few months of life.[30]
## Pathophysiology
A blockage of the lumbar anterior spinal cord artery due to polio (PV3)
Poliovirus enters the body through the mouth, infecting the first cells with which it comes in contact – the pharynx and intestinal mucosa. It gains entry by binding to an immunoglobulin-like receptor, known as the poliovirus receptor or CD155, on the cell membrane.[31] The virus then hijacks the host cell's own machinery, and begins to replicate. Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymphoid tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph nodes, where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream.[32]
Known as viremia, the presence of a virus in the bloodstream enables it to be widely distributed throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long periods of time, sometimes as long as 17 weeks.[33] In a small percentage of cases, it can spread and replicate in other sites, such as brown fat, the reticuloendothelial tissues, and muscle.[34] This sustained replication causes a major viremia, and leads to the development of minor influenza-like symptoms. Rarely, this may progress and the virus may invade the central nervous system, provoking a local inflammatory response. In most cases, this causes a self-limiting inflammation of the meninges, the layers of tissue surrounding the brain, which is known as nonparalytic aseptic meningitis.[12] Penetration of the CNS provides no known benefit to the virus, and is quite possibly an incidental deviation of a normal gastrointestinal infection.[35] The mechanisms by which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a chance event – largely independent of the age, gender, or socioeconomic position of the individual.[35]
### Paralytic polio
Denervation of skeletal muscle tissue secondary to poliovirus infection can lead to paralysis.
In around 1 percent of infections, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within the spinal cord, brain stem, or motor cortex. This leads to the development of paralytic poliomyelitis, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS affected.
The destruction of neuronal cells produces lesions within the spinal ganglia; these may also occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar nuclei.[35] Inflammation associated with nerve cell destruction often alters the color and appearance of the gray matter in the spinal column, causing it to appear reddish and swollen.[12] Other destructive changes associated with paralytic disease occur in the forebrain region, specifically the hypothalamus and thalamus.[35] The molecular mechanisms by which poliovirus causes paralytic disease are poorly understood.
Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability, constipation, or difficulty urinating. Paralysis generally develops one to ten days after early symptoms begin, progresses for two to three days, and is usually complete by the time the fever breaks.[36]
The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases.[37] In children under five years of age, paralysis of one leg is most common; in adults, extensive paralysis of the chest and abdomen also affecting all four limbs – quadriplegia – is more likely.[38] Paralysis rates also vary depending on the serotype of the infecting poliovirus; the highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one in 2,000) are associated with type 2.[39]
#### Spinal polio
The location of motor neurons in the anterior horn cells of the spinal column
Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the motor neurons of the anterior horn cells, or the ventral (front) grey matter section in the spinal column, which are responsible for movement of the muscles, including those of the trunk, limbs, and the intercostal muscles.[14] Virus invasion causes inflammation of the nerve cells, leading to damage or destruction of motor neuron ganglia. When spinal neurons die, Wallerian degeneration takes place, leading to weakness of those muscles formerly innervated by the now-dead neurons.[40] With the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles atrophy, becoming weak, floppy and poorly controlled, and finally completely paralyzed.[14] Maximum paralysis progresses rapidly (two to four days), and usually involves fever and muscle pain. Deep tendon reflexes are also affected, and are typically absent or diminished; sensation (the ability to feel) in the paralyzed limbs, however, is not affected.[41]
The extent of spinal paralysis depends on the region of the cord affected, which may be cervical, thoracic, or lumbar.[42] The virus may affect muscles on both sides of the body, but more often the paralysis is asymmetrical.[32] Any limb or combination of limbs may be affected – one leg, one arm, or both legs and both arms. Paralysis is often more severe proximally (where the limb joins the body) than distally (the fingertips and toes).[32]
#### Bulbar polio
The location and anatomy of the bulbar region (in orange)
Making up about two percent of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the bulbar region of the brain stem.[1] The bulbar region is a white matter pathway that connects the cerebral cortex to the brain stem. The destruction of these nerves weakens the muscles supplied by the cranial nerves, producing symptoms of encephalitis, and causes difficulty breathing, speaking and swallowing.[13] Critical nerves affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart, intestines, and lungs), and the accessory nerve (which controls upper neck movement). Due to the effect on swallowing, secretions of mucus may build up in the airway, causing suffocation.[36] Other signs and symptoms include facial weakness (caused by destruction of the trigeminal nerve and facial nerve, which innervate the cheeks, tear ducts, gums, and muscles of the face, among other structures), double vision, difficulty in chewing, and abnormal respiratory rate, depth, and rhythm (which may lead to respiratory arrest). Pulmonary edema and shock are also possible and may be fatal.[42]
#### Bulbospinal polio
Approximately 19 percent of all paralytic polio cases have both bulbar and spinal symptoms; this subtype is called respiratory or bulbospinal polio.[1] Here, the virus affects the upper part of the cervical spinal cord (cervical vertebrae C3 through C5), and paralysis of the diaphragm occurs. The critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate the lungs) and those that drive the muscles needed for swallowing. By destroying these nerves, this form of polio affects breathing, making it difficult or impossible for the patient to breathe without the support of a ventilator. It can lead to paralysis of the arms and legs and may also affect swallowing and heart functions.[43]
## Diagnosis
Paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected limbs that cannot be attributed to another apparent cause, and without sensory or cognitive loss.[44]
A laboratory diagnosis is usually made based on recovery of poliovirus from a stool sample or a swab of the pharynx. Antibodies to poliovirus can be diagnostic, and are generally detected in the blood of infected patients early in the course of infection.[1] Analysis of the patient's cerebrospinal fluid (CSF), which is collected by a lumbar puncture ("spinal tap"), reveals an increased number of white blood cells (primarily lymphocytes) and a mildly elevated protein level. Detection of virus in the CSF is diagnostic of paralytic polio, but rarely occurs.[1]
If poliovirus is isolated from a patient experiencing acute flaccid paralysis, it is further tested through oligonucleotide mapping (genetic fingerprinting), or more recently by PCR amplification, to determine whether it is "wild type" (that is, the virus encountered in nature) or "vaccine type" (derived from a strain of poliovirus used to produce polio vaccine).[45] It is important to determine the source of the virus because for each reported case of paralytic polio caused by wild poliovirus, an estimated 200 to 3,000 other contagious asymptomatic carriers exist.[46]
## Prevention
### Passive immunization
In 1950, William Hammon at the University of Pittsburgh purified the gamma globulin component of the blood plasma of polio survivors.[47] Hammon proposed the gamma globulin, which contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and reduce the severity of disease in other patients who had contracted polio. The results of a large clinical trial were promising; the gamma globulin was shown to be about 80 percent effective in preventing the development of paralytic poliomyelitis.[48] It was also shown to reduce the severity of the disease in patients who developed polio.[47] Due to the limited supply of blood plasma gamma globulin was later deemed impractical for widespread use and the medical community focused on the development of a polio vaccine.[49]
### Vaccine
Main article: Polio vaccine
A child receiving an oral polio vaccine
Two types of vaccine are used throughout the world to combat polio. Both types induce immunity to polio, efficiently blocking person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community (so-called herd immunity).[50]
The first candidate polio vaccine, based on one serotype of a live but attenuated (weakened) virus, was developed by the virologist Hilary Koprowski. Koprowski's prototype vaccine was given to an eight-year-old boy on 27 February 1950.[51] Koprowski continued to work on the vaccine throughout the 1950s, leading to large-scale trials in the then Belgian Congo and the vaccination of seven million children in Poland against serotypes PV1 and PV3 between 1958 and 1960.[52]
The second inactivated polio virus vaccine was developed in 1952 by Jonas Salk at the University of Pittsburgh, and announced to the world on 12 April 1955.[53][54] The Salk vaccine, or inactivated poliovirus vaccine, is based on poliovirus grown in a type of monkey kidney tissue culture (vero cell line), which is chemically inactivated with formalin.[20] After two doses of inactivated poliovirus vaccine (given by injection), 90 percent or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99 percent are immune to poliovirus following three doses.[1]
Subsequently, Albert Sabin developed another live, oral polio vaccine. It was produced by the repeated passage of the virus through nonhuman cells at subphysiological temperatures.[55] The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine strain is unable to replicate efficiently within nervous system tissue.[56] A single dose of Sabin's oral polio vaccine produces immunity to all three poliovirus serotypes in about 50 percent of recipients. Three doses of live-attenuated oral vaccine produce protective antibody to all three poliovirus types in more than 95 percent of recipients.[1] Human trials of Sabin's vaccine began in 1957,[57] and in 1958 it was selected, in competition with the live vaccines of Koprowski and other researchers, by the US National Institutes of Health.[52] Licensed in 1962,[57] it rapidly became the only polio vaccine used worldwide.[52]
Wild polio vs cVDVP cases (2000–2019)
Because the oral polio vaccine is inexpensive, easy to administer, and produces excellent immunity in the intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been the vaccine of choice for controlling poliomyelitis in many countries.[58] On very rare occasions (about one case per 750,000 vaccine recipients), the attenuated virus in the oral polio vaccine reverts into a form that can paralyze.[23] In 2017, cases caused by vaccine-derived poliovirus (cVDPV) outnumbered wild poliovirus cases for the first time, due to wild polio cases hitting record lows and relaxed vaccination levels.[59] Most industrialized countries have switched to inactivated polio vaccine, which cannot revert, either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine.[60]
## Treatment
There is no cure for polio. The focus of modern treatment has been on providing relief of symptoms, speeding recovery and preventing complications. Supportive measures include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate exercise and a nutritious diet.[61] Treatment of polio often requires long-term rehabilitation, including occupational therapy, physical therapy, braces, corrective shoes and, in some cases, orthopedic surgery.[42]
Portable ventilators may be required to support breathing. Historically, a noninvasive, negative-pressure ventilator, more commonly called an iron lung, was used to artificially maintain respiration during an acute polio infection until a person could breathe independently (generally about one to two weeks). Today, many polio survivors with permanent respiratory paralysis use modern jacket-type negative-pressure ventilators worn over the chest and abdomen.[62]
Other historical treatments for polio include hydrotherapy, electrotherapy, massage and passive motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting.[14]
## Prognosis
A girl with a deformity of her right leg due to polio
Patients with abortive polio infections recover completely. In those who develop only aseptic meningitis, the symptoms can be expected to persist for two to ten days, followed by complete recovery.[63] In cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis will be permanent; cells that are not destroyed, but lose function temporarily, may recover within four to six weeks after onset.[63] Half the patients with spinal polio recover fully; one-quarter recover with mild disability, and the remaining quarter are left with severe disability.[64] The degree of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia, and inversely proportional to the degree of immunity.[35] Spinal polio is rarely fatal.[36]
Without respiratory support, consequences of poliomyelitis with respiratory involvement include suffocation or pneumonia from aspiration of secretions.[62] Overall, 5 to 10 percent of patients with paralytic polio die due to the paralysis of muscles used for breathing. The case fatality rate (CFR) varies by age: 2 to 5 percent of children and up to 15 to 30 percent of adults die.[1] Bulbar polio often causes death if respiratory support is not provided;[43] with support, its CFR ranges from 25 to 75 percent, depending on the age of the patient.[1][65] When intermittent positive pressure ventilation is available, the fatalities can be reduced to 15 percent.[66]
### Recovery
Many cases of poliomyelitis result in only temporary paralysis.[14] Generally in these cases, nerve impulses return to the paralyzed muscle within a month, and recovery is complete in six to eight months.[63] The neurophysiological processes involved in recovery following acute paralytic poliomyelitis are quite effective; muscles are able to retain normal strength even if half the original motor neurons have been lost.[67] Paralysis remaining after one year is likely to be permanent, although some recovery of muscle strength is possible up to 18 months after infection.[63]
One mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem and spinal cord motor neurons develop new branches, or axonal sprouts.[68] These sprouts can reinnervate orphaned muscle fibers that have been denervated by acute polio infection,[69] restoring the fibers' capacity to contract and improving strength.[70] Terminal sprouting may generate a few significantly enlarged motor neurons doing work previously performed by as many as four or five units:[37] a single motor neuron that once controlled 200 muscle cells might control 800 to 1000 cells. Other mechanisms that occur during the rehabilitation phase, and contribute to muscle strength restoration, include myofiber hypertrophy – enlargement of muscle fibers through exercise and activity – and transformation of type II muscle fibers to type I muscle fibers.[69][71]
In addition to these physiological processes, the body can compensate for residual paralysis in other ways. Weaker muscles can be used at a higher than usual intensity relative to the muscle's maximal capacity, little-used muscles can be developed, and ligaments can enable stability and mobility.[71]
### Complications
Residual complications of paralytic polio often occur following the initial recovery process.[13] Muscle paresis and paralysis can sometimes result in skeletal deformities, tightening of the joints, and movement disability. Once the muscles in the limb become flaccid, they may interfere with the function of other muscles. A typical manifestation of this problem is equinus foot (similar to club foot). This deformity develops when the muscles that pull the toes downward are working, but those that pull it upward are not, and the foot naturally tends to drop toward the ground. If the problem is left untreated, the Achilles tendons at the back of the foot retract and the foot cannot take on a normal position. Polio victims that develop equinus foot cannot walk properly because they cannot put their heel on the ground. A similar situation can develop if the arms become paralyzed.[72] In some cases the growth of an affected leg is slowed by polio, while the other leg continues to grow normally. The result is that one leg is shorter than the other and the person limps and leans to one side, in turn leading to deformities of the spine (such as scoliosis).[72] Osteoporosis and increased likelihood of bone fractures may occur. An intervention to prevent or lessen length disparity can be to perform an epiphysiodesis on the distal femoral and proximal tibial/fibular condyles, so that limb's growth is artificially stunted, and by the time of epiphyseal (growth) plate closure, the legs are more equal in length. Alternatively, a person can be fitted with custom made footwear which corrects the difference in leg lengths. Other surgery to re-balance muscular agonist/antagonist imbalances may also be helpful. Extended use of braces or wheelchairs may cause compression neuropathy, as well as a loss of proper function of the veins in the legs, due to pooling of blood in paralyzed lower limbs.[43][73] Complications from prolonged immobility involving the lungs, kidneys and heart include pulmonary edema, aspiration pneumonia, urinary tract infections, kidney stones, paralytic ileus, myocarditis and cor pulmonale.[43][73]
### Post-polio syndrome
Main article: Post-polio syndrome
Between 25 percent and 50 percent of individuals who have recovered from paralytic polio in childhood can develop additional symptoms decades after recovering from the acute infection,[74] notably new muscle weakness and extreme fatigue. This condition is known as post-polio syndrome (PPS) or post-polio sequelae.[75] The symptoms of PPS are thought to involve a failure of the oversized motor units created during the recovery phase of the paralytic disease.[76][77] Contributing factors that increase the risk of PPS include aging with loss of neuron units, the presence of a permanent residual impairment after recovery from the acute illness, and both overuse and disuse of neurons. PPS is a slow, progressive disease, and there is no specific treatment for it.[75] Post-polio syndrome is not an infectious process, and persons experiencing the syndrome do not shed poliovirus.[1]
## Epidemiology
This section needs to be updated. The reason given is: PMID 32584798. Please update this article to reflect recent events or newly available information. (October 2020)
See also: Poliomyelitis eradication
Reported polio cases in 2019'[78][79]
Country Wild
cases Circulating
vaccine-
derived
cases Transmission
status Type
Pakistan 146 22 endemic WPV1
cVDPV2
Afghanistan 29 0 endemic WPV1
Angola 0 129 cVDPV only cVDPV2
DRC 0 86 cVDPV only cVDPV2
CAR 0 19 cVDPV only cVDPV2
Ghana 0 18 cVDPV only cVDPV2
Nigeria 0 18 cVDPV only cVDPV2
Philippines 0 15 cVDPV only cVDPV1
cVDPV2
Ethiopia 0 12 cVDPV only cVDPV2
Chad 0 9 cVDPV only cVDPV2
Benin 0 8 cVDPV only cVDPV2
Togo 0 8 cVDPV only cVDPV2
Myanmar 0 6 cVDPV only cVDPV1
Somalia 0 3 cVDPV only cVDPV2
Malaysia 0 3 cVDPV only cVDPV1
Zambia 0 2 cVDPV only cVDPV2
Burkina Faso 0 1 cVDPV only cVDPV2
China 0 1 cVDPV only cVDPV2
Niger 0 1 cVDPV only cVDPV2
Yemen 0 3 cVDPV only cVDPV1
Total 175 365
The decade of the last recorded case of paralytic polio. Since the creation of this image, Nigeria has been certified free of wild polio as of August 2020.[80]
Following the widespread use of poliovirus vaccine in the mid-1950s, new cases of poliomyelitis declined dramatically in many industrialized countries. A global effort to eradicate polio began in 1988, led by the World Health Organization, UNICEF, and The Rotary Foundation.[81] These efforts have reduced the number of cases diagnosed each year by 99.9 percent; from an estimated 350,000 cases in 1988 to a low of 483 cases in 2001, after which it remained at a level of about 1,000–2000 cases per year for a number of years.[82][83]
In April 2012, the World Health Assembly declared that the failure to completely eradicate polio would be a programmatic emergency for global public health, and that it "must not happen."[84]
In 2015, polio was believed to remain naturally spreading in only two countries, Pakistan and Afghanistan,[85][86][87][88] although it continued to cause outbreaks in other nearby countries due to hidden or reestablished transmission.[89]
In 2015, cases decreased to 98 and further decreased in 2016 to 37 wild cases and 5 circulating vaccine-derived cases, but increased in 2019 to 175 wild cases and 365 circulating vaccine-derived cases.[79][90][91] Polio is one of only two diseases currently the subject of a global eradication program, the other being Guinea worm disease.[92] So far, the only diseases completely eradicated by humankind are smallpox, declared so in 1980,[93][94] and rinderpest, likewise in 2011.[95]
A concern is the presence of circulating vaccine-derived polioviruses. The oral polio vaccine is not perfect: while the genetic characteristics are carefully balanced to maximize efficacy and minimize virulence, it is possible for the polio virus in the oral vaccine to mutate. As a result, persons given the oral polio vaccine can acquire acute or chronic infections; or can transmit (circulate) mutated virus to other people. Circulating vaccine-derived poliovirus cases have exceeded wild-type cases, making it desirable to discontinue use of the oral polio vaccine as soon as safely possible.[96]
### Afghanistan and Pakistan
See also: Polio in Pakistan
The last remaining region with wild polio cases are the South Asian countries Afghanistan and Pakistan. Both major sides of the Afghan civil war support polio vaccination,[97] but after declining rapidly, polio rates are increasing in Afghanistan, with 19 cases in 2015,[86][98] 13 in 2016,[99] 14 in 2017,[79] 21 in 2018,[78] and 29 in 2019[78] out of a population of about 35 million.
In Pakistan, there were 53 cases in 2015 (out of a population of about 200 million) – the highest number for any country,[86][98] 20 in 2016,[99] 8 in 2017[79] 12 in 2018, and 146 in 2019.[78][100] Vaccination in Pakistan is hindered by conflict and organizational problems. The militant Pakistani Taliban claims vaccination is a Western plot to sterilise local children.[101] 66 vaccinators were killed in 2013 and 2014.[102][103] Cases dropped by 97 percent from 2014 to 2018;[104] reasons include 440 million dirham support from the United Arab Emirates to vaccinate more than ten million children,[103][105] changes in the military situation, and arrests of some of those who attacked polio workers.[101][106]
### Americas
The Americas were declared polio-free in 1994.[107] The last known case was a boy in Peru in 1991.[108]
### Western Pacific
In 2000 polio was declared to have been officially eliminated in 37 Western Pacific countries, including China and Australia.[109][110]
Despite eradication ten years before, an outbreak was confirmed in China in September 2011 involving a strain common in Pakistan.[111]
### Europe
Europe was declared polio-free in 2002.[112] On 1 September 2015, WHO confirmed two cases of circulating vaccine-derived poliovirus type 1 in Ukraine.[113]
### Southeast Asia
The last case of polio in the region was in India (part of the WHO's South-East Asia Region) in January 2011.[114] Since January 2011, there have been no reported cases of the wild polio infections in India, and in February 2012 the country was taken off the WHO list of polio endemic countries.[115][116]
On 27 March 2014 the WHO announced the eradication of poliomyelitis in the South-East Asia Region, which includes eleven countries: Bangladesh, Bhutan, North Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste.[85] With the addition of this region, 80 per cent of the world population was considered to be living in polio-free regions.[85]
However, in September 2019, the Department of Health of the Philippines declared a polio outbreak in the country after a 3-year-old girl was found with the disease on the 14th.[117][118]
In December 2019, acute poliomyelitis was confirmed in a 3-month-old infant in Tuaran, a town in Sabah state, Borneo, Malaysia.[119][120] It was the first confirmed case in Malaysia since 1992, and Malaysia had been declared polio-free in 2000. The child reportedly had a fever and muscle weakness, and although in stable condition, required assistance to breathe. Testing of the virus indicated that it was related to the strain that had appeared in the Philippines. Local officials said the strain originated from a weakened virus used in an oral vaccine that was then excreted in feces and spread into the unvaccinated population through unsanitary conditions.[119] It was reported that 23 of 199 children in the local community had not received the polio vaccine.[119]
### Middle East
In Syria difficulties in executing immunization programs in the ongoing civil war led to a return of polio, probably in 2012,[121] acknowledged by the WHO in 2013.[122][123] 15 cases were confirmed among children in Syria between October and November 2013 in Deir Ezzor. Later, two more cases, one each in rural Damascus and Aleppo, were identified. It was the first outbreak in Syria since 1999. Doctors and international public health agencies report more than 90 cases of polio in Syria, with fears of contagion in rebel areas from lack of sanitation and safe-water services.[124] In May 2014, the World Health Organization declared polio's renewed spread a world health emergency.[125][126]
A vaccination campaign in Syria operated literally under fire and led to the deaths of several vaccinators,[127] but returned vaccination coverage to pre-war levels.[128]
Another epidemic of polio was confirmed in 2017 in eastern Syria, probably resulting from a mutated form of the virus spreading through contaminated water.[129]
### Africa
Polio vaccination in Egypt
In 2003 in northern Nigeria – a country which at that time was considered provisionally polio free – a fatwa was issued declaring that the polio vaccine was designed to render children sterile.[130] Subsequently, polio reappeared in Nigeria and spread from there to several other countries. In 2013, nine health workers administering polio vaccine were targeted and killed by gunmen on motorcycles in Kano, but this was the only attack.[131][132] Local traditional and religious leaders and polio survivors worked to revive the campaign,[98] and Nigeria was removed from the polio-endemic list in September 2015 after more than a year without any cases,[133] only to be restored to the list in 2016 when two cases were detected.[134]
In 2013 the Center for Disease Control received reports of 183 cases of polio in Somalia, 14 in Kenya and 8 cases in the Somali Region of Ethiopia,[135] but Africa had no confirmed cases of wild poliovirus (WPV) since 2016.[136] Cases of circulating vaccine-derived poliovirus type 2 continue to appear in several countries.[137][138]
On 25 August 2020, the Africa Regional Certification Commission declared Africa free from wild polio.[139]
## History
See also: History of poliomyelitis and List of poliomyelitis survivors
An Egyptian stele thought to represent a polio victim, 18th Dynasty (1403–1365 BC)
The effects of polio have been known since prehistory; Egyptian paintings and carvings depict otherwise healthy people with withered limbs, and children walking with canes at a young age.[140] The first clinical description was provided by the English physician Michael Underwood in 1789, where he refers to polio as "a debility of the lower extremities".[141] The work of physicians Jakob Heine in 1840 and Karl Oskar Medin in 1890 led to it being known as Heine–Medin disease.[142] The disease was later called infantile paralysis, based on its propensity to affect children.
Before the 20th century, polio infections were rarely seen in infants before six months of age, most cases occurring in children six months to four years of age. Poorer sanitation of the time resulted in a constant exposure to the virus, which enhanced a natural immunity within the population. In developed countries during the late 19th and early 20th centuries, improvements were made in community sanitation, including better sewage disposal and clean water supplies. These changes drastically increased the proportion of children and adults at risk of paralytic polio infection, by reducing childhood exposure and immunity to the disease.[143]
Small localized paralytic polio epidemics began to appear in Europe and the United States around 1900.[144] Outbreaks reached pandemic proportions in Europe, North America, Australia, and New Zealand during the first half of the 20th century. By 1950, the peak age incidence of paralytic poliomyelitis in the United States had shifted from infants to children aged five to nine years, when the risk of paralysis is greater; about one-third of the cases were reported in persons over 15 years of age.[145] Accordingly, the rate of paralysis and death due to polio infection also increased during this time.[144] In the United States, the 1952 polio epidemic became the worst outbreak in the nation's history. Of the nearly 58,000 cases reported that year, 3,145 died and 21,269 were left with mild to disabling paralysis.[146] Intensive care medicine has its origin in the fight against polio.[147] Most hospitals in the 1950s had limited access to iron lungs for patients unable to breathe without mechanical assistance. Respiratory centers designed to assist the most severe polio patients, first established in 1952 at the Blegdam Hospital of Copenhagen by Danish anesthesiologist Bjørn Ibsen, were the precursors of modern intensive care units (ICU). (A year later, Ibsen would establish the world's first dedicated ICU.)[148]
The polio epidemics not only altered the lives of those who survived them, but also brought profound cultural changes, spurring grassroots fund-raising campaigns that would revolutionize medical philanthropy, and giving rise to the modern field of rehabilitation therapy. As one of the largest disabled groups in the world, polio survivors also helped to advance the modern disability rights movement through campaigns for the social and civil rights of the disabled. The World Health Organization estimates that there are 10 to 20 million polio survivors worldwide.[149] In 1977 there were 254,000 persons living in the United States who had been paralyzed by polio.[150] According to doctors and local polio support groups, some 40,000 polio survivors with varying degrees of paralysis were living in Germany, 30,000 in Japan, 24,000 in France, 16,000 in Australia, 12,000 in Canada and 12,000 in the United Kingdom in 2001.[149] Many notable individuals have survived polio and often credit the prolonged immobility and residual paralysis associated with polio as a driving force in their lives and careers.[151]
The disease was very well publicized during the polio epidemics of the 1950s, with extensive media coverage of any scientific advancements that might lead to a cure. Thus, the scientists working on polio became some of the most famous of the century. Fifteen scientists and two laymen who made important contributions to the knowledge and treatment of poliomyelitis are honored by the Polio Hall of Fame, which was dedicated in 1957 at the Roosevelt Warm Springs Institute for Rehabilitation in Warm Springs, Georgia, US. In 2008 four organizations (Rotary International, the World Health Organization, the U.S. Centers for Disease Control and UNICEF) were added to the Hall of Fame.[152][153]
World Polio Day (24 October) was established by Rotary International to commemorate the birth of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis. Use of this inactivated poliovirus vaccine and subsequent widespread use of the oral poliovirus vaccine developed by Albert Sabin led to establishment of the Global Polio Eradication Initiative (GPEI) in 1988. Since then, GPEI has reduced polio worldwide by 99 percent.[154]
### Etymology
The term derives from the Ancient Greek poliós (πολιός), meaning "grey", myelós (µυελός "marrow"), referring to the grey matter of the spinal cord, and the suffix -itis, which denotes inflammation,[12] i.e., inflammation of the spinal cord's grey matter, although a severe infection can extend into the brainstem and even higher structures, resulting in polioencephalitis, resulting in inability to breathe, requiring mechanical assistance such as an iron lung.
## Research
This section needs to be updated. Please update this article to reflect recent events or newly available information. (October 2020)
The Poliovirus Antivirals Initiative was launched in 2007 with the aim of developing antiviral medications for polio, but while several promising candidates were identified, none have progressed beyond Phase II clinical trials.[155][156] Pocapavir (a capsid inhibitor) and V-7404 (a protease inhibitor) may speed up viral clearance and are being studied for this purpose.[157]
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132. ^ "Nigeria marks one year without recorded polio case". BBC News. 24 July 2015. Archived from the original on 24 July 2015.
133. ^ "WHO Removes Nigeria from Polio-Endemic List". WHO. 26 September 2015. Archived from the original on 19 January 2016. Retrieved 8 January 2016.
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136. ^ "Where We Work - Nigeria". The Global Polio Eradication Initiative. 20 December 2015. Retrieved 20 December 2019.
137. ^ "Circulating vaccine-derived poliovirus in Mali". The Global Polio Eradication Initiative. 9 September 2015. Archived from the original on 14 September 2015. Retrieved 9 September 2015.
138. ^ Herriman R (25 May 2017). "Polio update: Two circulating vaccine-derived poliovirus type 2 outbreaks reported in Democratic Republic of the Congo". Outbreak News Today. Archived from the original on 25 May 2017. Retrieved 25 May 2017.
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140. ^ Paul JR (1971). A History of Poliomyelitis. Yale studies in the history of science and medicine. New Haven, Conn: Yale University Press. pp. 16–18. ISBN 978-0-300-01324-5.
141. ^ Underwood M (1789). "Debility of the lower extremities". A treatise on the diseases of children, with general directions for the management of infants from the birth (1789). 2. London: J. Mathews. pp. 88–91.
142. ^ Pearce JM (January 2005). "Poliomyelitis (Heine-Medin disease)". Journal of Neurology, Neurosurgery, and Psychiatry. 76 (1): 128. doi:10.1136/jnnp.2003.028548. PMC 1739337. PMID 15608013.
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144. ^ a b Trevelyan B, Smallman-Raynor M, Cliff AD (June 2005). "The Spatial Dynamics of Poliomyelitis in the United States: From Epidemic Emergence to Vaccine-Induced Retreat, 1910-1971". Annals of the Association of American Geographers. Association of American Geographers. 95 (2): 269–293. doi:10.1111/j.1467-8306.2005.00460.x. PMC 1473032. PMID 16741562.
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151. ^ Bruno RL (2002). The Polio Paradox: Understanding and Treating "Post-Polio Syndrome" and Chronic Fatigue. New York: Warner Books. pp. 105–06. ISBN 978-0-446-69069-0.
152. ^ Skinner W (15 November 2008). "Four added to Polio Hall of Fame at Warm Springs". The Times-Herald (Newnan, GA). Archived from the original on 28 March 2010. Retrieved 29 May 2009.
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156. ^ McKinlay MA, Collett MS, Hincks JR, et al. (November 2014). "Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication". The Journal of Infectious Diseases. 210 Suppl 1: S447-53. doi:10.1093/infdis/jiu043. PMID 25316866.
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## Further reading
External video
Presentation by David Oshinsky on Polio, June 21, 2006, C-SPAN
Presentation by Oshinsky on Polio, October 8, 2006, C-SPAN
* Kluger Jefferey (2004). Splendid Solution: Jonas Salk and the Conquest of Polio. New York: G. P. Putnam's Sons. ISBN 978-0-399-15216-0.
* Oshinsky DM (2005). Polio: An American story. Oxford: Oxford University Press. ISBN 978-0-19-515294-4. "polio."
* Shaffer MM, Bernard S (2005). The death of a disease: a history of the eradication of poliomyelitis. New Brunswick, N.J: Rutgers University Press. ISBN 978-0-8135-3677-4.
* Shell M (2005). Polio and its aftermath: the paralysis of culture. Cambridge: Harvard University Press. ISBN 978-0-674-01315-5. "polio."
* Wilson DJ (2005). Living with polio: the epidemic and its survivors. Chicago: University of Chicago Press. ISBN 978-0-226-90103-9.
* Wilson DJ, Silver J (2007). Polio voices: an oral history from the American polio epidemics and worldwide eradication efforts. New York: Praeger. ISBN 978-0-275-99492-1.
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*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Polio
|
c0032371
| 7,550 |
wikipedia
|
https://en.wikipedia.org/wiki/Polio
| 2021-01-18T19:00:16 |
{"gard": ["7413"], "mesh": ["D011051"], "umls": ["C0032371"], "orphanet": ["2912"], "wikidata": ["Q12195"]}
|
Myoclonus dystonia
Myoclonic dystonia or Myoclonus dystonia syndrome is a rare movement disorder that induces spontaneous muscle contraction causing abnormal posture. The prevalence of myoclonus dystonia has not been reported, however, this disorder falls under the umbrella of movement disorders which affect thousands worldwide.[1] Myoclonus dystonia results from mutations in the SGCE gene coding for an integral membrane protein found in both neurons and muscle fibers. Those suffering from this disease exhibit symptoms of rapid, jerky movements of the upper limbs (myoclonus), as well as distortion of the body's orientation due to simultaneous activation of agonist and antagonist muscles (dystonia).
Myoclonus dystonia is caused by loss-of-function-mutations in the epsilon sarcoglycan gene (SGCE). The disease is dominantly inherited, however SGCE is an imprinted gene,[2] so only the paternal allele is expressed. Therefore, children suffering from this disease inherit the mutation from the father. If the mutated allele is inherited from the mother, the child is not likely to exhibit symptoms.
While no cure has been found for myoclonus dystonia, treatment options are available to those suffering from the disease. Ethanol often ameliorates the symptoms well, and so the syndrome is also called "Alcohol-responsive dystonia". Alcohol may be substituted by benzodiazepines, such as clonazepam, which work through the same mechanism. Deep brain stimulation (DBS) is another viable option that can alleviate symptoms without the unwanted side effects of medications, and has been successful in treating other movement disorders.[3]
## Contents
* 1 Signs and symptoms
* 1.1 Myoclonus
* 1.2 Dystonia
* 1.3 Myoclonus dystonia
* 2 Cause
* 3 Treatment
* 3.1 Medications
* 3.1.1 Benzodiazepines
* 3.1.2 Antiepileptics
* 3.1.3 Anticholinergics
* 3.1.4 Botulinum toxin
* 3.2 Alcohol
* 3.3 Deep brain stimulation
* 4 References
* 5 External links
## Signs and symptoms[edit]
Myoclonus dystonia is characterized by two primary features: myoclonus and dystonia. For the majority of individuals with myoclonus dystonia, the myoclonus component of the disorder is often the primary and most disabling feature in comparison to the dystonia component. The symptoms of myoclonus dystonia vary substantially in severity.
### Myoclonus[edit]
Myoclonus is characterized by rapid contractions that affect the upper body including the neck, torso and arms, but may also affect the legs. These movements are stimulated by various factors including stress, noise, caffeine, and physical stimuli. Myoclonus can be characterized in multiple ways including neurological basis, muscular activity, and by stimuli. Myoclonus can be positive or negative; positive myoclonus results from brief spurts of muscle activity and negative myoclonus occurs when there is a lack of any muscular activity. Myoclonus is usually classified physiologically to optimize treatment. Myoclonus is a precursor effect to myoclonus dystonia and most commonly begins in childhood or adolescence.[4][5]
Myoclonus is classified as cortical, subcortical, peripheral or spinal. Cortical myoclonus is the most common of these four and affects the upper limbs and face. Myoclonus dystonia has been characterized under subcortical origin, specifically under nonsegmented myoclonus or brainstem myoclonus. Symptoms within this classification include the startle response and reticular reflex myoclonus. Sudden stimuli like noise or touch to areas around the head or chest cause the startle response which will go up the brain stem and down the spinal cord causing jerk-like movements. Hyperekplexia is a heightened brainstem response where an affected person will continue to elicit the same response to a repeated stimuli. In contrast, reticular reflex myoclonus occurs spontaneously to stimuli applied to distal limbs. Spinal myoclonus is caused by defects in spinal organization or connections, and peripheral myoclonus has symptoms of rhythmic jerks due to a neuron-the most common being the hemifacial spasm.[5]
### Dystonia[edit]
Dystonia is a response to simultaneous contraction of agonist and antagonist muscles seen as twisting and contorting that affect posture and stance. Other symptoms can include tremors and muscle spasms due to various interactions of muscle, contractions and movement.[4] Dystonia can be either primary or secondary with the latter being more common. Primary dystonia or "pure" dystonia is only physiological in origin. Secondary dystonia has multiple origins that are physiological, pathological or neurological.[6][7]
### Myoclonus dystonia[edit]
Myoclonus dystonia includes the rapid contractions of myoclonus alongside the abnormal postures classified under dystonia, as well as neurological and psychiatric issues. This disease typically begins during childhood with symptoms of myoclonus and slight dystonia, most commonly cervical dystonia or writer's cramp. Dystonia symptoms tend to not get exaggerated over the course of the disease and is rarely the only associated symptom, while the myoclonus symptoms can become more severe. Psychiatric issues are clinically diagnosed with the aforementioned symptoms and include depression, anxiety, personality disorders and addiction. Obsessive-compulsive disorder is associated with myoclonus dystonia as both have been found to have a commonality on chromosome 7 in various studies.[4]
Neurological symptoms are relatively common in those with myoclonus dystonia. Any neurological abnormalities will not normally be present in those affected at a young age. Neurological testing has been performed to determine the origins of these symptoms and multiple parts of the brain have been pinpointed including the brainstem, neocortex, pallidum, and thalamus. These cause various effects in those diagnosed with myoclonus dystonia including changes in posture and tremors, and very rarely dementia and ataxia.[4]
## Cause[edit]
The majority of myoclonus dystonia cases are the result of a mutation in the epsilon sarcoglycan gene (SGCE). This gene is found on chromosome 7, with its specific cytogenic location being 7q21.3. The 70,985 bp SGCE gene encodes the protein epsilon (ε)-sarcoglycan. The five proteins that make up the sarcoglycan family function as integral membrane proteins that anchor the cytoskeleton of cells to the extracellular matrix. Epsilon sarcoglycan is a membrane protein that can be found in the liver, lungs, kidney, and spleen, but is most prevalent in muscle and neuronal cells. Its prevalence in both muscle fibers and the synapses of neurons suggest why symptoms of both myoclonus and dystonia appear from the improperly functioning protein. Recessive mutations in the other sarcoglycans also result in muscular disorders, further supporting that mutations in the SGCE gene cause myoclonus dystonia.[8]
Epsilon sarcoglycan itself is part of the dystrophin-associated protein (DAP) complex that binds the sarcolemma of muscle cells to the extracellular connective tissue. The purpose is to reduce the mechanical force on the sarcolemma as a result of muscle contraction. In addition to myoclonus dystonia, problems associated with a dysfunctional DAP complex include Duchenne muscular dystrophy.[9]
Upwards of 65 mutations of the SGCE gene are thought to cause myoclonus dystonia. The majority of the mutations lead to a truncated protein product that results in the loss-of-function of the epsilon sarcoglycan protein.[10] The dysfunctional protein is ultimately recycled by the cell by degradation mediated by the proteasome, resulting in significant shortages of the integral membrane protein in both neurons and muscle fibers.
The mutant allele is inherited in a dominant fashion—that is the mutation can be inherited if one parent has that allele. However, genomic imprinting occurs on the mother's allele, so only the father's allele is expressed.[2][10] Therefore, inheriting a mutated, paternal allele of the SGCE gene will result in the expression of the dysfunctional epsilon sarcoglycan protein. Offspring will not produce a mutant protein product in 95% of cases where the mother passes on a mutation in the SGCE gene.[10]
While SGCE gene mutations are the central cause of myoclonus dystonia, there have been separate cases where individuals and families present symptoms akin to myoclonus dystonia but lack the mutations at this locus. Base-pair deletions of the DYT1 gene, missense mutations in the DRD2 gene, maternal uniparental disomy, and chromosome 18 linkage have all been associated in rare cases myoclonus dystonia where the SGCE gene is unaffected.[4]
## Treatment[edit]
To date, there is no single, universal treatment that has been found to cure myoclonus dystonia. However, there are several treatment methods that have been found to be effective for helping to reduce the symptoms associated with the syndrome.
### Medications[edit]
Many drugs used to treat myoclonus dystonia do not have a significant impact individually, but when combined, can work on different brain mechanisms to best alleviate symptoms. The method of treatment used depends on the severity of the symptoms presented in the individual, and whether the underlying cause of the syndrome is known.
#### Benzodiazepines[edit]
Benzodiazepines such as clonazepam improve tremors caused by the myoclonus aspect of this syndrome by binding allosterically to GABAA ionotropic receptors, causing an influx of chloride ions that produce an inhibitory effect that can calm myoclonic jerks.[4][11]
#### Antiepileptics[edit]
Antiepileptics like valproate must act upon GABA receptors and manipulate ionic conductance to reduce tremors and spasms in myoclonus dystonia. GABA neurons that fire rapidly and affect the motor cortex are blocked by antiepileptics in addition to changes in sodium and calcium concentrations that can excite the neuron. Different antiepileptics vary in sufficiency to control ionic conductance and can also produce seizures or myoclonus symptoms in some patients.[12] Another agent that has been used is zonisamide.[13]
#### Anticholinergics[edit]
Anticholinergics like benzatropine alleviate dystonia symptoms by blocking the activity of acetylcholine. Acetylcholine is involved in the pathophysiology of dystonia within the basal ganglia, although its exact role has not been determined. Acetylcholine is involved with dopamine and glutamate pathways in the basal ganglia, in addition to presynaptic muscarinic receptors which are involved in motor control. Acetylcholine is usually overactive in dystonia patients and blocking of this neurotransmitter would reduce contortion of the upper body, but can produce side effects of drowsiness, confusion and memory issues in adults.[14]
#### Botulinum toxin[edit]
Botulinum toxin injections also act upon acetylcholine to reduce dystonia symptoms. The neurotoxin is active in presynaptic terminals and blocks exocytosis of acetylcholine into the synaptic cleft which reduces muscle activity. Botulinum may also have a role in inhibiting glutamate and changing muscle movement. Studies have also shown possible axon transport of this neurotoxin as well as its function as a pain reliever without effect on overactive muscle movement in myoclonus dystonia patients.[15]
### Alcohol[edit]
Consumption of alcohol has also been found to be an effective agent for temporarily easing the severity of the tremors associated with myoclonus dystonia. Alcohol causes an increase in GABA transmission between interneurons and Purkinje cells. This then reduces the transmission of glutamate at granule cell-Purkinje cell synapses, which decreases muscle movements. This treatment only alleviates the strength of the tremors for a short duration and does not change how often tremors will occur. Doctors inform patients of risks associated with the use of alcohol for myoclonus dystonia due to the high susceptibility for alcohol abuse and dependency. Alcoholism itself causes tremors in the hands and degeneration of the Purkinje cells and other parts of the cerebral cortex, counteracting alcohol's original corrective effects.[16]
### Deep brain stimulation[edit]
Diagram of Deep Brain Stimulation on a patient. This is a common treatment option for movement disorders that has shown to be successful in alleviating symptoms. [17]
Deep brain stimulation (DBS) has been found to be an effective and safe treatment for myoclonus dystonia patients, whose severe and debilitating symptoms are resistant to drug treatments. Electrical stimulation within the brain is a common treatment for many movement disorders because of the ability to excite or inhibit neurons within the brain. Deep brain stimulation patients have electrodes inserted into the brain and then an electrical signal is sent from an external source to elicit a response. The frequency and intensity of this signal can be changed to monitor the effects on neuronal activity using voltage recordings or neuroimaging, like functional MRIs. By re-positioning the electrodes in different areas or changing the size or timing of the stimulus, varying effects can be seen on the patient depending on the origin of the disorder.[3]
In one study, five patients with genetically determined epsilon sarcoglycan protein deficiency underwent deep brain stimulation of the internal pallidum. Each patient's movement and disability symptoms were assessed before and after treatment using the Burke-Fahn-Marsden Dystonia Rating Scale and the Unified Myoclonus Rating Scale. Upon completion of the surgery, both the myoclonus and dystonia symptoms of the disorder had decreased by 70%, with no report of unfavorable side effects. Therefore, deep brain stimulation has been shown to effectively improve both myoclonus and dystonia, unlike many drug treatments which may improve one or the other.[17]
Other studies examined the effects of DBS to both the ventrointermediate nucleus of the thalamus, Vim, and the globus pallidus interna, GPi. Following deep brain stimulation of GPi and Vim, the Unified Myoclonus Rating Scale disability score improved 61-66%. In addition, the Dystomia Rating Scale score improved by 45-48%. While there was no significant difference in improvement between GPi-Vim stimulation and GPi stimulation, GPi-Vim stimulation was significantly more effective than Vim deep brain stimulation alone. Overall, Deep brain stimulation shows promise as a viable treatment for myoclonus dystonia.[18]
Although myoclonus and dystonia are present in myoclonus dystonia patients, optimum treatment for myoclonus dystonia differs from the treatment for myoclonus or dystonia alone. Myoclonus improved significantly more than dystonia when Deep brain stimulation was applied. In addition, myoclonus improved regardless of whether Deep brain stimulation was applied to GPi or Vim. However, GPi stimulation was more effective at reducing the symptoms of dystonia than Vim stimulation.[17]
## References[edit]
1. ^ Wenning, Gregor K.; Kiechl, Stefan; Seppi, Klaus; Müller, Joerg; Högl, Birgit; Saletu, Michael; Rungger, Gregor; Gasperi, Arno; Willeit, Johann; Poewe, Werner (1 December 2005). "Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study". The Lancet. Neurology. 4 (12): 815–820. doi:10.1016/S1474-4422(05)70226-X. PMID 16297839.
2. ^ a b Grabowski M, Zimprich A, Lorenz-Depiereux B, et al. (February 2003). "The epsilon-sarcoglycan gene (SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted". Eur. J. Hum. Genet. 11 (2): 138–44. doi:10.1038/sj.ejhg.5200938. PMID 12634861.
3. ^ a b Kringelbach, Morten L.; Jenkinson, Ned; Owen, Sarah L. F.; Aziz, Tipu Z. (2007-08-01). "Translational principles of deep brain stimulation". Nature Reviews Neuroscience. 8 (8): 623–635. doi:10.1038/nrn2196. ISSN 1471-003X. PMID 17637800.
4. ^ a b c d e f Raymond, Deborah; Ozelius, Laurie (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Myoclonus-Dystonia. Seattle (WA): University of Washington, Seattle. PMID 20301587.
5. ^ a b Kojovic, Maja; Cordivari, Carla; Bhatia, Kailash (2011-01-01). "Myoclonic disorders: a practical approach for diagnosis and treatment". Therapeutic Advances in Neurological Disorders. 4 (1): 47–62. doi:10.1177/1756285610395653. ISSN 1756-2856. PMC 3036960. PMID 21339907.
6. ^ Spatola, Marianna; Wider, Christian (2012-01-01). "Overview of primary monogenic dystonia". Parkinsonism & Related Disorders. 18 Suppl 1: S158–161. doi:10.1016/S1353-8020(11)70049-9. ISSN 1873-5126. PMID 22166420.
7. ^ Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; DeLong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, H.A. (2013-06-15). "Phenomenology and classification of dystonia: a consensus update". Movement Disorders. 28 (7): 863–873. doi:10.1002/mds.25475. ISSN 0885-3185. PMC 3729880. PMID 23649720.
8. ^ Hack, A. A.; Groh, M. E.; McNally, E. M. (2000-02-01). "Sarcoglycans in muscular dystrophy". Microscopy Research and Technique. 48 (3–4): 167–180. doi:10.1002/(SICI)1097-0029(20000201/15)48:3/4<167::AID-JEMT5>3.0.CO;2-T. ISSN 1059-910X. PMID 10679964.
9. ^ Ervasti, James M. (2013-01-01). "Structure and Function of the Dystrophin-Glycoprotein Complex". Madame Curie Bioscience Database.
10. ^ a b c "SGCE gene". Genetics Home Reference. 2016-03-28. Retrieved 2016-04-07.
11. ^ Rudolph, Uwe; Möhler, Hanns (1 February 2006). "GABA-based therapeutic approaches: GABAA receptor subtype functions". Current Opinion in Pharmacology. 6 (1): 18–23. doi:10.1016/j.coph.2005.10.003. PMID 16376150.
12. ^ Caviness, John N. (2014-01-01). "Treatment of Myoclonus". Neurotherapeutics. 11 (1): 188–200. doi:10.1007/s13311-013-0216-3. ISSN 1933-7213. PMC 3899494. PMID 24037428.
13. ^ Salamon A, Zádori D, Horváth E, Vécsei L, Klivényi P (2019) Zonisamide treatment in myoclonus-dystonia. Orv Hetil 160(34):1353-1357
14. ^ Eskow Jaunarajs, K. L.; Bonsi, P.; Chesselet, M. F.; Standaert, D. G.; Pisani, A. (2015-04-01). "Striatal cholinergic dysfunction as a unifying theme in the pathophysiology of dystonia". Progress in Neurobiology. 127–128: 91–107. doi:10.1016/j.pneurobio.2015.02.002. PMC 4420693. PMID 25697043.
15. ^ Oh, Hyun-Mi; Chung, Myung Eun (2015-08-14). "Botulinum Toxin for Neuropathic Pain: A Review of the Literature". Toxins. 7 (8): 3127–3154. doi:10.3390/toxins7083127. ISSN 2072-6651. PMC 4549742. PMID 26287242.
16. ^ Deik, Andres; Saunders-Pullman, Rachel; Luciano, Marta San (2012-09-01). "Substances of abuse and movement disorders: complex interactions and comorbidities". Current Drug Abuse Reviews. 5 (3): 243–253. doi:10.2174/1874473711205030243. ISSN 1874-4737. PMC 3966544. PMID 23030352.
17. ^ a b c Azoulay-Zyss, Julie; Roze, Emmanuel; Welter, Marie-Laure; Navarro, Soledad; Yelnik, Jérôme; Clot, Fabienne; Bardinet, Eric; Karachi, Carine; Dormont, Didier; Galanaud, Damien; Pidoux, Bernard; Cornu, Philippe; Vidailhet, Marie; Grabli, David (1 January 2011). "Bilateral deep brain stimulation of the pallidum for myoclonus-dystonia due to ε-sarcoglycan mutations: A pilot study". Archives of Neurology. 68 (1): 94–98. doi:10.1001/archneurol.2010.338. PMID 21220679.
18. ^ Smith, Kara M.; Spindler, Meredith A. (2015-02-02). "Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders". Tremor and Other Hyperkinetic Movements. 5: 278. doi:10.7916/D84X56HP. ISSN 2160-8288. PMC 4314611. PMID 25713746.
## External links[edit]
Classification
D
* OMIM: 159900
* DiseasesDB: 31321
* SNOMED CT: 439732004
External resources
* GeneReviews: Myoclonus Dystonia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Myoclonic dystonia
|
c1834570
| 7,551 |
wikipedia
|
https://en.wikipedia.org/wiki/Myoclonic_dystonia
| 2021-01-18T18:50:02 |
{"mesh": ["C536096"], "orphanet": ["36899"], "wikidata": ["Q3710440"]}
|
The premycotic phase is a phase of mycosis fungoides in which a patient has areas of red, scaly, itchy skin on areas of the body that are usually not exposed to sun. This is early-phase mycosis fungoides, but it is hard to diagnose the rash as mycosis fungoides during this phase. The premycotic phase may last from months to decades.
## References[edit]
* Premycotic phase entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
This 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
|
Premycotic phase
|
None
| 7,552 |
wikipedia
|
https://en.wikipedia.org/wiki/Premycotic_phase
| 2021-01-18T18:54:00 |
{"wikidata": ["Q7240516"]}
|
X-linked hypophosphatemia (XLH) is an inherited disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (rickets). XLH is usually diagnosed in childhood. Features include bowed or bent legs, short stature, bone pain, and severe dental pain. XLH is caused by mutations in the PHEX gene on the X chromosome, and inheritance is X-linked dominant. Treatment generally involves supplements of phosphate and high-dose calcitriol (the active form of Vitamin D), and may also include growth hormones, corrective surgery, and dental treatment. The long-term outlook varies depending on severity and whether complications arise. While some adults with XLH may have minimal medical problems, others may experience persistant discomfort or complications.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked hypophosphatemia
|
c0733682
| 7,553 |
gard
|
https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia
| 2021-01-18T17:57:03 |
{"mesh": ["D053098"], "omim": ["307800"], "orphanet": ["89936"], "synonyms": ["X-linked hypophosphatemic rickets", "XLH", "Hypophosphatemic rickets, X-linked dominant", "Hypophophatemia, X-linked", "Vitamin D-Resistant Rickets, X-linked", "Hypophophatemic vitamin D-resistant rickets", "HPDR"]}
|
In a family with several cases of Hashimoto struma, DeGroot et al. (1962) demonstrated an abnormal, small, iodinated protein in the serum and suggested that a defect in thyroid basement membrane may account for the appearance of this protein in the blood. Three sibs, their father, and their paternal aunt were affected. The paternal grandparents were dead. Hall et al. (1962) presented data that they felt supported autosomal dominant inheritance of the tendency to thyroid autoimmunity. Hall et al. (1964) studied 6 families in which the father had thyroid autoantibody and the mother did not. In each case female children had thyroid autoantibodies. Transplacental transmission was thus ruled out and genetic transmission was suggested. Volpe et al. (1963) also found an impressive familial aggregation. Masi et al. (1964) found examples of mother-daughter, father-daughter, 3 sisters, and 2 sisters with Hashimoto struma. See review of Masi et al. (1965).
Matsuura et al. (1980) described familial neonatal transient hypothyroidism in the offspring of a mother with Hashimoto thyroiditis. They attributed the disorder in the infants to transplacental passage of maternal TSH-binding inhibitor immunoglobulins. Leung (1985) reported a family in which the mother and 3 offspring had 'hashitoxic' periodic paralysis, i.e., Hashimoto thyroiditis, thyrotoxicosis, and periodic paralysis (see 188580). Conaway et al. (1985) observed familial aggregation of lymphocytic thyroiditis in borzoi dogs. They suggested autosomal recessive inheritance. Shuper et al. (1987) found renal impairment in a 12-year-old boy and his 2 sisters, all of whom had Hashimoto thyroiditis. Three generations of the family had autoimmune thyroid disease. Proteinuria disappeared in all 3 children during the 3.5 years of follow-up.
Phillips et al. (1990) found that autoantibodies to thyroid peroxidase (TPO; 606765) were inherited as a dominant mendelian trait in females, with reduced penetrance in males. Similar results were obtained with thyroglobulin autoantibodies. Genetic linkage to HLA (see 142800) was excluded. Because of potential bias in the study carried out in families with autoimmune thyroid disease, Phillips et al. (1991) studied the inheritance of thyroid autoantibodies in 49 families unselected for autoimmune thyroid disease. Among 24 families with facioscapulohumeral muscular dystrophy, 10 with Friedreich ataxia, and 15 with schizophrenia, the prevalence rates of TPO and thyroglobulin antibodies were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families in which one or more individuals had one or both of the autoantibodies, segregation analysis supported mendelian dominant inheritance in women but not in men.
The interaction of FAS (134637) with its ligand, FASL (134638), regulates a number of physiologic and pathologic processes of cell death. Giordano et al. (1997) noted that triggering of FAS contributes to the regulation of the immune response and tissue homeostasis, as well as to the immunologic clearance of virus or tumor cells. Hashimoto thyroiditis is an autoimmune disorder in which destructive processes overcome the potential capacity of thyroid replacement, estimated as about 5- to 10-fold in a life time. Apoptosis has been occasionally observed in histologic sections of normal thyroid; however, apoptotic cell death is abnormally accelerated during the pathologic phases, leading to clinical hypothyroidism in HT. Giordano et al. (1997) demonstrated that thyrocytes from HT glands, but not from nonautoimmune thyroids, express FAS. Interleukin-1-beta (147720), abundantly produced in HT glands, induced FAS expression in normal thyrocytes, and crosslinking of FAS resulted in massive thyrocyte apoptosis. The ligand for FAS was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill FAS-sensitive targets. Exposure to IL-1-beta induced thyrocyte apoptosis, which was prevented by antibodies that block FAS, suggesting to Giordano et al. (1997) that IL-1-beta-induced FAS expression serves as a limited factor for thyrocyte destruction. Thus, FAS-FASL interactions among HT thyrocytes may contribute to clinical hypothyroidism.
Interferon-gamma (IFNG; 147570) had been implicated with contradictory results in the pathogenesis of autoimmune (Hashimoto) thyroiditis, the third most prevalent autoimmune disease in the United States (Jacobson et al., 1997) and the most frequent cause of hypothyroidism in adults (Weetman, 1998). To test whether the local production of IFN-gamma can lead to thyroid dysfunction, Caturegli et al. (2000) generated transgenic mice that express constitutive Ifng in thyroid follicular cells. This expression resulted in severe hypothyroidism, with growth retardation and disruption of the thyroid architecture. The hypothyroidism derived from a profound inhibition of the expression of the sodium-iodide symporter gene.
Ochi et al. (2002) identified alpha-enolase (ENO1; 172430) as the autoantigen in Hashimoto encephalopathy, a rare autoimmune disease associated with Hashimoto thyroiditis.
The autoimmune thyroid diseases (AITDs) include Hashimoto thyroiditis and Graves disease (GRD; 275000). In both Graves disease and Hashimoto thyroiditis, thyroid-reactive T cells are formed and infiltrate the thyroid gland. Tomer et al. (1999) performed a whole-genome linkage study of a dataset of 56 multiplex, multigenerational AITD families (354 individuals) using 387 microsatellite markers. They identified 6 loci that showed evidence for linkage to AITD. Only one locus, on chromosome 6 (AITD1; 80 cM) was linked with both. This locus was close to, but distinct from, the HLA region. One locus on chromosome 13 (HT1; 96 cM) was linked to HT (maximum lod score, 2.1), and another locus on chromosome 12 (HT2; 97 cM) was linked to HT in a subgroup of the families (maximum lod score, 3.8). Three loci showed evidence for linkage with GRD: GD1 on chromosome 14 (99 cM; maximum lod score, 2.5), GD2 on chromosome 20 (56 cM; maximum lod score, 3.5), and GD3 on chromosome X (114 cM; maximum lod score, 2.5). Since GD2 showed the strongest evidence for linkage to GRD, they fine-mapped this locus to a 1-cM interval between markers at 55 and 56 cM on chromosome 20. The authors concluded that GRD and Hashimoto thyroiditis are genetically heterogeneous, with only one locus in common to both diseases on chromosome 6; that only one HT locus was identified in all families, probably due to heterogeneity of the HT phenotype; and 3 loci were shown to induce genetic susceptibility to GRD by interacting with each other. One of them, GD2, was fine-mapped to a 1-cM interval.
Sakai et al. (2001) undertook a genomewide analysis of 123 Japanese sib pairs affected with AITD. At 19 regions on 14 chromosomes, the multipoint maximum lod score was greater than 1. Chromosome 5q31-q33 yielded suggestive evidence for linkage to AITD as a whole, with a maximum lod score of 3.14 at marker D5S436, and chromosome 8q23-q24 yielded suggestive evidence for linkage to HT, with a maximum lod score of 3.77 at marker D8S272.
Akamizu et al. (2003) performed an association study using 6 microsatellite markers situated at or near the 5q31-q33 locus associated with AITD in a set of 440 unrelated Japanese AITD patients and 218 Japanese controls. They found significant allelic association between AITD and 3 markers located in 5q23-q33. Graves disease demonstrated significant associations with 2 of these markers, while Hashimoto thyroiditis did not show significant associations with any markers. When patients with Graves disease were stratified according to clinical manifestations, the association was significantly different from the other subgroup of each category.
Fetal microchimerism, the engraftment of fetal progenitor cells into maternal tissues, has been implicated in the etiology of autoimmune diseases. Klintschar et al. (2001) used PCR analysis to determine whether microchimerism occurred in thyroid gland specimens from female Hashimoto thyroiditis patients. Using primers unique to a Y-chromosomal sequence (SRY; 480000) and primers for a sequence that is Y/X-chromosomal homologous except for a 6-bp deletion in the X-chromosomal sequence (amelogenin; 300391), Klintschar et al. (2001) detected microchimerism in 8 of 17 Hashimoto patients, but in only 1 of 25 controls (nodular goiters). Both groups were of similar age and had comparable numbers of pregnancies and numbers of sons. The authors concluded that microchimerism is significantly more common in Hashimoto patients than in patients suffering from nodular goiter. They suggested that microchimerism might play a role in the development of Hashimoto disease, although they cannot completely exclude that microchimerism is just an 'innocent bystander' in a process triggered by other mechanisms.
Generalized vitiligo (see 606579) is a common autoimmune disorder in which patchy loss of skin and hair pigmentation results from loss of pigment-forming melanocytes from the involved regions. Alkhateeb et al. (2002) studied a 3-generation family in which vitiligo and Hashimoto thyroiditis occurred in numerous individuals. A genomewide scan of 24 family members, including 14 affected with autoimmune disease, revealed linkage of an oligogenic autoimmune susceptibility locus, termed AIS1 (607836), to a 14.4-cM interval at chromosome 1p32.2-p31.3 (multipoint lod score = 2.90). A 2-locus analysis of Hashimoto thyroiditis in family members segregating an AIS1 susceptibility allele showed suggestive linkage to markers in chromosome 6p22.3-q14.1 (affecteds-only multipoint lod score = 1.52), in a region spanning both the major histocompatibility complex and AITD1 (Tomer et al., 1999). The authors concluded that the 1p AIS1 locus is associated with susceptibility to autoimmunity, particularly vitiligo, in this family, and that a chromosome 6 locus, most likely AITD1, may mediate the occurrence of Hashimoto thyroiditis in AIS1-susceptible family members.
Ueda et al. (2003) identified polymorphisms of the CTLA4 gene (123890) as candidates for primary determinants of risk for the common autoimmune disorders Graves disease (275000), autoimmune hypothyroidism, and type I diabetes (see 222100 and 601388). In humans, disease susceptibility was mapped to a noncoding 6.1-kb 3-prime region of CTLA4, the common allelic variation of which (see 123890.0002) was correlated with lower mRNA levels of the soluble alternative splice form of CTLA4. In a mouse model of type I diabetes, susceptibility was also associated with variation in CTLA4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80 (112203)/CD86 (601020) ligand-binding domain.
Criswell et al. (2005) determined that the R620W functional SNP in PTPN22 (600716.0001) conferred risk of 4 separate autoimmune phenotypes (type 1 diabetes, 222100; rheumatoid arthritis, 180300, systemic lupus erythematosus, 152700; and Hashimoto thyroiditis) in a collection of 265 multiplex families assembled by the Multiple Autoimmune Disease Genetics Consortium (MADGC). In each of these families, at least 2 of the 9 'core' autoimmune diseases were present.
Allen et al. (2003) studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. They found AITD, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. They performed a genomewide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. They observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (lod, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428); Sakai et al. (2001) had also found linkage to the long arm of chromosome 5 in their study of Japanese sib pairs with AITD-hypothyroidism. AITD-hypothyroidism showed a more modest linkage peak to the same region (lod, 1.46; P = 0.005). The authors concluded that a gene on chromosome 5q11.2-q14.3 is likely to contribute to susceptibility to AITD in the Amish.
Vaidya et al. (2002) reviewed the genetics of AITD including hyperthyroid Graves disease, Hashimoto (goitrous) thyroiditis, atrophic autoimmune hypothyroidism, postpartum thyroiditis, and thyroid-associated orbitopathy (TAO). These different manifestations of AITD may occur synchronously, most frequently as the combination of Graves disease and TAO. Together, AITDs are the commonest autoimmune disorders in the population, affecting between 2 and 4% of women and up to 1% of men. Furthermore, AITD prevalence increases with advancing age, with more than 10% of subjects over 75 years of age having biochemical evidence of mild (subclinical) hypothyroidism, the majority of which is due to autoimmune disease. They reviewed the associations of AITD with other autoimmune disorders, monogenic and chromosomal disorders that have AITD as a component, and AITDs as complex genetic traits. Additionally they reviewed the relationship of HLA (see 142800) and MHC-linked genes with AITD, particularly with Graves disease, and the association of the CTLA4 gene and its polymorphisms with Graves disease and AITD.
Tomer et al. (2003) performed a whole-genome linkage study in an expanded dataset of 102 multiplex families with AITD (540 individuals), using 400 microsatellite markers. Seven loci showed evidence for linkage to AITD (either Graves disease or Hashimoto thyroiditis). Three loci, on chromosomes 6p (AITD1; 608173), 8q (AITD3; 608175), and 10q (AITD4; 608176), showed evidence for linkage with both Graves disease and Hashimoto thyroiditis (maximum multipoint heterogeneity lod scores (hlod) 2.0, 3.5, and 4.1, respectively). Three loci showed evidence for linkage with Graves disease: on 7q, 14q, and 20q. One locus on 12q showed evidence of linkage with Hashimoto thyroiditis, giving an hlod of 3.4. Comparison with the results obtained in an earlier dataset showed that the 20q locus (GRD2; 603388) and the 12q locus (Hashimoto thyroiditis 2; HT2) continued to show evidence for linkage in the expanded dataset. The results demonstrated that multiple genes may predispose to both Graves disease and Hashimoto thyroiditis and that some may be common to both diseases and some unique. The loci that continue to show evidence for linkage in the expanded dataset represent serious candidate regions for gene identification.
Kacem et al. (2003) analyzed polymorphic microsatellite markers around the SLC26A4 gene (605646), which encodes pendrin, an apical transporter of iodide to the thyroid, to investigate the role of SLC26A4 in the genetic control of AITDs. Using case-control and family-based designs in a sample from Tunisia, Kacem et al. (2003) found evidence that SLC26A4 may be a susceptibility gene for AITDs, with varying contributions in Graves disease and Hashimoto thyroiditis.
Barbero et al. (2004) described 3 patients with choanal atresia (608911) whose mothers received methimazole during pregnancy for the treatment of thyrotoxicosis (Graves disease and Hashimoto thyroiditis).
Shirasawa et al. (2004) used linkage and association analyses of over 500 autoimmune thyroiditis patients and controls to identify a novel zinc finger gene, designated ZFAT1 (610931), as a susceptibility gene at 8q23-q24. The T allele of the SNP Ex9b-SNP10 (610931.0001) was associated with increased risk for AITD (dominant model: odds ratio = 1.7, P = 0.00009). The authors suggested that Ex9b-SNP10 may play a critical role in B cell function by affecting the expression level of a truncated ZFAT1 splice variant through regulating expression of a small antisense transcript, and that this regulatory mechanism of SNPs might be involved in controlling susceptibility or resistance to human disease.
Using FISH, Invernizzi et al. (2005) assessed the presence of monosomy X in women with systemic sclerosis (SSC; 181750) or AITD and age-matched healthy women. The rate of monosomy X increased with age in all 3 groups, but it was significantly higher for women with SSC or AITD. Monosomy X was more frequent in peripheral T and B lymphocytes than in other blood cell populations, and there was no evidence of male fetal microchimerism. Invernizzi et al. (2005) proposed that chromosome instability is common to women with these autoimmune diseases and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance in autoimmune disease.
Endocrine \- Hashimoto thyroiditis Immunology \- Thyroid autoimmunity Lab \- Hashimoto struma \- Thyroid autoantibodies \- Abnormal, small, iodinated protein in the serum \- Defect in thyroid basement membrane 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
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HASHIMOTO THYROIDITIS
|
c0677607
| 7,554 |
omim
|
https://www.omim.org/entry/140300
| 2019-09-22T16:40:26 |
{"mesh": ["D050031"], "omim": ["140300"], "icd-9": ["245.2"], "icd-10": ["E06.3"], "synonyms": ["Alternative titles", "HT", "HASHIMOTO STRUMA", "HYPOTHYROIDISM, AUTOIMMUNE"]}
|
Congenital insensitivity to pain with severe intellectual disability is a rare autosomal recessive hereditary sensory and autonomic neuropathy characterized by the complete absence of pain perception from birth, an unresponsiveness to soft touch, severe non-progressive cognitive delay, and normal motor movement/behavior and strength. Affected cases retained hot and cold perception.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenital insensitivity to pain with severe intellectual disability
|
None
| 7,555 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=453510
| 2021-01-23T17:12:15 |
{"synonyms": ["Congenital absence of pain with severe intellectual disability", "Congenital analgesia with severe intellectual disability", "Congenital insensitivity to pain with preserved temperature sensation", "Congenital insensitivity to pain with severe non-progressive cognitive delay"]}
|
For a discussion of genetic heterogeneity of coronary heart disease (CHD), see 607339.
Clinical Features
Engert et al. (2008) studied 133 affected and 187 unaffected individuals from 50 French Canadian families with early-onset coronary heart disease, descended from a founder population in the Saguenay-Lac-Saint-Jean region of Quebec. Probands had at least 50% stenosis in at least 2 coronary arteries before the age of 62 or 66 years for men and women, respectively; patients with familial hypercholesterolemia or with family members known to be homozygous for mutations in the lipoprotein lipase gene (LPL; 609708) were excluded.
Mapping
Engert et al. (2008) performed a genomewide scan on 119 affected and 165 unaffected individuals from 42 French Canadian families with early-onset coronary heart disease and obtained a nonparametric linkage score of 3.14 (p = 0.001) at D8S1106 on chromosome 8p22. The authors performed fine mapping on an enlarged sample of 50 families with 320 individuals and found evidence of linkage at D8S552 (NPL score = 3.53; p = 0.00033), a marker mapping to the same location as D8S1106. Engert et al. (2008) analyzed 10 candidate genes in the region, including the LPL gene, located 13 cM from the peak, but did not identify a disease-associated mutation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CORONARY HEART DISEASE, SUSCEPTIBILITY TO, 9
|
c2677580
| 7,556 |
omim
|
https://www.omim.org/entry/612030
| 2019-09-22T16:02:25 |
{"omim": ["612030"]}
|
A number sign (#) is used with this entry because of evidence that cerebrooculofacioskeletal syndrome-1 (COFS1) is caused by homozygous or compound heterozygous mutation in the ERCC6 gene (609413) on chromosome 10q11.
Cockayne syndrome type B (CSB; 133540) is an allelic disorder.
Description
Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010).
### Genetic Heterogeneity of Cerebrooculofacioskeletal Syndrome
See also COFS2 (610756), caused by mutation in the ERCC2 gene (126340); COFS3 (616570), caused by mutation in the ERCC5 gene (133530); and COFS4 (610758), caused by mutation in the ERCC1 gene (126380).
Clinical Features
Pena and Shokeir (1974) observed 10 patients in 3 kindreds with a syndrome comprised of microcephaly, hypotonia, failure to thrive, arthrogryposis, eye defects, prominent nose, large ears, overhanging upper lip, micrognathia, widely set nipples, kyphoscoliosis, and osteoporosis. The first 2 kindreds were American Indian with French admixture and much consanguinity in the first of these. Preus and Fraser (1974) described a single case in an offspring of first-cousin parents of Italian extraction. One of Pena and Shokeir's affected sibships (2 affected out of 6 children) had brother-sister parents. Surana et al. (1978) described COFS syndrome in a black American infant.
Lerman-Sagie et al. (1987) described an infant with COFS manifestations plus radiologic and pathologic findings of osteopetrosis and severe degeneration of skeletal muscles. The muscular changes appeared to be the cause of the flexion contractures present at birth. Gershoni-Baruch et al. (1991) reported the case of an infant born of first-cousin parents who had findings of congenital muscular dystrophy. Laugel et al. (2008) questioned the diagnosis of COFS in the patient reported by Gershoni-Baruch et al. (1991).
The patients studied by Meira et al. (2000), the surviving boy of a dizygotic male-female twin pair and a girl who was not closely related, were related to the Manitoba aboriginal population group within which COFS syndrome was originally reported by Lowry et al. (1971) and Pena and Shokeir (1974). The twins had microcephaly, deep-set eyes, bilateral microphthalmia and cataracts, overhanging upper lips, and prominent noses, and the boy had undescended testes. They showed failure to thrive, recurrent pneumonias, axial hypotonia, appendicular hypertonia, hyperreflexia, and progressive contractures. Both were considered to have typical COFS syndrome. The girl died at age 5 years. Cranial computed tomography (CT) had shown enlargement of the ventricles and subarachnoid spaces, with calcifications in the periventricular frontal white matter and basal ganglia. Autopsy showed severe neurodegeneration, with markedly reduced brain weight, patchy demyelination in the cerebrum and hindbrain, neuronal loss and gliosis in the cerebral cortex, and pericapillary and parenchymal mineralization in the cortex and basal ganglia; this was case 7 in the study of Del Bigio et al. (1997). The boy showed normal hearing at age 2 years, but profound hearing loss by age 6 years, when he was found to have insulin resistance. At age 7 years he had CT changes similar to those in his sister. He never manifested cutaneous photosensitivity or actinic keratoses, but at age 10 years he had ocular photosensitivity with consistently constricted pupils. The boy died at age 11 years. In the third patient reported by Meira et al. (2000), the diagnosis of COFS syndrome was made at 2 years. The patient was the daughter of aboriginal parents from the same population as the dizygotic twins, although they were not known to be related. She presented at birth with growth deficiency, microcephaly, and bilateral microphthalmia with cataracts.
Jaakkola et al. (2010) reported a large multigenerational consanguineous Finnish kindred in which 6 individuals had COFS1. Two deceased patients had originally been reported by Linna et al. (1982) as having COFS, 1 of whom had intracranial calcifications. Two patients, a boy and a girl, were reported in detail. Clinical features included failure to thrive, poor growth, lack of psychomotor development with inability to sit independently or speak, and arthrogryposis. Facial dysmorphism included microcephaly, deep-set eyes, cataracts, prominent nasal bridge, micrognathia, large ear pinna, and upper lip overlapping the lower lip. Both also had hearing loss and nystagmus; 1 developed seizures. Brain MRI showed hypoplasia of the corpus callosum, ventriculomegaly, and delayed myelination. The boy had cryptorchidism. The other family members had a similar phenotype. All patients died between ages 3 and 9 years. Cultured fibroblasts from the 2 patients reported in detail showed 3.6- to 5.4-fold hypersensitivity to UV irradiation due to a defect in transcription-coupled nucleotide excision repair (TC-NER). Complementation analysis showed that the gene responsible was ERCC6.
Diagnosis
Laugel et al. (2008) proposed that diagnosis of COFS syndrome should require the following criteria: congenital microcephaly, congenital cataracts and/or microphthalmia, arthrogryposis, severe developmental delay, severe postnatal growth failure, and facial dysmorphism with prominent nasal root and/or overhanging upper lip, as well as a DNA repair defect in the transcription coupled repair pathway.
Cytogenetics
Temtamy et al. (1996) described a 3-year-old Egyptian girl, the only child of healthy first-cousin parents, with phenotypic abnormalities of the COFS syndrome. She had microcephaly, bilateral congenital cataract, nystagmus, long ear pinnae, camptodactyly, prominent heels, coxa valga, kyphosis, and flexure contracture of the elbows and knees. CT scan showed bilateral symmetric intracranial calcifications. In addition, she had an apparently balanced translocation: 46,XX,t(1;16)(q23;q13) in all cells. The translocation was transmitted from the phenotypically normal mother who was a mosaic for the translocation. Temtamy et al. (1996) suggested that a gene for COFS may be located on 1q23 or 16q13.
Molecular Genetics
Meira et al. (2000) presented evidence that 2 probands related to the Manitoba aboriginal population group within which COFS syndrome was originally reported by Lowry et al. (1971) and Pena and Shokeir (1974) had cellular phenotypes indistinguishable from those in Cockayne syndrome cells. Furthermore, the patients had an identical mutation in the ERCC6 gene (609413.0007).
In 3 unrelated patients with COFS syndrome, Laugel et al. (2008) identified biallelic mutations in the ERCC6 gene (see, e.g., 609413.0012-609413.0014). All patients showed classic clinical features of the disorder and cultured fibroblasts showed defective DNA repair.
In 3 of 6 patients with COFS1 from a consanguineous Finnish family, Jaakkola et al. (2010) identified a homozygous mutation in the ERCC6 gene (R1288X; 609413.0015). Fibroblast studies showed that the mutation caused a severe reduction of the encoded protein to 20% of controls. Genealogic analysis revealed that common ancestors for all the patients lived in the 18th century in a small village in northern Finland, consistent with a founder effect.
Nomenclature
Shokeir (1982) suggested that there are two types of Pena-Shokeir syndrome: type I (208150), which shows multiple ankyloses, camptodactyly, facial anomalies and pulmonary hypoplasia (Pena and Shokeir (1974, 1976)); and type II, also known as the COFS syndrome. In the third edition of Recognizable Patterns of Human Malformations, Smith (1982) also suggested that COFS be called Pena-Shokeir syndrome II. Because of potential confusion, this seems best avoided and the designation COFS used instead. Silengo et al. (1984) reported a newborn female with a phenotype intermediate between the Neu-Laxova (256520) and COFS syndromes. They espoused the notion, stated earlier by Preus and Fraser (1974) and by Temtamy and McKusick (1978), that these two separately named syndromes represent different degrees of clinical expressivity of the same autosomal recessive mutation.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Normal or decreased birth weight \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- Micrognathia \- Sloping forehead \- Long philtrum Ears \- Large ear pinnae \- Sensorineural hearing loss Eyes \- Cataracts \- Blepharophimosis \- Microphthalmia \- Deep-set eyes \- Nystagmus Nose \- Prominent nasal root Mouth \- Upper lip overlaps lower lip \- Thin lips CHEST Breasts \- Widely spaced nipples SKELETAL \- Arthrogryposis \- Osteoporosis Spine \- Kyphoscoliosis Pelvis \- Coxa valga \- Shallow acetabular angle Limbs \- Elbow flexion contracture \- Knee flexion contracture Hands \- Camptodactyly Feet \- Vertical talus \- Rocker-bottom feet \- Longitudinal groove on soles \- Second metatarsal posteriorly placed SKIN, NAILS, & HAIR Hair \- Hirsutism NEUROLOGIC Central Nervous System \- Mental retardation, profound \- Lack of motor development \- Lack of speech development \- Optic tract and chiasm hypoplasia \- Focal microgyria \- Agenesis of corpus callosum \- Infantile spasm \- Hypotonia \- Delayed myelination \- Cerebellar hypoplasia \- Subcortical gliosis \- Third ventricle subependymal focal gliosis LABORATORY ABNORMALITIES \- Fibroblasts show hypersensitivity to UV irradiation due to defect in transcription-coupled nucleotide excision repair (TC-NER) MISCELLANEOUS \- Death in childhood MOLECULAR BASIS \- Caused by mutation in the excision repair cross complementing rodent repair deficiency, complementation group 6 gene (ERCC6, 133540.0007 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CEREBROOCULOFACIOSKELETAL SYNDROME 1
|
c0009207
| 7,557 |
omim
|
https://www.omim.org/entry/214150
| 2019-09-22T16:29:49 |
{"mesh": ["D003057"], "omim": ["214150"], "orphanet": ["191", "1466"], "synonyms": ["Alternative titles", "COFS SYNDROME", "PENA-SHOKEIR SYNDROME, TYPE II"]}
|
Advanced stage of peripheral artery disease
Chronic limb threatening ischemia
Other namesCritical limb ischemia, limb threat
Chronic limb threatening ischemia (CLTI), also known as critical limb ischemia (CLI), is an advanced stage of peripheral artery disease (PAD). It is defined as ischemic rest pain, arterial insufficiency ulcers, and gangrene. The latter two conditions are jointly referred to as tissue loss, reflecting the development of surface damage to the limb tissue due to the most severe stage of ischemia. Compared to the other manifestation of PAD, intermittent claudication, CLI has a negative prognosis within a year after the initial diagnosis, with 1-year amputation rates of approximately 12% and mortality of 50% at 5 years and 70% at 10 years.[1]
CLI was conceived to identify patients at high-risk for major amputation, but the increasing prevalence of diabetes mellitus has led to a broader conception of limb threat that includes the risk of amputation associated with severely infected and non-healing wounds.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Rest pain
* 1.2 Tissue loss
* 2 Diagnosis
* 3 Treatment
* 4 Research
* 5 References
* 6 External links
## Signs and symptoms[edit]
Critical limb ischemia includes rest pain and tissue loss.
### Rest pain[edit]
Rest pain is a continuous burning pain of the lower leg or feet. It begins, or is aggravated, after reclining or elevating the limb and is relieved by sitting or standing. It is more severe than intermittent claudication, which is also a pain in the legs from arterial insufficiency.
### Tissue loss[edit]
Tissue loss is the development of arterial insufficiency ulcers or gangrene due to peripheral artery disease.
## Diagnosis[edit]
Critical limb ischemia is diagnosed by the presence of ischemic rest pain, and an ulcers that will not heal or gangrene due to insufficient blood flow.[3] Insufficient blood flow may be confirmed by ankle-brachial index (ABI), ankle pressure, toe-brachial index (TBI), toe systolic pressure, transcutaneous oxygen measurement (TcPo2 ), or skin perfusion pressure (SPP).[3]
Other factors which may point to a diagnosis of critical limb ischemia are a Buerger's angle of less than 20 degrees during Buerger's test, a capillary refill of more than 15 seconds or diminished or absent pulses.
Critical limb ischemia is different from acute limb ischemia. Acute limb ischemia is a sudden lack of blood flow to the limb, for example caused by an embolus whereas critical limb ischemia is a late sign of a progressive chronic disease.
## Treatment[edit]
Treatment mirrors that of other symptoms of peripheral artery disease, and includes modifying risk factors, revascularization via vascular bypass or angioplasty, and in the case of tissue loss, wound debridement.
## Research[edit]
As of 2015 pCMV-vegf165, a gene-therapy was being studied in critical limb ischemia.[4]
In 2014, a trial was started to better understand the best revascularization technique for CLI. As of 2017, it had enrolled nearly half of the 2100 people needed to complete the trial.[5] A similar study, BASIL 2 (Bypass Versus Angio plasty in Severe Ischaemia of the Leg), is being conducted in the United Kingdom.[6]
## References[edit]
1. ^ Varu, Vinit N; Hogg, Melissa E; Kibbe, Melina R (2010). "Critical limb ischemia". Journal of Vascular Surgery. 51 (1): 230–41. doi:10.1016/j.jvs.2009.08.073. PMID 20117502.
2. ^ Mills, Joseph L; Conte, Michael S; Armstrong, David G; Pomposelli, Frank B; Schanzer, Andres; Sidawy, Anton N; Andros, George; Society for Vascular Surgery Lower Extremity Guidelines Committee (2014). "The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI)". Journal of Vascular Surgery. 59 (1): 220–34.e1–2. doi:10.1016/j.jvs.2013.08.003. PMID 24126108.
3. ^ a b Misra, Sanjay; Shishehbor, Mehdi H.; Takahashi, Edwin A.; Aronow, Herbert D.; Brewster, Luke P.; Bunte, Matthew C.; Kim, Esther S.H.; Lindner, Jonathan R.; Rich, Kathleen (12 August 2019). "Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association". Circulation. 140 (12): e657–e672. doi:10.1161/CIR.0000000000000708. PMC 7372288. PMID 31401843.
4. ^ Deev, Roman V; Bozo, Ilia Y; Mzhavanadze, Nina D; Voronov, Dmitriy A; Gavrilenko, Aleksandr V; Chervyakov, Yuriy V; Staroverov, Ilia N; Kalinin, Roman E; Shvalb, Pavel G; Isaev, Artur A (2015). "PCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients with Chronic Lower Limb Ischemia". Journal of Cardiovascular Pharmacology and Therapeutics. 20 (5): 473–82. doi:10.1177/1074248415574336. PMID 25770117. S2CID 13443907.
5. ^ Menard, Matthew T; Farber, Alik; Assmann, Susan F; Choudhry, Niteesh K; Conte, Michael S; Creager, Mark A; Dake, Michael D; Jaff, Michael R; Kaufman, John A; Powell, Richard J; Reid, Diane M; Siami, Flora Sandra; Sopko, George; White, Christopher J; Rosenfield, Kenneth (2016). "Design and Rationale of the Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST‐CLI) Trial". Journal of the American Heart Association. 5 (7): e003219. doi:10.1161/JAHA.116.003219. PMC 5015366. PMID 27402237.
6. ^ Popplewell, Matthew A; Davies, Huw; Jarrett, Hugh; Bate, Gareth; Grant, Margaret; Patel, Smitaa; Mehta, Samir; Andronis, Lazaros; Roberts, Tracy; Deeks, Jon; Bradbury, Andrew (2016). "Bypass versus angio plasty in severe ischaemia of the leg - 2 (BASIL-2) trial: Study protocol for a randomised controlled trial". Trials. 17: 11. doi:10.1186/s13063-015-1114-2. PMC 4704263. PMID 26739146.
## External links[edit]
* Cochrane Peripheral Vascular Diseases Review Group
* 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
|
Chronic limb threatening ischemia
|
c1142264
| 7,558 |
wikipedia
|
https://en.wikipedia.org/wiki/Chronic_limb_threatening_ischemia
| 2021-01-18T18:57:03 |
{"umls": ["C1142264"], "wikidata": ["Q7316059"]}
|
Spinocerebellar ataxia type 21 (SCA21) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar ataxia, mild cognitive impairment, postural and/or resting tremor, bradykinesia, and rigidity.
## Epidemiology
Prevalence is unknown. Fewer than 20 cases in a 4-generation French family have been reported to date.
## Clinical description
Mean age of onset is 17.4 years and is relatively early compared to most type I ADCAs. Individuals in successive generations tend to have earlier ages of onset. Parkinsonism was not responsive to L-dopa and magnetic resonance imaging (MRI) revealed cerebellar and brainstem atrophy.
## Etiology
SCA21 maps to chromosome 7p21.3-p15.1 but the gene and gene mutation have not been identified.
## Prognosis
There is insufficient clinical data to draw conclusions concerning prognosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spinocerebellar ataxia type 21
|
c1843891
| 7,559 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98773
| 2021-01-23T17:31:28 |
{"gard": ["9999"], "mesh": ["C537200"], "omim": ["607454"], "umls": ["C1843891"], "icd-10": ["G11.1"], "synonyms": ["SCA21"]}
|
Mental retardation-hypotonic facies covers a group of X-linked syndromes characterized by severe intellectual deficit and facial dysmorphism, with variable other features.
## Epidemiology
Prevalence is unknown but most of these syndromes have been reported in only a few families.
## Clinical description
At present this group includes the Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, Renier-Gabreels-Jasper, Smith-Fineman-Myers and Chudley-Lowry syndromes (see these terms).
## Etiology
These syndromes are caused by a mutation in the helicase 2 (XH2/ATRX; Xq13.3) gene.
## Differential diagnosis
These syndromes show clinical similarity to alpha-thalassemia-X-linked mental retardation (ATR-X syndrome; see this term), which is also caused by a mutation in the ATRX gene, but all patients with a mental retardation-hypotonic facies syndrome display normal haematologic indices and do not appear to exhibit the haemoglobin H inclusions characteristic of ATR-X.
## Genetic counseling
Transmission is X-linked recessive. A highly skewed X-inactivation pattern was identified in female carriers and some of the heterozygous mothers were reported to have manifestations such as subnormal intelligence and microcephaly.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked intellectual disability-hypotonic face syndrome
|
c0796003
| 7,560 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=73220
| 2021-01-23T19:11:41 |
{"mesh": ["C537457"], "omim": ["309580"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of schizophrenia, see (181500).
Mapping
Fallin et al. (2003) performed a genomewide linkage scan for schizophrenia (181500) susceptibility regions in 29 multiplex families of Ashkenazi Jewish descent. Although there is no evidence that the rate of schizophrenia among the Ashkenazim differs from that in other populations, they focused on this population in hopes of reducing genetic heterogeneity among families and increasing the detectable effects of any particular locus. They achieved the strongest signal at chromosome 10q22.3 (D10S1686), with a nonparametric linkage score (NPL) of 3.35 (genomewide empirical P = 0.035) and a dominant heterogeneity lod score (hlod) of 3.14. Upon follow-up with an additional 23 markers in the chromosome 10q region, the peak NPL score increased to 4.27 (D10S1774; empirical P = 0.00002), with a 95% confidence interval of 12.2 Mb for the location of the trait locus (D10S1677 to D10S1753).
By SNP analysis of a large Ashkenazi Jewish population, Chen et al. (2009) were unable to find an association between the binary presence or absence of schizophrenia and multiple SNPs spanning the 10q candidate region. However, using the 'delusion' factor as an endophenotype, the authors found significant association with SNP rs10883866 (p = 7.26 x 10(-7) after Bonferroni correction) in intron 1 of the NRG3 gene (605533) in a group of 285 parent-child trios. The findings were replicated in a second group of 173 patients (p = 1.55 x 10(-2)), yielding a combined p value of 2.30 x 10(-7). Weaker association signals were found for other SNPs in the NRG3 gene.
Kao et al. (2010) replicated the findings of Chen et al. (2009) of an association between schizophrenia and SNPs in the NRG3 gene, and confirmed the specific association with delusions and positive symptoms. However, Kao et al. (2010) found that the common T allele of rs10748842 and the common G allele of rs6584400 were associated with the disorder, which was the opposite allelic association reported by Chen et al. (2009). This discrepancy was explained by population differences, multilocus interactions and epistasis, environmental factors, or linkage disequilibrium. The study by Kao et al. (2010) included 356 families with an offspring with schizophrenia and another group of 445 affected probands. Significant associations were found with SNPs in intron 1 of NRG3, including the 13-kb interval with rs10883866, rs10748842, and rs6584400 previously reported by Chen et al. (2009) and with rs10399981, an additional SNP residing in the 13-kb interval. The most significant association found by Kao et al. (2010) spanned an 80-kb interval of intron 1, with the most significant SNPs being rs1336286 and rs1649960. The common T allele of rs10748842 is located within a binding site for multiple transcription factors and is associated with increased expression of NRG3. Kao et al. (2010) also observed differential expression of various NRG3 transcripts in brain tissue of patients with schizophrenia compared to controls, and suggested that differential regulation of NRG3 isoforms may affect neurodevelopmental pathways and play a role in the development of schizophrenia.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SCHIZOPHRENIA 11
|
c1842605
| 7,561 |
omim
|
https://www.omim.org/entry/608078
| 2019-09-22T16:08:20 |
{"omim": ["608078"], "synonyms": ["Alternative titles", "SCZD11", "SCHIZOPHRENIA SUSCEPTIBILITY LOCUS, CHROMOSOME 10q-RELATED"]}
|
Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified (also termed: EBV positive diffuse large B cell lymphoma, NOS; EBV+ DLBCL, NOS; or EBV+ DLBCL) was initially termed in the WHO 2008 classification as Epstein–Barr virus -positive DLBCL of the elderly because it was a specific type of large B-cell lymphoma that appeared to be limited to elderly (e.g. >50 years old) individuals.[1][2]:369–370[3] Since this 2008 WHO classification, however, the disorder has been diagnosed in much younger adults and children.[4] Accordingly, the WHO classification of 2016 renamed this order as EBV+ DLBCL, NOS.[5] The disease is also classified as one of numerous related and interrelated Epstein-Barr virus-associated lymphoproliferative diseases.[4]
EBV+ DLBCL, NOS is usually CD20 positive, and has clonal immunoglobulin gene rearrangement.[2]:380
## Biology[edit]
This section needs expansion. You can help by adding to it. (March 2015)
This type of lymphoma is not associated with immunodeficiency.[2]:369 Although reported almost exclusively in Asians, it is not confined to that population.[2]:369[6] The disease usually has an extranodal presentation, with or without lymph node involvement.[2]:369
Morphologically, areas of necrosis are often seen[2]:370[3] as well as Reed–Sternberg-like cells.[2]:370[3] There are two subtypes: one with monotonous large cells, the other with numerous cell sizes as well as reactive cells, but different clinical behavior is not appreciated between these subtypes.[2]:370 Morphological differential diagnosis is Hodgkin lymphoma.[2]:370
Median survival 2 years, 25% 5-year survival.[2]:369
## See also[edit]
* Lymphoma
## References[edit]
1. ^ Swerdlow, Steven H.; International Agency for Research on Cancer; World Health Organization (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. 2 (4th ed.). International Agency for Research on Cancer. ISBN 9789283224310.
2. ^ a b c d e f g h i j Jaffe ES, Harris NL, Vardiman JW, Campo E, Arber, DA (2011). Hematopathology (1st ed.). Elsevier Saunders. ISBN 9780721600406.
3. ^ a b c Adam P, Bonzheim I, Fend F, Quintanilla-Martínez L (2011). "Epstein-Barr virus-positive diffuse large B-cell lymphomas of the elderly". Adv Anat Pathol. 18 (5): 349–55. doi:10.1097/PAP.0b013e318229bf08. PMID 21841405.
4. ^ a b Dojcinov SD, Fend F, Quintanilla-Martinez L (March 2018). "EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts". Pathogens (Basel, Switzerland). 7 (1). doi:10.3390/pathogens7010028. PMC 5874754. PMID 29518976.
5. ^ 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.
6. ^ Ok CY, Papathomas TG, Medeiros LJ, Young KH (2013). "EBV-positive diffuse large B-cell lymphoma of the elderly". Blood. 122 (3): 328–40. doi:10.1182/blood-2013-03-489708. PMC 3779382. PMID 23649469.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Epstein Barr virus positive diffuse large B-cell lymphoma, not otherwise specified
|
c2700007
| 7,562 |
wikipedia
|
https://en.wikipedia.org/wiki/Epstein_Barr_virus_positive_diffuse_large_B-cell_lymphoma,_not_otherwise_specified
| 2021-01-18T19:04:10 |
{"umls": ["C2700007"], "orphanet": ["289661"], "wikidata": ["Q25112638"]}
|
For the term formerly used in reference to compulsive drinking of alcohol, see Dipsomania.
Primary polydipsia
Other namesPsychogenic polydipsia, compulsive drinking, psychosis-intermittent hyponatremia-polydipsia (PIP) syndrome
Patients with PPD often prefer ice cold water
SpecialtyPsychiatry
SymptomsXerostomia, polydipsia, fluid-seeking behavior
ComplicationsWater intoxication
Primary polydipsia, or psychogenic polydipsia, is a form of polydipsia[1] characterised by excessive fluid intake in the absence of physiological stimuli to drink.[2] Psychogenic polydipsia which is caused by psychiatric disorders, often schizophrenia, is often accompanied by the sensation of dry mouth. Some forms of polydipsia are explicitly non-psychogenic. Primary polydipsia is a diagnosis of exclusion.
## Contents
* 1 Signs and symptoms
* 2 Brain differences
* 3 Diagnosis
* 3.1 Patient profiles
* 4 Treatment
* 4.1 Acute hyponatraemia
* 4.2 Fluid restriction
* 4.3 Behavioural
* 4.4 Pharmaceutical
* 5 Terminology
* 6 Non-psychogenic
* 7 Non-human animals
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
Signs and symptoms of psychogenic polydipsia include:[3]
* Excessive thirst and xerostomia, leading to overconsumption of water
* Hyponatraemia, causing headache, muscular weakness, twitching, confusion, vomiting, irritability etc., although this is only seen in 20% – 30% of cases.[4]
* Hypervolemia, leading to oedema, hypertension and weight gain (due to the kidneys being unable to filter the excess blood)[5] in extreme episodes
* Tonic-clonic seizure[6]
* Behavioural changes, including fluid-seeking behaviour; patients have been known to seek fluids from any available source, such as toilets and shower rooms.[5][7]
The most common presenting symptom is tonic-clonic seizure, found in 80% of patients.[8] Psychogenic polydipsia should be considered a life-threatening condition, since it has been known to cause severe hyponatraemia, leading to cardiac arrest, coma and cerebral oedema.[3] It can also cause central pontine myelinolysis.
## Brain differences[edit]
Location of the insular cortex, a structure implicated in PPD
Psychogenic polydipsia individuals with schizophrenia is associated with differences seen in neuroimaging. MRI scans may be used to help with differentiating between PPD and diabetes insipidus, such as by examining the signal of the posterior pituitary (weakened or absent in central DI).[9] Some patients, most often with a history of mental illness, show a shrunken cortex and enlarged ventricles on an MRI scan, which makes differentiation between psychogenic and physiological cause difficult.[5] However, these changes will likely only develop after chronic PPD associated with severe mental illness, as opposed to less severe forms of the disorder as seen in those with anxiety and affective disorders. PPD is also linked with significant reductions in insular cortex volume,[10] although this may be caused by the secondary hyponatraemia. It has been suggested that these deficits lead to moderate to severe cognitive impairments, especially affecting working memory, verbal memory, executive function, attention and motor speed.[11]
Other areas with volume reductions (both white and grey matter) include:[10][11]
* Right posterior lobe
* Right inferior temporal gyrus
* Parahippocampal gyrus
* Both left and right superior temporal gyri
* Right cuneus
* Left medial frontal gyryus and inferior frontal gyrus
* Right lingual gyrus
## Diagnosis[edit]
As a diagnosis of exclusion, a diagnosis of primary polydipsia may be the result of elimination of the possibility of diseases causing similar signs and symptoms, such as diabetes insipidus.[12] Diagnosis may be complicated by the fact that chronic and extreme compulsive drinking may impair the response of the kidneys to vasopressin, thus reducing the kidney's ability to concentrate the urine.[13] This means that psychogenic polydipsia may lead to test results (e.g. in a water restriction test) consistent with diabetes insipidus or SIADH, leading to misdiagnosis.[14]
Dry mouth is often a side effect of medications used in the treatment of some mental disorders, rather than being caused by the underlying condition.[15] Such medications include antipsychotics, antidepressants, anticonvulsants, alpha agonists and anticholinergics.[16] It should also be ensured that the thirst isn't caused by diuretic use (particularly thiazide diuretics), MDMA use, excessive solute intake or chronic alcoholism. Alcoholism may cause physiological thirst since ethanol inhibits vasopressin, the hormone primarily responsible for water retention in osmoregulation.[17][18][19] The following conditions should also be excluded: DI, cerebral salt wasting, pseudohyponatraemia caused by hyperlipidemia or hyperparaproteinemia, SIADH, mineralcorticoid deficiency, salt-wasting nephropathy, nephrotic syndrome, chronic heart failure and cirrhosis.[20]
Tobacco smoking is an often overlooked factor linked to hyponatremia, due to the ADH-releasing effect of nicotine, although this is usually limited to heavy smokers.[21] One study suggested that around 70% of patients with self-induced polydipsia were tobacco smokers.[22] Diagnostic tests for primary polydipsia usually involves the fluid deprivation test to exclude ADH problems. The desmopressin test is also used, in which the synthetic hormone is used as a diagnostic workup to test for inappropriate secretion of vasopressin, as seen in DI and SIADH.
### Patient profiles[edit]
Psychogenic polydipsia is found in patients with mental illnesses, most commonly schizophrenia, but also anxiety disorders and rarely affective disorders, anorexia nervosa and personality disorders. PPD occurs in between 6% and 20% of psychiatric inpatients.[23] It may also be found in people with developmental disorders, such as those with autism.[24] While psychogenic polydipsia is usually not seen outside the population of those with serious mental disorders, it may occasionally be found among others in the absence of psychosis, although there is no existent research to document this other than anecdotal observations. Such persons typically prefer to possess bottled water that is ice-cold, consume water and other fluids at excessive levels.[medical citation needed] However, a preference for ice-cold water is also seen in diabetes insipidus.[25][26]
## Treatment[edit]
Estimation of serum sodium levels from weight gain and suggested interventions[27] Weight gained (% body mass) Estimated serum sodium (mmol/L) Suggested intervention
0-3 140 - 134 No direct intervention, monitoring
3-5 133 - 130 Redirection from water sources
5-7 129–126 Oral NaCl and redirection
7–10 125–120 Oral NaCl and redirection, possibly restraint
> 10 < 120 Slow IV saline, seizure precautions
Treatment for psychogenic polydipsia depends on severity and may involve behavioural and pharmacological modalities.[28]
### Acute hyponatraemia[edit]
If the patient presents with acute hyponatraemia (overhydration) caused by psychogenic polydipsia, treatment usually involves administration of intravenous hypertonic (3%) saline until the serum sodium levels stabilise to within a normal range, even if the patient becomes asymptomatic.[29]
### Fluid restriction[edit]
If the patient is institutionalised, monitoring of behaviour and serum sodium levels is necessary. In treatment-resistant polydipsic psychiatric patients, regulation in the inpatient setting can be accomplished by use of a weight-water protocol.[30] First, base-line weights must be established and correlated to serum sodium levels. Weight will normally fluctuate during the day, but as the water intake of the polydipsic goes up, the weight will naturally rise. The physician can order a stepped series of interventions as the weight rises. The correlation must be individualized with attention paid to the patient's normal weight and fluctuations, diet, comorbid disorders (such as a seizure disorder) and urinary system functioning. Progressive steps might include redirection, room restriction, and increasing levels of physical restraint with monitoring. Such plans should also include progressive increases in monitoring, as well as a level at which a serum sodium level is drawn.
### Behavioural[edit]
Behavioural treatments may involve the use of a token economy to provide positive reinforcement to desirable behaviour.[28] Furthermore, cognitive therapy techniques can be used to address the thought patterns that lead to compulsive drinking behaviour. Success has been seen in trials of this technique, with emphasis on the development of coping techniques (e.g. taking small sips of water, having ice cubes instead of drinks) in addition to challenging delusions leading to excessive drinking.[31][better source needed]
Psychogenic polydipsia often leads to institutionalisation of mentally ill patients, since it is difficult to manage in the community.[5] Most studies of behavioural treatments occur in institutional settings and require close monitoring of the patient and a large degree of time commitment from staff.[29]
### Pharmaceutical[edit]
Risperdal (risperidone) tablets
A number of pharmaceuticals may be used in an attempt to bring the polydipsia under control, including:
* Atypical antipsychotics, such as clozapine,[32] olanzapine and risperidone[33]
* Demeclocycline, a tetracycline antibiotic, which is effective due to the side effect of inducing nephrogenic diabetes insipidus.[29][34] Demeclocycline is used for cases of psychogenic polydipsia, including those with nocturnal enuresis (bed-wetting). Its mechanism of action involves direct inhibition of vasopressin at the DCTs, thus reducing urine concentration.[29]
There are a number of emerging pharmaceutical treatments for psychogenic polydipsia, although these need further investigation:[35]
* ACE Inhibitors, such as enalapril[36]
* Clonidine, an alpha-2 adrenergic agonist[36]
* Irbesartan, an angiotensin II receptor antagonist[33]
* Propranolol, a sympatholytic beta blocker[37]
* Vasopressin receptor antagonists, such as conivaptan[38]
* Acetazolamide, a carbonic anhydrase inhibitor[39]
Lithium was previously used for treatment of PPD as a direct competitive ADH agonist, but is now generally avoided due to its toxic effects on the thyroid and kidneys.[29]
It is important to note that the majority of psychotropic drugs (and a good many of other classes) can cause dry mouth as a side effect, but this is not to be confused with true polydipsia in which a dangerous drop in serum sodium will be seen.[40]
## Terminology[edit]
In diagnosis, primary polydipsia is usually categorised as:
* Psychogenic (PPD) – caused by underlying psychiatric symptoms, including those caused by psychoses and rarely by affective disorders
* Non-psychogenic – another non-psychological cause, including idiopathic (unknown cause)
The terms primary polydipsia and psychogenic polydipsia are sometimes incorrectly used interchangeably – to be considered psychogenic, the patient needs to have some other psychiatric symptoms, such as delusions involving fluid intake or other unusual behaviours. Primary polydipsia may have physiological causes, such as autoimmune hepatitis.
Since primary polydipsia is a diagnosis of exclusion, the diagnosis may be made for patients who have medically unexplained excessive thirst, and this is sometimes incorrectly referred to as psychogenic rather than primary polydipsia.[13]
## Non-psychogenic[edit]
Although primary polydipsia is usually categorised as psychogenic, there are some rare non-psychogenic causes. An example is polydipsia found in patients with autoimmune chronic hepatitis with severely elevated globulin levels.[41] Evidence for the thirst being non-psychogenic is gained from the fact that it disappears after treatment of the underlying disease.
## Non-human animals[edit]
Psychogenic polydipsia is also observed in some non-human patients, such as in rats and cats.[42]
## See also[edit]
* Water intoxication
* Fluid deprivation test
## References[edit]
1. ^ Saito T, Ishikawa S, Ito T, et al. (June 1999). "Urinary excretion of aquaporin-2 water channel differentiates psychogenic polydipsia from central diabetes insipidus". Journal of Clinical Endocrinology and Metabolism. 84 (6): 2235–2237. doi:10.1210/jc.84.6.2235. PMID 10372737.
2. ^ "Psychogenic polydipsia - Symptoms, diagnosis and treatment | BMJ Best Practice". bestpractice.bmj.com. Retrieved 29 December 2019.
3. ^ a b Gill, Melissa; McCauley, MacDara (2015-01-21). "Psychogenic Polydipsia: The Result, or Cause of, Deteriorating Psychotic Symptoms? A Case Report of the Consequences of Water Intoxication". Case Reports in Psychiatry. 2015: 846459. doi:10.1155/2015/846459. ISSN 2090-682X. PMC 4320790. PMID 25688318.
4. ^ de Leon, Jose; Verghese, Cherian; Tracy, Joseph I.; Josiassen, Richard C.; Simpson, George M. (1994). "Polydipsia and water intoxication in psychiatric patients: A review of the epidemiological literature". Biological Psychiatry. 35 (6): 408–419. doi:10.1016/0006-3223(94)90008-6. PMID 8018788.
5. ^ a b c d Hutcheon, Donald. "Psychogenic Polydipsia (Excessive Fluid seeking Behaviour)" (PDF). American Psychological Society Divisions. Retrieved 29 October 2016.
6. ^ Hedges, D.; Jeppson, K.; Whitehead, P. (2003). "Antipsychotic medication and seizures: A review". Drugs of Today. 39 (7): 551–557. doi:10.1358/dot.2003.39.7.799445. PMID 12973403.
7. ^ Perch, Julia; O’Connor, Kevin M. "Insatiable thirst: Managing polydipsia". Current Psychiatry. 8 (7): 82.
8. ^ Ferrier, I N (1985-12-07). "Water intoxication in patients with psychiatric illness". British Medical Journal (Clinical Research Ed.). 291 (6509): 1594–1596. doi:10.1136/bmj.291.6509.1594. ISSN 0267-0623. PMC 1418423. PMID 3935199.
9. ^ Moses, A. M.; Clayton, B.; Hochhauser, L. (1992-09-01). "Use of T1-weighted MR imaging to differentiate between primary polydipsia and central diabetes insipidus". American Journal of Neuroradiology. 13 (5): 1273–1277. ISSN 0195-6108. PMID 1414815.
10. ^ a b Nagashima, Tomohisa; Inoue, Makoto; Kitamura, Soichiro; Kiuchi, Kuniaki; Kosaka, Jun; Okada, Koji; Kishimoto, Naoko; Taoka, Toshiaki; Kichikawa, Kimihiko (2012-01-01). "Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia". BMC Psychiatry. 12: 210. doi:10.1186/1471-244X-12-210. ISSN 1471-244X. PMC 3532364. PMID 23181904.
11. ^ a b "Polydipsia linked to brain alterations in schizophrenia". News-Medical.net. 2012-11-28. Retrieved 2016-12-08.
12. ^ "Psychogenic polydipsia – Diagnosis – Approach". British Medical Journal. 5 May 2016. Retrieved 29 October 2016.
13. ^ a b "Primary polydipsia – General Practice Notebook". GPnotebook. Retrieved 29 October 2016.
14. ^ Zerbe, R. L.; Robertson, G. L. (1981-12-24). "A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria". The New England Journal of Medicine. 305 (26): 1539–1546. doi:10.1056/NEJM198112243052601. ISSN 0028-4793. PMID 7311993.
15. ^ Rippe, James M.; Irwin, Richard S. (2008). Irwin and Rippe's Intensive care medicine. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 909. ISBN 978-0-7817-9153-3.
16. ^ "Psychotropic-induced dry mouth: Don't overlook this potentially serious side effect". Current Psychiatry. 10 (12): 54–58. December 2011.
17. ^ Swift, R.; Davidson, D. (1998-01-01). "Alcohol hangover: mechanisms and mediators". Alcohol Health and Research World. 22 (1): 54–60. ISSN 0090-838X. PMC 6761819. PMID 15706734.
18. ^ Taivainen, H.; Laitinen, K.; Tähtelä, R.; Kilanmaa, K.; Välimäki, M. J. (1995-06-01). "Role of plasma vasopressin in changes of water balance accompanying acute alcohol intoxication". Alcoholism, Clinical and Experimental Research. 19 (3): 759–762. doi:10.1111/j.1530-0277.1995.tb01579.x. ISSN 0145-6008. PMID 7573805.
19. ^ Fichman, M. P.; Kleeman, C. R.; Bethune, J. E. (1970-01-01). "Inhibition of Antidiuretic Hormone Secretion by Diphenylhydantoin". Archives of Neurology. 22 (1): 45–53. doi:10.1001/archneur.1970.00480190049008. ISSN 0003-9942. PMID 5409600.
20. ^ "Psychogenic polydipsia – Diagnosis – Differential diagnosis". British Medical Journal. 5 May 2016. Retrieved 29 October 2016.
21. ^ Blum, Alexander (1984-11-23). "The Possible Role of Tobacco Cigarette Smoking in Hyponatremia of Long-term Psychiatric Patients". JAMA: The Journal of the American Medical Association. 252 (20): 2864. doi:10.1001/jama.1984.03350200050022. ISSN 0098-7484.
22. ^ Jose, C. J.; Evenson, R. C. (1980-08-01). "Antecedents of self-induced water intoxication. A preliminary report". The Journal of Nervous and Mental Disease. 168 (8): 498–500. doi:10.1097/00005053-198008000-00009. ISSN 0022-3018. PMID 7400803.
23. ^ de Leon, Jose (2003-02-01). "Polydipsia—a study in a long-term psychiatric unit". European Archives of Psychiatry and Clinical Neuroscience. 253 (1): 37–39. doi:10.1007/s00406-003-0403-z. ISSN 0940-1334. PMID 12664312.
24. ^ "Psychogenic polydipsia – Theory – Aetiology". British Medical Journal. 5 May 2016. Retrieved 29 October 2016.
25. ^ Mayo Clinic internal medicine board review. Ghosh, Amit., Mayo Foundation for Medical Education and Research., Mayo Clinic. (9th ed.). [Rochester, MN.]: Mayo Clinic Scientific Press. 2010. p. 192. ISBN 9780199755691. OCLC 646395464.CS1 maint: others (link)
26. ^ Assessment (Lippincott Manual Handbook). Springhouse Publishing Co. 2006. p. 189. ISBN 978-1582559391.
27. ^ Leadbetter, Shutty Jr., Higgins, Pavalonis, Robert, Michael, Patricia, Diane (1994). "Multidisciplinary Approach to Psychosis, Intermittent Hyponatremia, and Polydipsia" (PDF). Schizophrenia Bulletin. 20 (2): 375–385. doi:10.1093/schbul/20.2.375. PMID 8085139.CS1 maint: multiple names: authors list (link)
28. ^ a b Dundas, Brian; Harris, Melissa; Narasimhan, Meera (2007-07-03). "Psychogenic polydipsia review: Etiology, differential, and treatment". Current Psychiatry Reports. 9 (3): 236–241. doi:10.1007/s11920-007-0025-7. ISSN 1523-3812. PMID 17521521.
29. ^ a b c d e "Psychogenic polydipsia – Management – Step by step". British Medical Journal. 5 May 2016. Retrieved 29 October 2016.
30. ^ Bowen, L.; Glynn, S. M.; Marshall, B. D.; Kurth, C. L.; Hayden, J. L. (1990-03-01). "Successful behavioral treatment of polydipsia in a schizophrenic patient". Journal of Behavior Therapy and Experimental Psychiatry. 21 (1): 53–61. doi:10.1016/0005-7916(90)90049-q. ISSN 0005-7916. PMID 2373769.(subscription required)
31. ^ Costanzo, Erin S.; Antes, Lisa M.; Christensen, Alan J. (2016-11-01). "Behavioral and medical treatment of chronic polydipsia in a patient with schizophrenia and diabetes insipidus". Psychosomatic Medicine. 66 (2): 283–286. doi:10.1097/01.psy.0000116717.42624.68. ISSN 1534-7796. PMID 15039516.(subscription required)
32. ^ Lee, H. S.; Kwon, K. Y.; Alphs, L. D.; Meltzer, H. Y. (1991-06-01). "Effect of clozapine on psychogenic polydipsia in chronic schizophrenia". Journal of Clinical Psychopharmacology. 11 (3): 222–223. doi:10.1097/00004714-199106000-00022. ISSN 0271-0749. PMID 2066464.
33. ^ a b Kruse, D.; Pantelis, C.; Rudd, R.; Quek, J.; Herbert, P.; McKinley, M. (2001-02-01). "Treatment of psychogenic polydipsia: comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan)". The Australian and New Zealand Journal of Psychiatry. 35 (1): 65–68. doi:10.1046/j.1440-1614.2001.00847.x. ISSN 0004-8674. PMID 11270459.(subscription required)
34. ^ Goh, Kian Peng (2004-05-15). "Management of Hyponatremia – American Family Physician". American Family Physician. 69 (10): 2387–2394. Retrieved 2016-10-29.
35. ^ "Psychogenic polydipsia – Management – Emerging treatments". British Medical Journal. 5 May 2016. Retrieved 29 October 2016.
36. ^ a b Greendyke, Robert M.; Bernhardt, Alan J.; Tasbas, Hedy E.; Lewandowski, Kathleen S. (1998-04-01). "Polydipsia in Chronic Psychiatric Patients: Therapeutic Trials of Clonidine and Enalapril". Neuropsychopharmacology. 18 (4): 272–281. doi:10.1016/S0893-133X(97)00159-0. ISSN 0893-133X. PMID 9509495.
37. ^ Shevitz, S. A.; Jameison, R. C.; Petrie, W. M.; Crook, J. E. (1980-04-01). "Compulsive water drinking treated with high dose propranolol". The Journal of Nervous and Mental Disease. 168 (4): 246–248. doi:10.1097/00005053-198004000-00011. ISSN 0022-3018. PMID 7365485.
38. ^ Douglas, Ivor (2006-09-01). "Hyponatremia: why it matters, how it presents, how we can manage it". Cleveland Clinic Journal of Medicine. 73 Suppl 3: S4–12. doi:10.3949/ccjm.73.suppl_3.s4. ISSN 0891-1150. PMID 16970147.
39. ^ Takagi, Shunsuke; Watanabe, Yutaka; Imaoka, Takefumi; Sakata, Masuhiro; Watanabe, Masako (2017-02-01). "Treatment of psychogenic polydipsia with acetazolamide: a report of 5 cases". Clinical Neuropharmacology. 34 (1): 5–7. doi:10.1097/WNF.0b013e318205070b. ISSN 1537-162X. PMID 21242740.(subscription required)
40. ^ Meulendijks, Didier; Mannesse, Cyndie K.; Jansen, Paul A. F.; van Marum, Rob J.; Egberts, Toine C. G. (2010-02-01). "Antipsychotic-induced hyponatraemia: a systematic review of the published evidence". Drug Safety. 33 (2): 101–114. doi:10.2165/11319070-000000000-00000. ISSN 1179-1942. PMID 20082537.(subscription required)
41. ^ Tobin MV, Morris AI (April 1988). "Non-psychogenic primary polydipsia in autoimmune chronic active hepatitis with severe hyperglobulinaemia". Gut. 29 (4): 548–9. doi:10.1136/gut.29.4.548. PMC 1433532. PMID 3371724.
42. ^ Falk, John L. (1969-05-01). "Conditions Producing Psychogenic Polydipsia in Animals*". Annals of the New York Academy of Sciences. 157 (2): 569–593. Bibcode:1969NYASA.157..569F. doi:10.1111/j.1749-6632.1969.tb12908.x. ISSN 1749-6632. PMID 5255630.
## Further reading[edit]
* Siegler EL, Tamres D, Berlin JA, Allen-Taylor L, Strom BL (May 1995). "Risk factors for the development of hyponatremia in psychiatric inpatients". Archives of Internal Medicine. 155 (9): 953–957. doi:10.1001/archinte.1995.00430090099011. PMID 7726704.
* Mauri MC, Volonteri LS, Fiorentini A, Dieci M, Righini A, Vita A (July 2002). "Efficacy of clozapine in a non-schizophrenic patient with psychogenic polydipsia and central pontine myelinolysis". Human Psychopharmacology. 17 (5): 253–255. doi:10.1002/hup.407. PMID 12404683.
## External links[edit]
* Psychogenic Polydipsia (Excessive Fluid seeking Behaviour) by Donald "Don" Hutcheon on the APA's website
Classification
D
* ICD-10: R63.1
* ICD-9-CM: 783.5
* MeSH: D059607
* DiseasesDB: 10318
External resources
* MedlinePlus: 003085
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary polydipsia
|
c0395005
| 7,563 |
wikipedia
|
https://en.wikipedia.org/wiki/Primary_polydipsia
| 2021-01-18T18:48:17 |
{"mesh": ["D059607"], "wikidata": ["Q929963"]}
|
## Clinical Features
Al Gazali et al. (1996) reported a female infant, born of double first cousins of Pakistani origin, with large head, wide anterior fontanel, corneal clouding, atretic auditory canals, severe shortness of limbs, especially of the distal segments, and bilateral clubfoot. Skeletal survey showed sclerotic bones, occipital synchondrosis, multiple wormian bones, platyspondyly, mesomelic shortening of the limbs, and shortening of all phalanges and metacarpals, especially the first metacarpal. The infant died a few minutes after birth. Al Gazali et al. (1996) could find no analogous cases in the literature. They suggested that this case represented a 'new' autosomal recessive form of skeletal dysplasia.
Grigelioniene et al. (2011) described 2 unrelated patients with al Gazali-type lethal skeletal dysplasia. The first was a female infant, born to nonconsanguineous Swedish parents, who died at 20 minutes of age due to respiratory failure. The mother's reproductive history included 1 spontaneous abortion, 1 healthy boy, and 1 intrauterine fetal death. Clinical examination showed an abnormally stiff body with short stature and a relatively big skull, with wide anterior fontanel, brachycephaly, hypertelorism, short neck, low-set ears with narrow auditory meatus, disproportionately short extremities with small hands and feet, severe brachydactyly and bilateral transverse creases of the palms, hirsutism, hypoplastic thorax, relatively large abdomen, bilateral abducted hips, and bilateral rigid clubfeet with small toes. Facial features were distorted by edema, but showed a flat face and small flat nose. Autopsy findings also showed hypoplastic frontal bones, broad occiput, and widened and abnormally shaped major fontanel. Thorax and lungs were hypoplastic, and there was severe hydrops. No structural abnormalities of the internal organs were evident. The second patient was a female infant who was stillborn to nonconsanguineous Japanese parents at 26 weeks' gestation. Clinical examination showed short stature with disproportionately short extremities and brachydactyly with ulnar deviation of fingers 2, 3, and 4, flat face with a small flat nose, hypertelorism, low-set deformed ears, and hirsutism. Pathologic examination revealed fetal hydrops, pulmonary stenosis, branching anomaly of the subclavian artery, and calcification of the left heart endocardium. Skeletal survey was similar in both patients, and showed generally sclerotic bones, with short and poorly modeled long tubular bones that had wide diaphyses and smooth, rounded metaphyses. Cortical bones as well as vertebral endplates were thickened. The skull was sclerotic and brachycephalic with prominent parietal bones and a large anterior fontanel. The thorax was hypoplastic with short and broadened ribs, and mild platyspondyly was seen. All phalanges and metacarpals were extremely short and the first metacarpal was triangular. Grigelioniene et al. (2011) noted that the radiographic findings were similar to those of the original case reported by al Gazali et al. (1996). Histologic analysis of bone tissue and the growth plate showed completely normal structure, suggesting that skeletal dysplasia of the al Gazali-type is a systemic disorder resulting in increased bone density and restricted growth of the skeleton.
Molecular Genetics
### Exclusion Studies
Using DNA from 2 unrelated female infants with al Gazali-type lethal skeletal dysplasia, of Swedish and Japanese origin, respectively, Grigelioniene et al. (2011) performed comparative genomic hybridization analysis but found no gene dosage abnormalities. Screening of all coding exons of the COL2A1 gene (120140) in the Swedish infant revealed no mutations.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Large head \- Wide anterior fontanel Ears \- Atretic auditory canals Eyes \- Corneal clouding SKELETAL \- Sclerotic bones Skull \- Occipital synchondrosis \- Wormian bones, multiple Spine \- Platyspondyly Limbs \- Mesomelic limb shortening, severe Hands \- Short metacarpals \- Short phalanges Feet \- Clubfoot, bilateral MISCELLANEOUS \- Neonatal lethality ▲ 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
|
LETHAL SHORT-LIMB SKELETAL DYSPLASIA, AL GAZALI TYPE
|
c1832435
| 7,564 |
omim
|
https://www.omim.org/entry/601356
| 2019-09-22T16:14:58 |
{"mesh": ["C537598"], "omim": ["601356"]}
|
A number sign (#) is used with this entry because of evidence that optic atrophy-10 (OPA10) with or without ataxia, mental retardation, and seizures can be caused by homozygous or compound heterozygous mutation in the RTN4IP1 gene (610502) on chromosome 6q21.
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Clinical Features
Angebault et al. (2015) studied a consanguineous Moroccan family in which a brother and sister, aged 52 years and 41 years, respectively, had low vision from early childhood without any other symptoms. Fundus examination showed moderate bilateral optic disc pallor, and optical coherence tomography (OCT) revealed a marked decrease in the thickness of the retinal nerve fiber layer temporally, suggestive of mitochondrial hereditary optic atrophy. Angebault et al. (2015) also studied 2 sisters, born of nonconsanguineous parents, who were 14 and 12 years old, respectively, and had severe bilateral optic neuropathy associated with nystagmus as well as a mild statokinetic cerebellar syndrome and learning disabilities. The older sister was more severely affected, with mild mental retardation and generalized seizures that began at age 3 years. Fundus examination in both sisters showed abnormal optic discs, which appeared to be small, with horizontal orientation, and pale over the entire surface, suggestive of hypoplasia. The thickness of the retinal nerve fiber layer was dramatically reduced in all quadrants. There was no detectable visual evoked potential, and optic tracts were thin on brain MRI, indicating severe alteration of the optic path. The brain was otherwise normal, as were cardiac and neuromuscular examinations.
Mapping
In a consanguineous Moroccan family in which 2 sibs had optic atrophy, Angebault et al. (2015) performed SNP genotyping and identified 4 homozygous regions, on chromosomes 1, 6, 18, and 22.
Molecular Genetics
In a consanguineous Moroccan family in which 2 sibs had optic atrophy, Angebault et al. (2015) performed exome sequencing and identified a homozygous missense mutation in the RTN4IP1 gene (R103H; 610502.0001) that segregated with disease. Screening of RTN4IP1 in a cohort of 240 European probands with inherited optic neuropathy revealed 2 simplex-case individuals of Roma origin who were homozygous for the same R103H mutation on the same haplotype, suggesting a founder effect. In addition, 2 sisters from a nonconsanguineous family who had optic neuropathy associated with ataxia, mental retardation, and seizures were compound heterozygous for R103H and a nonsense mutation in RTN4IP1 (K201X; 610502.0002).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Reduced visual acuity \- Photophobia \- Nystagmus (in some patients) \- Color vision impairment of red/green axis \- Optic disc pallor \- Central scotoma (in some patients) \- Decreased visual field sensitivity (in some patients) \- Reduced thickness of retinal nerve fiber layer \- Reduced or absent visual evoked potentials NEUROLOGIC Central Nervous System \- Ataxia, mild (in some patients) \- Mental retardation, mild (in some patients) \- Seizures, generalized (rare) MISCELLANEOUS \- Onset of visual dysfunction in early childhood MOLECULAR BASIS \- Caused by mutation in the reticulon 4-interacting protein-1 gene (RTN4IP1, 610502.0001 ) ▲ 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
|
OPTIC ATROPHY 10 WITH OR WITHOUT ATAXIA, MENTAL RETARDATION, AND SEIZURES
|
c4225227
| 7,565 |
omim
|
https://www.omim.org/entry/616732
| 2019-09-22T15:48:04 |
{"omim": ["616732"], "orphanet": ["98676"], "synonyms": ["Autosomal recessive non-syndromic optic atrophy"]}
|
A number sign (#) is used with this entry because of evidence that Popov-Chang syndrome (POPCHAS) is caused by heterozygous mutation in the YWHAZ gene (601288) on chromosome 8q22.
Description
Popov-Chang syndrome (POPCHAS) is a neurodevelopmental disorder characterized by global developmental delay apparent from infancy. Affected individuals have impaired intellectual development and poor or absent speech, as well as behavioral abnormalities. Most patients have significant facial dysmorphism, including coarse features, frontal bossing, and abnormal eye shape. Additional features are highly variable and can include seizures, short stature, feeding difficulties, and skin abnormalities (summary by Popov et al., 2019).
Clinical Features
Popov et al. (2019) reported 5 unrelated patients, ranging in age from 9 to 17 years, with variable manifestations of a neurodevelopmental disorder. All had global developmental delay, with mildly delayed walking ability, impaired intellectual development (IQ of 1 patient was 55), and poor or absent speech. Three had significant behavioral abnormalities, including autistic-like behavior, self-injurious behavior, fear of social interaction, and poor concentration. One patient had episodic hyperventilation associated with stressful situations. Three patients had seizures in childhood that remitted or could be controlled. Brain imaging tended to be normal, although one showed nonspecific cerebellar hypoplasia and cerebral atrophy. Four patients had notable but variable dysmorphic features, including frontal bossing, coarse facies, triangular face, ptosis, thin upper lip, thick lips, proptosis, long philtrum, and coarse hair. Photographs of the patients (figure 1) suggested abnormal eye shape, depressed nasal bridge with upturned tip, long nose, and mild hypertelorism. The photograph of patient 3 indicated milder dysmorphic features. A few patients had additional features, including poor feeding, short stature, poor growth, small hands and feet, and fifth finger clinodactyly. One patient (patient 1) had pulmonic stenosis, hydrocephalus, recurrent otitis media, hypogammaglobulinemia, lymphopenia, hyperkeratosis pilaris with dry skin, scoliosis, and hypertension, indicating a systemic disorder. None of the other 4 patients had cardiac malformations or skin involvement. One patient had cataracts and retinopathy.
Molecular Genetics
In 5 unrelated patients with POPCHAS, Popov et al. (2019) identified 5 different de novo heterozygous mutations in the YWHAZ gene (601288.0001-601288.0005), including 3 missense mutations, 1 nonsense mutation, and 1 frameshift mutation. The first patient was identified through a genome sequencing research study, and the other 4 patients were subsequently identified through GeneMatcher or through data-sharing of exome sequencing. Detailed functional studies of 1 of the missense variants (S230W; 601288.0001) in Xenopus indicated that this mutation resulted in a gain-of-function effect with increased activity of the Ras-Erk signaling pathway (see ANIMAL MODEL). Functional studies of the other variants and studies of patient cells were not performed.
Animal Model
Popov et al. (2019) found that injection of the S230W mutation into Xenopus embryos caused dark pigmentation, possibly reflecting changes in cell shape, as well as defects in head structure and shortened and bent body axis compared to controls. The abnormalities induced by the mutant gene were more severe than those induced by overexpression of the wildtype gene. Further studies showed that the mutant YWHAZ protein was able to rescue defects induced by dominant-negative FGFR1 (136350) and stimulated Raf-dependent Erk phosphorylation more efficiently than wildtype, consistent with a gain of function.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (in some patients) Other \- Failure to thrive (patient A) HEAD & NECK Head \- Frontal bossing Face \- Dysmorphic facial features (in most patients) \- Triangular face \- Long philtrum Ears \- Otitis media, recurrent (patient A) Eyes \- Ptosis \- Proptosis \- Abnormal eye morphology Nose \- Depressed nasal bridge \- Upturned nose \- Long nose Mouth \- Thin upper lip \- Thick lips CARDIOVASCULAR Heart \- Pulmonic stenosis (patient A) Vascular \- Hypertension (patient A) ABDOMEN Gastrointestinal \- Feeding difficulties (in some patients) \- Gastroesophageal reflux (patient A) SKELETAL \- Scoliosis (patient A) Hands \- Small hands \- Fifth finger clinodactyly Feet \- Small feet SKIN, NAILS, & HAIR Skin \- Hyperkeratosis (patient A) \- Dry skin (patient A) Hair \- Coarse hair NEUROLOGIC Central Nervous System \- Global developmental delay \- Delayed walking \- Impaired intellectual development \- Poor or absent speech \- Seizures, controlled (in some patients) \- Hydrocephalus (patient A) Behavioral Psychiatric Manifestations \- Autistic features \- Self-injurious behavior \- Fear during social interactions \- Poor concentration \- Hand stereotypies \- Hyperventilation when stressed (1 patient) IMMUNOLOGY \- Hypogammaglobulinemia (patient A) \- Lymphopenia (patient A) MISCELLANEOUS \- Onset in infancy \- Highly variable features \- Patient A was severely affected \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta isoform gene (YWHAZ, 601288.0001 ) ▲ 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
|
POPOV-CHANG SYNDROME
|
None
| 7,566 |
omim
|
https://www.omim.org/entry/618428
| 2019-09-22T15:41:59 |
{"omim": ["618428"], "synonyms": ["Alternative titles", "NEURODEVELOPMENTAL DISORDER WITH IMPAIRED SPEECH AND DYSMORPHIC FACIAL FEATURES"]}
|
Fragile X-associated primary ovarian insufficiency (FXPOI) is a condition that affects women and is characterized by reduced function of the ovaries. The ovaries are the female reproductive organs in which egg cells are produced. As a form of primary ovarian insufficiency, FXPOI can cause irregular menstrual cycles, early menopause, an inability to have children (infertility), and elevated levels of a hormone known as follicle stimulating hormone (FSH). FSH is produced in both males and females and helps regulate the development of reproductive cells (eggs in females and sperm in males). In females, the level of FSH rises and falls, but overall it increases as a woman ages. In younger women, elevated levels may indicate early menopause and fertility problems.
The severity of FXPOI is variable. The most severely affected women have overt POI (formerly called premature ovarian failure). These women have irregular or absent menstrual periods and elevated FSH levels before age 40. Overt POI often causes infertility. Other women have occult POI; they have normal menstrual periods but reduced fertility, and they may have elevated levels of FSH (in which case, it is called biochemical POI). The reduction in ovarian function caused by FXPOI results in low levels of the hormone estrogen, which leads to many of the common signs and symptoms of menopause, such as hot flashes, insomnia, and thinning of the bones (osteoporosis). Women with FXPOI undergo menopause an average of 5 years earlier than women without the condition.
## Frequency
An estimated 1 in 200 females has the genetic change that leads to FXPOI, although only about a quarter of them develop the condition. FXPOI accounts for about 4 to 6 percent of all cases of primary ovarian insufficiency in women.
## Causes
Mutations in the FMR1 gene increase a woman's risk of developing FXPOI. The FMR1 gene provides instructions for making a protein called FMRP, which helps regulate the production of other proteins. This protein plays a role in the functioning of nerve cells. It is also important for normal ovarian function, although the role is not fully understood.
Women with FXPOI have a mutation in which a DNA segment, known as a CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In women with FXPOI, however, the CGG segment is repeated 55 to 200 times. This mutation is known as an FMR1 gene premutation. Some studies show that women with about 44 to 54 CGG repeats, known as an intermediate (or gray zone) mutation, can also have features of FXPOI. An expansion of more than 200 repeats, a full mutation, causes a more serious disorder called fragile X syndrome, which is characterized by intellectual disability, learning problems, and certain physical features.
For unknown reasons, the premutation leads to the overproduction of abnormal FMR1 mRNA that contains the expanded repeat region. The FMR1 mRNA is the genetic blueprint for FMRP. Researchers believe that the high levels of mRNA cause the signs and symptoms of FXPOI. It is thought that the mRNA attaches to other proteins and keeps them from performing their functions. In addition, the repeats make producing FMRP from the blueprint more difficult, and as a result, people with the FMR1 gene premutation can have less FMRP than normal. A reduction of this protein is not thought to be involved in FXPOI. However, it may cause mild versions of the features seen in fragile X syndrome, such as prominent ears, anxiety, and mood swings.
### Learn more about the gene associated with Fragile X-associated primary ovarian insufficiency
* FMR1
## Inheritance Pattern
An increased risk of developing FXPOI is inherited in an X-linked dominant pattern. The FMR1 gene is located on the X chromosome, which is one of the two sex chromosomes. (The Y chromosome is the other sex chromosome.) The inheritance is dominant because one copy of the altered gene in each cell is sufficient to elevate the risk of developing FXPOI. In females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell can lead to the disorder. However, not all women who inherit an FMR1 premutation will develop FXPOI. Because males do not have ovaries, they are unaffected.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Fragile X-associated primary ovarian insufficiency
|
c4552079
| 7,567 |
medlineplus
|
https://medlineplus.gov/genetics/condition/fragile-x-associated-primary-ovarian-insufficiency/
| 2021-01-27T08:24:46 |
{"mesh": ["D016649"], "omim": ["311360"], "synonyms": []}
|
A rare ophthalmic disorder characterized by a usually congenital and unilateral round or oval, gray, white, or yellowish depression in the optic disc. There may be more than one pit present in one eye, and the anomaly is most commonly found in the inferotemporal region of the optic disc, although any sector may be involved. Patients are often asymptomatic, or may present with visual field defects, in particular paracentral arcuate scotoma connected to an enlarged blind spot. A number of patients develop serous macular detachment, with loss of vision typically becoming apparent in the third or fourth decade of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Optic disc pit
|
c0338504
| 7,568 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=519404
| 2021-01-23T18:01:37 |
{}
|
Disease where the kidneys fail to adequately filter waste products from the blood
Kidney failure
Other namesRenal failure, end-stage renal disease (ESRD), stage 5 chronic kidney disease[1]
A hemodialysis machine which is used to replace the function of the kidneys
SpecialtyNephrology
SymptomsLeg swelling, feeling tired, loss of appetite, confusion[2]
ComplicationsAcute: Uremia, high blood potassium, volume overload[3]
Chronic: Heart disease, high blood pressure, anemia[4][5]
TypesAcute kidney failure, chronic kidney failure[6]
CausesAcute: Low blood pressure, blockage of the urinary tract, certain medications, muscle breakdown, and hemolytic uremic syndrome.[6]
Chronic: Diabetes, high blood pressure, nephrotic syndrome, polycystic kidney disease[6]
Diagnostic methodAcute: Decreased urine production, increased serum creatinine[3]
Chronic:Glomerular filtration rate (GFR) < 15[1]
TreatmentAcute: Depends on the cause[7]
Chronic: Hemodialysis, peritoneal dialysis, kidney transplant[2]
FrequencyAcute: 3 per 1,000 per year[8]
Chronic: 1 per 1,000 (US)[1]
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys are functioning at less than 15% of normal levels.[2] Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible.[6] Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion.[2] Complications of acute and chronic failure include uremia, high blood potassium, and volume overload.[3] Complications of chronic failure also include heart disease, high blood pressure, and anemia.[4][5]
Causes of acute kidney failure include low blood pressure, blockage of the urinary tract, certain medications, muscle breakdown, and hemolytic uremic syndrome.[6] Causes of chronic kidney failure include diabetes, high blood pressure, nephrotic syndrome, and polycystic kidney disease.[6] Diagnosis of acute failure is often based on a combination of factors such as decreased urine production or increased serum creatinine.[3] Diagnosis of chronic failure is based on a glomerular filtration rate (GFR) of less than 15 or the need for renal replacement therapy.[1] It is also equivalent to stage 5 chronic kidney disease.[1]
Treatment of acute failure depends on the underlying cause.[7] Treatment of chronic failure may include hemodialysis, peritoneal dialysis, or a kidney transplant.[2] Hemodialysis uses a machine to filter the blood outside the body.[2] In peritoneal dialysis specific fluid is placed into the abdominal cavity and then drained, with this process being repeated multiple times per day.[2] Kidney transplantation involves surgically placing a kidney from someone else and then taking immunosuppressant medication to prevent rejection.[2] Other recommended measures from chronic disease include staying active and specific dietary changes.[2]
In the United States acute failure affects about 3 per 1,000 people a year.[8] Chronic failure affects about 1 in 1,000 people with 3 per 10,000 people newly developing the condition each year.[1][9] Acute failure is often reversible while chronic failure often is not.[6] With appropriate treatment many with chronic disease can continue working.[2]
## Contents
* 1 Classification
* 1.1 Acute kidney failure
* 1.2 Chronic kidney failure
* 1.3 Acute-on-chronic kidney failure
* 2 Signs and symptoms
* 3 Causes
* 3.1 Acute kidney injury
* 3.2 Chronic kidney failure
* 3.3 Genetic predisposition
* 4 Diagnostic approach
* 4.1 Measurement for CKD
* 4.2 Use of the term uremia
* 5 Treatment
* 5.1 Diet
* 5.2 Slowing progression
* 6 References
* 7 External links
## Classification[edit]
See also: Hepatorenal syndrome
Kidney failure can be divided into two categories: acute kidney failure or chronic kidney failure. The type of renal failure is differentiated by the trend in the serum creatinine; other factors that may help differentiate acute kidney failure from chronic kidney failure include anemia and the kidney size on sonography as chronic kidney disease generally leads to anemia and small kidney size.
### Acute kidney failure[edit]
Main article: Acute kidney injury
Acute kidney injury (AKI), previously called acute renal failure (ARF),[10][11] is a rapidly progressive loss of renal function,[12] generally characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults,[13] less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); and fluid and electrolyte imbalance. AKI can result from a variety of causes, generally classified as prerenal, intrinsic, and postrenal. Many people diagnosed with paraquat intoxication experience AKI, sometimes requiring hemodialysis.[citation needed] The underlying cause must be identified and treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes.
### Chronic kidney failure[edit]
Main article: Chronic kidney disease
Illustration of a kidney from a person with chronic renal failure
Chronic kidney disease (CKD) can also develop slowly and, initially, show few symptoms.[14] CKD can be the long term consequence of irreversible acute disease or part of a disease progression.
### Acute-on-chronic kidney failure[edit]
Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic kidney failure (AoCRF). The acute part of AoCRF may be reversible, and the goal of treatment, as with AKI, is to return the person to baseline kidney function, typically measured by serum creatinine. Like AKI, AoCRF can be difficult to distinguish from chronic kidney disease if the person has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.
## Signs and symptoms[edit]
Symptoms can vary from person to person. Someone in early stage kidney disease may not feel sick or notice symptoms as they occur. When the kidneys fail to filter properly, waste accumulates in the blood and the body, a condition called azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the disease progresses, symptoms become noticeable (if the failure is of sufficient degree to cause symptoms). Kidney failure accompanied by noticeable symptoms is termed uraemia.[15]
Symptoms of kidney failure include the following:[15][16][17][18]
* High levels of urea in the blood, which can result in:
* Vomiting or diarrhea (or both) may lead to dehydration
* Nausea
* Weight loss
* Nocturnal urination (nocturia)
* More frequent urination, or in greater amounts than usual, with pale urine
* Less frequent urination, or in smaller amounts than usual, with dark coloured urine
* Blood in the urine
* Pressure, or difficulty urinating
* Unusual amounts of urination, usually in large quantities
* A buildup of phosphates in the blood that diseased kidneys cannot filter out may cause:
* Itching
* Bone damage
* Nonunion in broken bones
* Muscle cramps (caused by low levels of calcium which can be associated with hyperphosphatemia)
* A buildup of potassium in the blood that diseased kidneys cannot filter out (called hyperkalemia) may cause:
* Abnormal heart rhythms
* Muscle paralysis[19]
* Failure of kidneys to remove excess fluid may cause:
* Swelling of the hands, legs, ankles, feet, or face
* Shortness of breath due to extra fluid on the lungs (may also be caused by anemia)
* Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause:
* Pain in the back or side
* Healthy kidneys produce the hormone erythropoietin that stimulates the bone marrow to make oxygen-carrying red blood cells. As the kidneys fail, they produce less erythropoietin, resulting in decreased production of red blood cells to replace the natural breakdown of old red blood cells. As a result, the blood carries less hemoglobin, a condition known as anemia. This can result in:
* Feeling tired or weak
* Memory problems
* Difficulty concentrating
* Dizziness
* Low blood pressure
* Normally proteins are too large to pass through the kidneys. However they are able to pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occurred,[20] after which symptoms include:
* Foamy or bubbly urine
* Swelling in the hands, feet, abdomen, and face
* Other symptoms include:
* Appetite loss, which may include a bad taste in the mouth
* Difficulty sleeping
* Darkening of the skin
* Excess protein in the blood
* With high doses of penicillin, people with kidney failure may experience seizures[21]
## Causes[edit]
### Acute kidney injury[edit]
Acute kidney injury (previously known as acute renal failure) – or AKI – usually occurs when the blood supply to the kidneys is suddenly interrupted or when the kidneys become overloaded with toxins. Causes of acute kidney injury include accidents, injuries, or complications from surgeries in which the kidneys are deprived of normal blood flow for extended periods of time. Heart-bypass surgery is an example of one such procedure.
Drug overdoses, accidental or from chemical overloads of drugs such as antibiotics or chemotherapy, along with bee stings[22] may also cause the onset of acute kidney injury. Unlike chronic kidney disease, however, the kidneys can often recover from acute kidney injury, allowing the person with AKI to resume a normal life. People suffering from acute kidney injury require supportive treatment until their kidneys recover function, and they often remain at increased risk of developing future kidney failure.[23]
Among the accidental causes of renal failure is the crush syndrome, when large amounts of toxins are suddenly released in the blood circulation after a long compressed limb is suddenly relieved from the pressure obstructing the blood flow through its tissues, causing ischemia. The resulting overload can lead to the clogging and the destruction of the kidneys. It is a reperfusion injury that appears after the release of the crushing pressure. The mechanism is believed to be the release into the bloodstream of muscle breakdown products – notably myoglobin, potassium, and phosphorus – that are the products of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions). The specific action on the kidneys is not fully understood, but may be due in part to nephrotoxic metabolites of myoglobin.
### Chronic kidney failure[edit]
Chronic kidney failure has numerous causes. The most common causes of chronic failure are diabetes mellitus and long-term, uncontrolled hypertension.[24] Polycystic kidney disease is another well-known cause of chronic failure. The majority of people afflicted with polycystic kidney disease have a family history of the disease. Other genetic illnesses cause kidney failure, as well.
Overuse of common drugs such as ibuprofen, and acetaminophen (paracetamol) can also cause chronic kidney failure.[25]
Some infectious disease agents, such as hantavirus, can attack the kidneys, causing kidney failure.[26]
### Genetic predisposition[edit]
The APOL1 gene has been proposed as a major genetic risk locus for a spectrum of nondiabetic renal failure in individuals of African origin, these include HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies.[27] Two western African variants in APOL1 have been shown to be associated with end stage kidney disease in African Americans and Hispanic Americans.[28][29]
## Diagnostic approach[edit]
### Measurement for CKD[edit]
Stages of kidney failure
Chronic kidney failure is measured in five stages, which are calculated using the person's GFR, or glomerular filtration rate. Stage 1 CKD is mildly diminished renal function, with few overt symptoms. Stages 2 and 3 need increasing levels of supportive care from their medical providers to slow and treat their renal dysfunction. People with stage 4 and 5 kidney failure usually require preparation towards active treatment in order to survive. Stage 5 CKD is considered a severe illness and requires some form of renal replacement therapy (dialysis) or kidney transplant whenever feasible.
Glomerular filtration rate
A normal GFR varies according to many factors, including sex, age, body size and ethnic background. Renal professionals consider the glomerular filtration rate (GFR) to be the best overall index of kidney function.[30] The National Kidney Foundation offers an easy to use on-line GFR calculator[31] for anyone who is interested in knowing their glomerular filtration rate. (A serum creatinine level, a simple blood test, is needed to use the calculator.)
### Use of the term uremia[edit]
Before the advancement of modern medicine, renal failure was often referred to as uremic poisoning. Uremia was the term for the contamination of the blood with urea. It is the presence of an excessive amount of urea in blood. Starting around 1847, this included reduced urine output, which was thought to be caused by the urine mixing with the blood instead of being voided through the urethra.[citation needed] The term uremia is now used for the illness accompanying kidney failure.[32]
## Treatment[edit]
The treatment of acute kidney injury depends on the cause.[7] The treatment of chronic kidney failure may include renal replacement therapy: hemodialysis, peritoneal dialysis, or kidney transplant[2]
### Diet[edit]
In non-diabetics and people with type 1 diabetes, a low protein diet is found to have a preventive effect on progression of chronic kidney disease. However, this effect does not apply to people with type 2 diabetes.[33] A whole food, plant-based diet may help some people with kidney disease.[34] A high protein diet from either animal or plant sources appears to have negative effects on kidney function at least in the short term.[35]
### Slowing progression[edit]
People who receive earlier referrals to a nephrology specialist, meaning a longer time before they must start dialysis, have a shorter initial hospitalization and reduced risk of death after the start of dialysis.[36] Other methods of reducing disease progression include minimizing exposure to nephrotoxins such as NSAIDs and intravenous contrast.[37]
## References[edit]
1. ^ a b c d e f Cheung, Alfred K. (2005). Primer on Kidney Diseases. Elsevier Health Sciences. p. 457. ISBN 1416023127.
2. ^ a b c d e f g h i j k "Kidney Failure". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 11 November 2017.
3. ^ a b c d Blakeley, Sara (2010). Renal Failure and Replacement Therapies. Springer Science & Business Media. p. 19. ISBN 9781846289378.
4. ^ a b Liao, Min-Tser; Sung, Chih-Chien; Hung, Kuo-Chin; Wu, Chia-Chao; Lo, Lan; Lu, Kuo-Cheng (2012). "Insulin Resistance in Patients with Chronic Kidney Disease". Journal of Biomedicine and Biotechnology. 2012: 1–5. doi:10.1155/2012/691369. PMC 3420350. PMID 22919275.
5. ^ a b "Kidney Failure". MedlinePlus. Retrieved 11 November 2017.
6. ^ a b c d e f g "What is renal failure?". Johns Hopkins Medicine. Archived from the original on 18 June 2017. Retrieved 18 December 2017.
7. ^ a b c Clatworthy, Menna (2010). Nephrology: Clinical Cases Uncovered. John Wiley & Sons. p. 28. ISBN 9781405189903.
8. ^ a b Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 37. ISBN 9780323529570.
9. ^ Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 294. ISBN 9780323529570.
10. ^ Moore, EM; Bellomo, R; Nichol, AD (2012). "The meaning of acute kidney injury and its relevance to intensive care and anaesthesia". Anaesthesia and Intensive Care. 40 (6): 929–48. doi:10.1177/0310057X1204000604. PMID 23194202.
11. ^ Ricci, Zaccaria; Ronco, Claudio (2012). "New insights in acute kidney failure in the critically ill". Swiss Medical Weekly. 142: w13662. doi:10.4414/smw.2012.13662. PMID 22923149.
12. ^ A.D.A.M. Medical Encyclopedia (2012). "Acute kidney failure". U.S. National Library of Medicine. Retrieved 1 January 2013.
13. ^ Klahr, Saulo; Miller, Steven B. (1998). "Acute Oliguria". New England Journal of Medicine. 338 (10): 671–75. doi:10.1056/NEJM199803053381007. PMID 9486997.
14. ^ Medline Plus (2011). "Chronic kidney disease". A.D.A.M. Medical Encyclopedia. National Institutes of Health. Retrieved 1 January 2013.
15. ^ a b Dr Per Grinsted (2005-03-02). "Kidney failure (renal failure with uremia, or azotaemia)". Retrieved 2009-05-26.
16. ^ Dr Andy Stein (2007-07-01). Understanding Treatment Options For Renal Therapy. Deerfield, Illinois: Baxter International Inc. p. 6. ISBN 978-1-85959-070-6.
17. ^ The PD Companion. Deerfield, Illinois: Baxter International Inc. 2008-05-01. pp. 14–15. 08/1046R. Archived from the original on 2010-06-25. Retrieved 2010-07-12.
18. ^ Amgen Inc. (2009). "10 Symptoms of Kidney Disease". Retrieved 2009-05-26.
19. ^ MedicineNet, Inc. (2008-07-03). "Hyperkalemia". Retrieved 2009-05-26.
20. ^ Lee A. Hebert, M.D., Jeanne Charleston, R.N. and Edgar Miller, M.D. (2009). "Proteinuria". Archived from the original on 2011-05-05. Retrieved 2011-03-24.CS1 maint: multiple names: authors list (link)
21. ^ Katzung, Bertram G. (2007). Basic and Clinical Pharmacology (10th ed.). New York, NY: McGraw Hill Medical. p. 733. ISBN 978-0-07-145153-6.
22. ^ da Silva, Geraldo Bezerra; Vasconcelos, Adolfo Gomes; Rocha, Amanda Maria Timbó; de Vasconcelos, Vanessa Ribeiro; de Barros, João; Fujishima, Julye Sampaio; Ferreira, Nathália Barros; Barros, Elvino José Guardão; Daher, Elizabeth De Francesco (1 June 2017). "Acute kidney injury complicating bee stings – a review". Revista do Instituto de Medicina Tropical de São Paulo. 59: e25. doi:10.1590/S1678-9946201759025. PMC 5459532. PMID 28591253.
23. ^ National Kidney and Urologic Diseases Information Clearinghouse (2012). "The Kidneys and How They Work". National Institute of Diabetes and Digestive and Kidney Diseases. Archived from the original on 2 May 2015. Retrieved 1 January 2013.
24. ^ Kes, Petar; Basić-Jukić, Nikolina; Ljutić, Dragan; Brunetta-Gavranić, Bruna (2011). "Uloga arterijske hipertenzije u nastanku kroničnog zatajenja bubrega" [The role of arterial hypertension in the development of chronic renal failure] (PDF). Acta Medica Croatica (in Croatian). 65 (Suppl 3): 78–84. PMID 23120821. Archived from the original (PDF) on 2013-07-19.
25. ^ Perneger, Thomas V.; Whelton, Paul K.; Klag, Michael J. (1994). "Risk of Kidney Failure Associated with the Use of Acetaminophen, Aspirin, and Nonsteroidal Antiinflammatory Drugs". New England Journal of Medicine. 331 (25): 1675–79. doi:10.1056/NEJM199412223312502. PMID 7969358.
26. ^ Appel, Gerald B; Mustonen, Jukka (2012). "Renal involvement with hantavirus infection (hemorrhagic fever with renal syndrome)". UpToDate. Retrieved 1 January 2013.
27. ^ Bostrom, M. A.; Freedman, B. I. (2010). "The Spectrum of MYH9-Associated Nephropathy". Clinical Journal of the American Society of Nephrology. 5 (6): 1107–13. doi:10.2215/CJN.08721209. PMC 4890964. PMID 20299374.
28. ^ Genovese, Giulio; Friedman, David J.; Ross, Michael D.; Lecordier, Laurence; Uzureau, Pierrick; Freedman, Barry I.; Bowden, Donald W.; Langefeld, Carl D.; et al. (2010). "Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans". Science. 329 (5993): 841–45. Bibcode:2010Sci...329..841G. doi:10.1126/science.1193032. PMC 2980843. PMID 20647424.
29. ^ Tzur, Shay; Rosset, Saharon; Shemer, Revital; Yudkovsky, Guennady; Selig, Sara; Tarekegn, Ayele; Bekele, Endashaw; Bradman, Neil; et al. (2010). "Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene". Human Genetics. 128 (3): 345–50. doi:10.1007/s00439-010-0861-0. PMC 2921485. PMID 20635188.
30. ^ Fadem, Stephen Z., M.D., FACP, FASN. Calculators for HealthCare Professionals. National Kidney Foundation. 13 Oct 2008
31. ^ "GFR calculator". Kidney.org. Retrieved 2011-09-25.
32. ^ Meyer, Timothy W.; Hostetter, Thomas H. (2007). "Uremia". New England Journal of Medicine. 357 (13): 1316–25. doi:10.1056/NEJMra071313. PMID 17898101.
33. ^ Rughooputh, Mahesh Shumsher; Zeng, Rui; Yao, Ying; Sands, Jeff M (28 December 2015). "Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients, but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials Using Glomerular Filtration Rate as a Surrogate". PLOS ONE. 10 (12): e0145505. Bibcode:2015PLoSO..1045505R. doi:10.1371/journal.pone.0145505. PMC 4692386. PMID 26710078.
34. ^ Chauveau, Philippe; Combe, Christian; Fouque, Denis; Aparicio, Michel (November 2013). "Vegetarianism: Advantages and Drawbacks in Patients With Chronic Kidney Diseases". Journal of Renal Nutrition. 23 (6): 399–405. doi:10.1053/j.jrn.2013.08.004. PMID 24070587.
35. ^ Bernstein, Adam M.; Treyzon, Leo; Li, Zhaoping (April 2007). "Are High-Protein, Vegetable-Based Diets Safe for Kidney Function? A Review of the Literature". Journal of the American Dietetic Association. 107 (4): 644–650. doi:10.1016/j.jada.2007.01.002. PMID 17383270.
36. ^ Smart, Neil A; Dieberg, Gudrun; Ladhani, Maleeka; Titus, Thomas (18 June 2014). "Early referral to specialist nephrology services for preventing the progression to end-stage kidney disease". Cochrane Database of Systematic Reviews (6): CD007333. doi:10.1002/14651858.CD007333.pub2. PMID 24938824.
37. ^ Dirkx, Tonja C.; Woodell, Tyler; Watnick, Suzanne (2017). Papadakis, Maxine A.; McPhee, Stephen J.; Rabow, Michael W. (eds.). Current Medical Diagnosis & Treatment 2018. New York, NY: McGraw-Hill Education.
## External links[edit]
Classification
D
* ICD-10: N17–N19
* ICD-9-CM: 584–585
* MeSH: D051437
* DiseasesDB: 26060
* v
* t
* e
Kidney disease
Glomerular disease
* See Template:Glomerular disease
Tubules
* Renal tubular acidosis
* proximal
* distal
* Acute tubular necrosis
* Genetic
* Fanconi syndrome
* Bartter syndrome
* Gitelman syndrome
* Liddle's syndrome
Interstitium
* Interstitial nephritis
* Pyelonephritis
* Balkan endemic nephropathy
Vascular
* Renal artery stenosis
* Renal ischemia
* Hypertensive nephropathy
* Renovascular hypertension
* Renal cortical necrosis
General syndromes
* Nephritis
* Nephrosis
* Renal failure
* Acute renal failure
* Chronic kidney disease
* Uremia
Other
* Analgesic nephropathy
* Renal osteodystrophy
* Nephroptosis
* Abderhalden–Kaufmann–Lignac syndrome
* Diabetes insipidus
* Nephrogenic
* Renal papilla
* Renal papillary necrosis
* Major calyx/pelvis
* Hydronephrosis
* Pyonephrosis
* Reflux nephropathy
* v
* t
* e
Organ failure
General
* Heart failure
* Respiratory failure
* Liver failure
* Acute
* Chronic
* Renal failure
* Acute
* Chronic
* Encephalopathy
Multiple
* Multiple organ dysfunction 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
|
Kidney failure
|
c0035078
| 7,569 |
wikipedia
|
https://en.wikipedia.org/wiki/Kidney_failure
| 2021-01-18T18:36:41 |
{"mesh": ["D051437"], "umls": ["C1565489", "C1839604", "C0035078"], "wikidata": ["Q476921"]}
|
A number sign (#) is used with this entry because of evidence that congenital nongoitrous hypothyroidism-2 (CHNG2) is caused by heterozygous mutation in the PAX8 gene (167415) on chromosome 2q14.
For a general phenotypic description and a discussion of genetic heterogeneity of congenital nongoitrous hypothyroidism, see 275200.
Description
In 80 to 85% of cases, congenital hypothyroidism is associated with, and presumably is a consequence of, thyroid dysgenesis. In these cases, the thyroid gland can be absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia). When thyroid hormone therapy is not initiated within the first 2 months of life, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (Macchia et al., 1998).
Clinical Features
Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism, accounting for 85% of cases (Fisher, 1983). Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue. Athyreosis is defined as the absence of any detectable thyroid tissue.
Athyreotic cretinism is not as clearly mendelizing as is goitrous cretinism. There is some familial aggregation which may be of the same type as is seen with many common congenital malformations. It is noteworthy that whether goiter is present or not is dependent on age and treatment. Under certain circumstances a patient who has the same defect as in one of the types of goitrous cretinism may appear to be athyreotic (Beierwaltes, 1964).
In an inbred Amish group, Cross et al. (1968) observed 2 sisters with cretinism and the Kocher-Debre-Semelaigne syndrome (myotonia and muscular pseudohypertrophy). Although no thyroid was palpable, sensitive scanning techniques showed the presence of a small amount of thyroid tissue in the neck. Thus, 'agoitrous cretinism' is a better designation than athyreotic cretinism.
Kaplan et al. (1977) described 2 nonconsanguineous Ashkenazi Jewish families in each of which a brother and sister had hypothyroidism associated with ectopia and hypoplasia of the thyroid. They cited another report of familial occurrence of ectopic thyroid (Mahoney and Igo, 1974). Hypothyroidism may not become evident until late childhood or adolescence. Cases reported by Gabr (1962) and Little et al. (1965) had severe cretinism. Thyroid-stimulating hormone was elevated. Rosenberg and Gilboa (1980) described 2 sisters with sublingual thyroid glands and hypothyroidism. A brother had agenesis of the left lobe of the thyroid but normal thyroid function. Donegan and Wood (1985) reported intratracheal thyroid in 2 sisters. In 1, the ectopic thyroid was involved in follicular carcinoma.
A possible relationship to inability to taste PTC (171200) was proposed by Shepard and Gartler (1960), Fraser (1961), Shepard and Andersen (1965). Both newborn athyreotic hypothyroidism and inability to taste PTC have a lower frequency in blacks than in whites. Nearly all patients with athyreotic hypothyroidism are PTC nontasters.
Scriver (2002) reported that he and his colleagues, in an unpublished study, found no disproportionate association of PTC taste type with the nonmendelian form of congenital hypothyroidism.
De Zegher et al. (1988) noted an association between growth hormone deficiency and congenital hypothyroidism. They pointed out the necessity for careful monitoring of growth in children treated for congenital hypothyroidism.
Eberle (1993) reported the case of a boy, almost 12 years old, with short stature, dysplastic epiphyses, and vertebral anomalies thought to be due to spondyloepiphyseal dysplasia. Because of facial appearance, Aarskog syndrome (305400) had been suggested. The importance of recognizing the true nature of this patient's disorder as congenital hypothyroidism is obvious.
Pathogenesis
Blizzard et al. (1960) suggested that maternal autoantibodies may be responsible for destruction of the fetal thyroid. They observed the birth of 2 successive cretins from a mother with autoantibodies. Antibodies were implicated in the familial cases of Sutherland et al. (1960). This could be a nongenetic mechanism of familial occurrence of athyreotic cretinism.
Inheritance
Although these cases, like those of panhypopituitarism, are usually sporadic, out of 152 cases reported by Wilkins (1965), 1 sib pair was found. Ainger and Kelley (1955) reported 3 sibs, as did Sutherland et al. (1960). Females are affected about twice as often as males. Greig et al. (1966) described 2 pairs of monozygotic twins, all of whom were affected. One pair was considered athyreotic and the other had residual thyroid and ectopic tissue, respectively. The authors, who referred to the condition as thyroid dysgenesis, also described affected mother and child; the father was unknown and presumably incest was possible, making recessive inheritance likely. Since thyroid-stimulating hormone (188540) and the effects of thyrotropin-releasing hormone (613879) were not tested in the cases of Cross et al. (1968), these and others of the reported cases of 'athyreotic cretinism,' may be instances of 'pituitary cretinism,' i.e., thyrotropin deficiency (275100).
Castanet et al. (2000) reported that 2% of congenital hypothyroidism patients with thyroid dysgenesis have a positive familial history. Castanet et al. (2001) described the clinical characteristics of these familial cases and compared them with sporadic cases. Using the French national population-based registry of the first 19-year screening program, they identified 67 patients with a positive family history of congenital hypothyroidism with thyroid dysgenesis (at least 2 affected family members) belonging to 32 multiplex families. Families were identified with ectopic gland (12), athyreosis (7), or both (13). Comparison of familial with isolated cases showed a similar etiologic diagnosis distribution of congenital hypothyroidism (40% vs 33% for athyreosis and 60% vs 67% for ectopic thyroid gland, respectively), whereas a significantly lower predominance of females was found in familial than in isolated cases. Extrathyroidal congenital malformations were found with a similarly higher incidence in familial and isolated congenital hypothyroidism populations compared with the general population (respectively, 9% and 8.2% vs 2.5%). The authors concluded that, although familial cases represent a minority of cases of congenital hypothyroidism caused by thyroid dysgenesis, they were observed in a significantly higher proportion (greater than 15-fold) than would be expected from chance alone. This familial clustering, including athyreosis and ectopic thyroid gland, strongly suggests that genetic factors could be involved in thyroid dysgenesis with a common underlying mechanism for both etiologic groups. Moreover, the high proportion of extrathyroidal congenital malformations in a population affected by congenital hypothyroidism due to thyroid dysgenesis suggests that the potential genetic factors involved in thyroid gland organogenesis are also involved in the development of other organs.
Leger et al. (2002) investigated thyroid developmental abnormalities in first-degree relatives of congenital hypothyroidism children with thyroid dysgenesis, an anomaly which, when present, is sometimes asymptomatic. Thyroid ultrasonography and function were evaluated among 241 first-degree relatives of 84 isolated congenital hypothyroidism children with thyroid dysgenesis. The results were compared with those of an unselected control population of 217. In 19 individuals (7.9% of cases) belonging to 18 families (21.4%), 21 cases of thyroid developmental abnormalities were detected, whereas only 2 subjects (0.9%) were affected in controls (P less than 0.001). These 21 thyroid developmental abnormalities included 14 cases of thyroglossal duct cysts (188455), 3 cases of additional thyroid tissue with presence of a pyramidal lobe, 3 cases of thyroid hemiagenesis, and 1 case of ectopic thyroid tissue. All of these subjects showed normal thyroid function and belonged to nuclear families of congenital hypothyroidism children with athyreosis (8), ectopic thyroid tissue (9), or hemiagenesis (1). A segregation analysis led to the conclusion that thyroid developmental abnormalities are compatible with an autosomal dominant mode of inheritance with a low penetrance estimated at 21% for asymptomatic thyroid developmental abnormalities and a probability of less than 7% of developing congenital hypothyroidism for a carrier of the susceptibility allele. The authors concluded that these observations support the hypothesis of a common genetic component of the disorder with heterogeneous phenotypes.
Perry et al. (2002) noted that since the advent of biochemical screening for congenital hypothyroidism, most reported instances of monozygotic twins with thyroid dysgenesis had been discordant, and most were missed on neonatal screening, presumably due to fetal blood mixing. Perry et al. (2002) hypothesized that there may be a bias leading to preferential reporting of discordant twins and/or of false-negative screening results. In a systematic search for twins in 2 congenital hypothyroidism screening centers, Quebec and Brussels, that used a primary TSH approach, they identified a total of 16 pairs of twins, all discordant for congenital hypothyroidism. These included 5 monozygotic pairs with thyroid dysgenesis. The median increase in TSH between screening and diagnosis was 7-fold in monozygotic twins versus 2-fold in matched singletons, suggesting fetal blood mixing between the twins. Thus, discordance for thyroid dysgenesis appears to be the rule in monozygotic twins, and fetal blood mixing may result in delayed or missed diagnoses. Perry et al. (2002) concluded that a second sample for congenital hypothyroidism screening at 14 days of age should be considered for all same sex twins and that thyroid dysgenesis generally results from epigenetic phenomena, early somatic mutations, or postzygotic stochastic events.
Molecular Genetics
In 3 infants with congenital hypothyroidism and thyroid hypoplasia, Macchia et al. (1998) identified heterozygosity for 3 different mutations in the PAX8 gene (167415.0002-167415.0004). The first infant had thyroid ectopy and reduced gland size with elevated levels of TSH and thyroglobulin but thyroxin (T4) levels in the normal range. The second infant was diagnosed with thyroid hypoplasia and had TSH levels 100-fold above normal and T4 levels well below normal. The third infant had severe thyroid hypoplasia (cystic thyroid rudiment) and an elevated TSH with below-normal thyroid hormone levels. His mother and sister were heterozygous for the same mutation but displayed clinical variability: the mother had been diagnosed with hypothyroidism at age 10 and had a hypoplastic thyroid gland, whereas the sister had a thyroid of a size at the lower limit of normal, with normal thyroid hormone levels but high TSH values.
In a mother and daughter with congenital hypothyroidism and aplasia and eutopic hypoplasia of the thyroid gland, respectively, Vilain et al. (2001) identified heterozygosity for a mutation in the PAX8 gene (167415.0005). An unaffected daughter in the family did not carry the mutation.
In a girl with overt congenital hypothyroidism and a hypoplastic thyroid gland, Congdon et al. (2001) identified heterozygosity for a mutation in the PAX8 gene (167415.0007). Her mother, who was also heterozygous for the mutation, had a thyroid gland of normal size and displayed no signs or symptoms of hypothyroidism until age 31, at which time she was diagnosed with mild autoimmune hypothyroidism with positive antibodies. The unaffected father and brother did not have the mutation. Congdon et al. (2001) suggested that PAX8 mutations may have incomplete penetrance or variable expressivity, and noted that phenotypic variability was also reported in the family studied by Macchia et al. (1998).
In 2 children who were found to have congenital hypothyroidism on neonatal screening and their father, Meeus et al. (2004) identified heterozygosity for a mutation in the PAX8 gene (167415.0006). Although neonatal scintigraphy revealed an in situ thyroid gland of normal shape and size in the brother and sister, both were later found to have hypoplastic glands, at age 11.5 and 3.5 years, respectively. The father had been diagnosed with hypothyroidism at age 3; at age 25 his thyroid gland was nonpalpaple and echography showed a 'small amount of thyroid tissue (thickness less than 0.5 cm) in normal position', suggestive of thyroid hypoplasia. The father was also found to have agenesis of the right kidney, and Meeus et al. (2004) noted that PAX8 is also strongly expressed in the kidney during development.
Grasberger et al. (2005) studied 7 members of a nonconsanguineous family who were hypothyroid with an apparent autosomal dominant mode of inheritance but who had striking variability in their initial clinical presentation. The proband and her brother were found to have an elevated TSH and low free T4 on neonatal screening; both had a thyroid gland of normal shape and position on scintigraphy. Their affected mother had been diagnosed with mild hypothyroidism after routine blood testing at age 37. A female cousin was also discovered to have a very elevated TSH and very low free T4 on neonatal screening; she had no thyroidal or ectopic uptake of radioiodine on scintigraphy, consistent with athyreosis. Her 5-year-old brother was subsequently screened and found to have an elevated TSH with normal free T4; their father had been diagnosed with hypothyroidism at age 5. The 67-year-old grandmother of the cousins was screened as a part of this study and diagnosed with 'moderate thyroid failure.' Linkage analysis showed haplotype sharing of the affected family members at the PAX8 locus; sequence analysis revealed heterozygosity for a mutation in the PAX8 gene (167415.0008) in affected family members.
De Felice and Di Lauro (2004) reviewed the development of the thyroid gland and the genetic molecular mechanisms leading to thyroid dysgenesis.
Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder.
### Exclusion Studies
Lapi et al. (1997) screened 61 patients with congenital hypothyroidism for mutations in the TTF1 gene using SSCP and did not identify any mutations. Using direct sequencing, they rescreened 22 patients from that group who had thyroid agenesis but again detected no mutations in TTF1. Lapi et al. (1997) concluded that mutations in the TTF1 gene are not a frequent cause of congenital hypothyroidism.
Investigating the PAX8, TTF1 (600635), FOXE1, and TSHR (603372) genes, all of which were implicated in thyroid development, Castanet et al. (2005) performed linkage analysis followed by mutation analysis in 19 multiplex TD families. The lod score results failed to prove linkage between any of the 4 genes and the TD phenotype, whatever the postulated mode of inheritance. Extended haplotypes confirmed by mutation analysis showed that the 4 genes were excluded in 5 of the 19 families, demonstrating the relevance of other genes in TD.
Population Genetics
The incidence of newborn athyreotic hypothyroidism in whites and blacks is strikingly different: 1 in 5,526 and 1 in 32,377, respectively (Brown et al., 1981). The relative rarity in blacks has long been recognized (Childs and Gardner, 1954).
A female predominance has been identified (Goujard et al., 1981).
Nomenclature
'Athyreotic cretinism' is an unsatisfactory term which shares the negative connotations of 'congenital deafmutism.' Both designations refer to the untreated state; hence the alternative terms listed in the title, any one of which is preferable to athyreotic cretinism.
INHERITANCE \- Autosomal dominant GROWTH Other \- Poor feeding \- Delayed growth HEAD & NECK Head \- Large posterior fontanel Mouth \- Macroglossia CARDIOVASCULAR Heart \- Bradycardia RESPIRATORY Nasopharynx \- Noisy breathing \- Nasal stuffiness ABDOMEN External Features \- Abdominal distention \- Umbilical hernia Biliary Tract \- Prolonged physiologic hyperbilirubinemia Gastrointestinal \- Constipation SKELETAL \- Delayed skeletal maturation SKIN, NAILS, & HAIR Skin \- Dry \- Puffy NEUROLOGIC Central Nervous System \- Hypothermia \- Lethargy \- Hypotonia VOICE \- Hoarse cry ENDOCRINE FEATURES \- Ectopic thyroid \- Hypoplastic thyroid \- Thyroid agenesis \- Goiter LABORATORY ABNORMALITIES \- Low T4 \- High TSH MISCELLANEOUS \- Maternal autoantibodies \- Female to male ratio 2:1 \- Rare in blacks MOLECULAR BASIS \- Caused by mutation in the paired box homeotic gene 8 (PAX8, 167415.0002 ) ▲ 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
|
HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 2
|
c0151516
| 7,570 |
omim
|
https://www.omim.org/entry/218700
| 2019-09-22T16:29:14 |
{"doid": ["0070124"], "mesh": ["D050033"], "omim": ["218700"], "orphanet": ["95720", "95719", "95713", "95712"], "synonyms": ["Alternative titles", "THYROID DYSGENESIS", "THYROID AGENESIS", "THYROID HYPOPLASIA", "THYROID, ECTOPIC", "HYPOTHYROIDISM, CONGENITAL, DUE TO THYROID DYSGENESIS", "HYPOTHYROIDISM, ATHYREOTIC", "ATHYREOTIC HYPOTHYROIDISM", "RESISTANCE TO THYROTROPIN", "THYROTROPIN RESISTANCE"]}
|
Trisomy 20p is a chromosomal disorder resulting from duplication of all or part of the short arm of chromosome 20. It is mostly characterized by normal growth, mild to moderate intellectual disability, speech delay, poor coordination and evocative facial features.
## Epidemiology
Trisomy 20p is rarely reported. To date, fewer than 40 patients have been described.
## Clinical description
Clinical manifestations linked to trisomy 20p comprise a variable degree of developmental delay and mild to moderate intellectual disability, poor motor coordination, marked speech delay with difficulties in the articulation of some sounds. Typical facial dysmorphisms include a round face with full cheeks, thick coarse and usually straight hair, laterally arched eyebrows, upward slanting palpebral fissures, flared nostrils, high arched palate, abnormal teeth, occipital flattening and large misshapen ears. Other common features include variable skeletal anomalies including vertebral malformations (fusion of vertebrae, reduction of intervertebral spaces, spina bifida, scoliosis and kyphosis), hip deformity, and malposition of fingers and toes. Osteoporosis/osteopenia is reported in a few patients. Congenital heart defects and non-specific kidney abnormalities are present in some patients. Birth weight and growth pattern are usually normal. Less frequent physical abnormalities include umbilical and/or inguinal hernias and hypospadias. The extent and severity of clinical manifestations described above is contingent on the size and location of the duplication in 20p.
## Etiology
Trisomy 20p is a chromosomal abnormality resulting from duplication of a fraction of the short arm of chromosome 20, variable in length, with no recurrent breakpoints. It may occur de novo, but most reported cases arise from a reciprocal translocation or, as described in a few cases, a parental inversion. Trisomy 20p is therefore frequently associated with another chromosomal imbalance that may modify the clinical picture. Pure trisomy 20p resulting from isochromosome formation and whole arm translocation has been reported. Precise genotype-phenotype correlations remain elusive due to the small number of patients and heterogeneity of breakpoints.
## Diagnostic methods
Diagnosis is based on clinical manifestations leading to chromosomal analysis. Depending on their size, partial 20p duplications may be diagnosed by classical or molecular karyotyping. Molecular techniques are necessary for the genetic characterization of the duplication (FISH, MLPA, CGH array).
## Antenatal diagnosis
Prenatal diagnosis of 20p duplication is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Molecular techniques may be required depending on the size of the duplication.
## Genetic counseling
Genetic counseling is recommended and requires parental karyotyping to evaluate their risk of having another affected child.
## Management and treatment
Management is multi-disciplinary and requires evaluation and treatment by a pediatrician, and appropriate specialists. Patients will benefit from an early assessment and intervention with physiotherapy and occupational therapy.
## Prognosis
The prognosis is variable, depending on the size and location of the duplication and on the quality and timing of treatment. Exact life expectancy is unknown, and depends on whether severe congenital anomalies are present. The majority of individuals with trisomy 20p will live into adulthood.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Trisomy 20p
|
c2930888
| 7,571 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261318
| 2021-01-23T17:45:41 |
{"gard": ["5333"], "mesh": ["C535371"], "umls": ["C0265480", "C2930888"], "icd-10": ["Q92.2"], "synonyms": ["Dup(20p)", "Duplication of 20p", "Partial duplication of chromosome 20p", "Partial duplication of the short arm of chromosome 20", "Partial trisomy of chromosome 20p", "Partial trisomy of the short arm of chromosome 20"]}
|
Webbed penis
Other namesPenis palmatus, penoscrotal fusion
SpecialtyUrology
Webbed penis also known as buried or concealed penis is an acquired or congenital condition in which the scrotal skin extends onto the ventral penile shaft. The penile shaft is buried in scrotum or tethered to the scrotal midline by a fold or web of skin. The urethra and erectile bodies are usually normal. Webbed penis is usually asymptomatic, but the cosmetic appearance is often unacceptable. This condition may be corrected by surgical techniques.[1][2][3][4]
In the congenital form, the deformity represents an abnormality of the attachment between the penis and the scrotum; the penis, the urethra, and the remainder of the scrotum typically are normal.
Webbed penis may also be acquired (iatrogenic) after circumcision or other penile surgery, resulting from excessive removal of ventral penile skin; the penis can retract into the scrotum, resulting in secondary phimosis (trapped penis).
## Contents
* 1 Signs and Symptoms
* 2 Cause
* 3 Mechanism/Pathophysiology
* 4 Diagnosis
* 5 Prevention/Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 Research Directions
* 9 See also
* 10 References
## Signs and Symptoms[edit]
Since the penis does not protrude when a man has this disorder, his ability to pass urine when he is standing or to participate in sexual intercourse will be impaired.
Visible signs may include but are not limited to:
* Excessive skin and fat around the penis.
* Tight, scarred preputial orifice.
* Straining to urinate.[5]
## Cause[edit]
Webbed penis can be caused by various of things such as:
* Morbid obesity: which is known as excess fat around the genital area and abdomen, which makes the penis to appear as though it is hidden.
* Abnormalities that are there during birth - ligaments that attach the penis to underlying structures may be weaker than it is supposed to be.
* Lymphedema: this is when swelling occurs around the scrotum area due to collection of lymph fluid, which may cause the penis to be buried inside tissue.
## Mechanism/Pathophysiology[edit]
Concealed penis is due to a lack of skin or an inelasticity of the penile skin and a weak penile skin fixation or excessive suprapubic fat, the penile webbed is characterized by a ventral fold of skin which connects the distal shaft and a penoscrotum, and a penis which is tucked away with the scar tissue that exists.
Concealed penis is an unusual circumcision complication. The excision of excess preputial skin occurs, although inadequate internal preputial epithelium is cut out. The new preputial orifice is thus distal to the gland and pushes the penile shaft into the supra-pubic fat at the level of mons pubis. In these cases, the released shaft includes a skin graft or local flaps. The other probability of this mechanism is that, since the penis continues to shrink into the mons pubis, the healed scarred pre-utile opening gradually becomes subcutaneously stuck. In such cases, the released shaft needs no skin graft or local flaps, as we do. For both mechanisms, the preputial skin is inadequately excised, causing the preputial holes to be distal from the pulse, trapping the pulp when the procedure is complete.[6]
In relation to lymphedema - When the lymph system operates normally, the lymph circulates through a series of vessels and ducts throughout the body. It then returns to the bloodstream with lymph. A blocking or failure in the genital area of this system may lead to a lymphatic leak into the soft tissues surrounding the system.
In relation to obesity - Obesity is a general cause of adult acquired buried penis. There are some parallels with buried penis seen in infants, frequently associated with poor skin suspension, abnormal excess fat accumulation in the pubic region, penis webbing, or penis trapping due to scarring post-circumcision. Similarly, adult buried penis is often associated with a laxity of connective tissue between the dart fascia and the penis, allowing the penis to tunnel more closely through the pre-pubic skin due to "hypermobility." This is exacerbated by obesity and weight gain as the phallus is covered by the suprapubic fat pad.[7]
## Diagnosis[edit]
Typically a physical examination may be used to diagnose a person with a buried penis. A doctor should be able to differentiate between buried penis and a tiny penis, known as micropenis.[8]
## Prevention/Treatment[edit]
Adults with a buried penis either deal with or are subject to weight loss services. Weight loss programs are however sluggish and frequently do not "unbury" the penis; in addition, bad urine hygiene can lead to soft tissue infection.
While the condition can resolve without intervention in young children, if infection is present, patients may ultimately need a definite reconstruction and urgent procedure. Surgeons who treat this disorder are either urologic or plastic surgeons.[9]
Operational options can include ligament separation between penis base and pubic bone; skin graft output to cover penis areas requiring additional skin; liposuction using catheters to suck out fat cells from the region around the penis from below the skin; abdominoplasty that removes excess skin and fat from the area; an escutheonectomy to remove a fat pad just above the pubic area; or a panniculectomy in which pannicles are extracted, excess tissues and skin that hangs on the genitals and thighs.[10]
A form of prevention for this condition could be avoiding getting a circumcision in order to avoid complications along the line. On the other hand, proper circumcision is a key factor in preventing this complication of circumcision.[11] This condition requires the liberation of the concealed penis by carefully widening the close preputial hole and optimizing the circumcision, depending upon the etiology and formation process, with or without skin reconstruction.
* Doing skin grafts to cover areas of the penis where skin covering is needed; this may be required if circumcision removes too much skin.
* Suction lipectomy, which uses catheters to suck out fat cells from the area around the penis under the skin.
* Detachment of the ligaments that connect the base of the penis to the pubic bone.
* Panniculectomy that removes the pannus, excess fat and skin that hangs over the genitals and thighs.[12]
## Prognosis[edit]
A person with a concealed penis will have a normal life expectancy. In the studies that have been performed, it is shown that there are no current known side effects post-op. However, a patient might have a slight edema for about a month or two. The only side effect would be an operation scar.[13]
## Epidemiology[edit]
Webbed penis is considered to be a very uncommon condition, however it's prevalence is still unknown. Due to the fact that it occurs at birth, a high percentage of cases with condition are found in young children.[14]
## Research Directions[edit]
Webbed penis is when the penis is partially or completely concealed beneath the scrotum or when there is excess skin or fat around the pubic area. Various research is being conducted on this condition: for example, Webbed penis: A new classification[15] is a study that was conducted to suggest an operative method that can be planned based of the severity of the webbing condition. Other research has tried to test the introduction of a modified surgical procedure for repairing a concealed penis and compared the efficacy and feasibility of modified repair with traditional repair.[16]
An interesting research study was done between the years 2010 and 2014 to test a new surgical technique for concealed penis using an advanced musculocutaneous scrotal flap. The research showed that the advanced musculocutaneous scrotal flap technique for correcting concealed penis is technically easy and safe and the surgical method provided patients with a good cosmetic appearance, functional outcomes, and excellent postoperative satisfaction grades.[17]
## See also[edit]
* Buried penis
## References[edit]
1. ^ Abbate, B; Danti, DA; Pancani, S; Pampaloni, A (1994). "Congenital anomalies of the penis in children. A few consideration about 92 cases". Minerva Pediatr. 46 (4): 139–42. PMID 8084319.
2. ^ Bergeson, PS; Hopkin, RJ; Bailey Jr., RB; McGill, LC; Piatt, JP (1993). "The inconspicuous penis". Pediatrics. 92 (6): 794–9. PMID 8233739.
3. ^ Medina Lopez, RA; Campoy Martinez, P; Jimenez del Valle, U; Hernandez Soto, R; Ramirez Mendoza, A; Soltero Gonzalez, A (1999). "The webbed penis. A report of a new case". Arch Esp Urol. 52 (1): 68–9. PMID 10101890.
4. ^ Hara, M; Kanamori, S (1987). "A case of webbed penis". Hinyokika Kiyo. 33 (6): 951–2. PMID 3673843.
5. ^ Ho, Tammy S.; Gelman, Joel (August 2018). "Evaluation and management of adult acquired buried penis". Translational Andrology and Urology. 7 (4): 618–627. doi:10.21037/tau.2018.05.06. ISSN 2223-4691. PMC 6127540. PMID 30211051.
6. ^ Cimador, Marcello; Catalano, Pieralba; Ortolano, Rita; Giuffrè, Mario (April 2015). "The inconspicuous penis in children". Nature Reviews Urology. 12 (4): 205–215. doi:10.1038/nrurol.2015.49. ISSN 1759-4820. PMID 25850928. S2CID 38525398.
7. ^ Ho, Tammy S.; Gelman, Joel (August 2018). "Evaluation and management of adult acquired buried penis". Translational Andrology and Urology. 7 (4): 618–627. doi:10.21037/tau.2018.05.06. ISSN 2223-4691. PMC 6127540. PMID 30211051.
8. ^ "Concealed Penis | Ohio State Urology". wexnermedical.osu.edu. Retrieved 2020-11-12.
9. ^ (PDF). 2015-07-24 https://web.archive.org/web/20150724134835/http://www.hawaii.edu/hivandaids/Results_of_A_Simplified_Technique_for_Buried_Penis_Repair.pdf. Archived from the original (PDF) on 2015-07-24. Retrieved 2020-12-16. Missing or empty `|title=` (help)
10. ^ Elist, James J.; Baniqued, Matthew; Hosseini, Alireza; Wilson, Steven K. (May 2020). "Correction of retractile penis with subcutaneous soft silicone penile implant". International Journal of Impotence Research. 32 (3): 317–322. doi:10.1038/s41443-019-0174-3. ISSN 1476-5489. PMID 31383992. S2CID 199450704.
11. ^ Suliman, Mohamed taifour (2005). "Concealed penis in a 2-year-old boy: a rare complication of circumcision". Annals of Saudi Medicine. 25 (1): 56–57. doi:10.5144/0256-4947.2005.56. ISSN 0256-4947. PMC 6150566. PMID 15822497.
12. ^ Anandan, Lavanya; Mohammed, Aza (2018). "Surgical management of buried penis in adults". Central European Journal of Urology. 71 (3): 346–352. doi:10.5173/ceju.2018.1676. ISSN 2080-4806. PMC 6202613. PMID 30386659.
13. ^ Cheng, Gong; Liu, Bianjiang; Guan, Zhaolong; Huang, Yuan; Qin, Chao; Song, Ninghong; Wang, Zengjun (2015). "A modified surgical procedure for concealed penis". Canadian Urological Association Journal. 9 (9–10): E723–E726. doi:10.5489/cuaj.3028. ISSN 1911-6470. PMC 4662445. PMID 26664507.
14. ^ Jul 27, The Journal of Urology A. New Surgical Technique for the Treatment of Congenital Concealed Penis Based on Anatomical Finding J. Urol 2020; Zhang, H.; Zhao, G.; Feng, G.; Han, H.; Li, H.; Xiao, K.; Song, Y.; MEDLINE®/PubMed®, J. Cui From. "New Surgical Technique for the Treatment of Congenital Concealed Penis". PracticeUpdate. Retrieved 2020-12-16.
15. ^ El Gohary, Mohamed Amin; El-Koutby, Montasser (2010). "Webbed penis: A new classification". Journal of Indian Association of Pediatric Surgeons. 15 (2): 50–2. doi:10.4103/0971-9261.70637. ISSN 0971-9261. PMC 2952775. PMID 20975781.
16. ^ Chen, Yue-bing; Ding, Xian-fan; Luo, Chong; Yu, Shi-cheng; Yu, Yan-lan; Chen, Bi-de; Zhang, Zhi-gen; Li, Gong-hui (September 2012). "A new plastic surgical technique for adult congenital webbed penis". Journal of Zhejiang University. Science. B. 13 (9): 757–760. doi:10.1631/jzus.B1200117. ISSN 1673-1581. PMC 3437374. PMID 22949367.
17. ^ Han, Dong-Seok; Jang, Hoon; Youn, Chang-Shik; Yuk, Seung-Mo (2015-06-19). "A new surgical technique for concealed penis using an advanced musculocutaneous scrotal flap". BMC Urology. 15 (1): 54. doi:10.1186/s12894-015-0044-3. ISSN 1471-2490. PMC 4471909. PMID 26088081.
* v
* t
* e
Male congenital anomalies of the genitalia, including Intersex and DSD
Internal
Testicle
* Cryptorchidism
* Polyorchidism
* Monorchism
* Anorchia
* Sertoli cell-only syndrome
* True hermaphroditism
* Mixed gonadal dysgenesis
* Swyer syndrome
Vas deferens
* Congenital absence of the vas deferens
Other
* Persistent Müllerian duct syndrome
External
Penis
* Hypospadias
* Epispadias
* Chordee
* Micropenis
* Penile agenesis
* Diphallia
* Penoscrotal transposition
Other
* Pseudohermaphroditism
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Webbed penis
|
c0431670
| 7,572 |
wikipedia
|
https://en.wikipedia.org/wiki/Webbed_penis
| 2021-01-18T19:01:20 |
{"umls": ["C0431670"], "wikidata": ["Q14594748"]}
|
A laryngeal cleft or laryngotracheoesophageal cleft is a rare congenital abnormality in the posterior laryngo-tracheal wall.[1] It occurs in approximately 1 in 10,000 to 20,000 births.[2] It means there is a communication between the oesophagus and the trachea, which allows food or fluid to pass into the airway.[3]
## Contents
* 1 Presentation
* 1.1 Associated conditions
* 2 Diagnosis
* 3 Treatment
* 4 References
## Presentation[edit]
### Associated conditions[edit]
Twenty to 27% of individuals with a laryngeal cleft also have a tracheoesophageal fistula and approximately 6% of individuals with a fistula also have a cleft.[4] Other congenital anomalies commonly associated with laryngeal cleft are gastro-oesophageal reflux, tracheobronchomalacia, congenital heart defect, dextrocardia and situs inversus.[5] Laryngeal cleft can also be a component of other genetic syndromes, including Pallister-Hall syndrome and G syndrome (Opitz-Frias syndrome).[4]
## Diagnosis[edit]
Laryngeal cleft is usually diagnosed in an infant after they develop problems with feeding, such as coughing, cyanosis (blue lips) and failing to gain weight over time.[3] Pulmonary infections are also common.[4] The longer the cleft, the more severe are the symptoms. Laryngeal cleft is suspected after a video swallow study (VSS) shows material flowing into the airway rather than the esophagus, and diagnosis is confirmed through endoscopic examination, specifically microlaryngoscopy and bronchoscopy.[4][5] If a laryngeal cleft is not seen on flexible nasopharyngoscopy, that does not mean that there is not one there. Laryngeal clefts are classified into four types according to Benjamin and Inglis. Type I clefts extend down to the vocal cords; Type II clefts extend below the vocal cords and into the cricoid cartilage; Type III clefts extend into the cervical trachea and Type IV clefts extend into the thoracic trachea.[5] Subclassification of type IV clefts into Type IVA (extension to 5 mm below the innominate artery) and Type IV B (extension greater than 5 mm below the innominate artery) may help with preoperative selection of those who can be repaired via transtracheal approach (Type IV A) versus a cricotracheal separation approach (type IV B).[6][7]
## Treatment[edit]
Treatment of a laryngeal cleft depends on the length and resulting severity of symptoms. A shallow cleft (Type I) may not require surgical intervention.[5] Symptoms may be able to be managed by thickening the infant's feeds.[5] If symptomatic, Type I clefts can be sutured closed or injected with filler as a temporary fix to determine if obliterating the cleft is beneficial and whether or not a more formal closure is required at a later date.[8] Slightly longer clefts (Type II and short Type III) can be repaired endoscopically. Short type IV clefts extending to within 5 mm below the innominate artery can be repaired through the neck by splitting the trachea vertically in the midline and suturing the back layers of the esophagus and trachea closed.[6] A long, tapered piece of rib graft can be placed between the esophageal and tracheal layers to make them rigid so the patient will not require a tracheotomy after the surgery and to decrease chances of fistula postoperatively.[6] Long Type IV clefts extending further than 5 mm below the innominate artery cannot be reached with a vertical incision in the trachea, and therefore are best repaired through cricotracheal resection.[7] This involves separating the trachea from the cricoid cartilage, leaving the patient intubated through the trachea, suturing each of the esophagus and the back wall of the trachea closed independently, and then reattaching the trachea to the cricoid cartilage.[7] This prevents the need for pulmonary bypass or extracorporeal membrane oxygenation.[citation needed]
## References[edit]
1. ^ Thornton, M.; H. Rowley; B. J. Conlon; J. D. Russell (2001). "Type I laryngeal cleft: late presentation". The Journal of Laryngology & Otology. 115 (10): 821–822. doi:10.1258/0022215011909053. PMID 11667997.
2. ^ Pezzettigotta, S. M.; Leboulanger N.; Roger G.; Denoyelle F.; Garabédian E. N. (October 2008). "Laryngeal cleft". Otolaryngologic Clinics of North America. 41 (5): 913–33, ix. doi:10.1016/j.otc.2008.04.010. PMID 18775342.
3. ^ a b Cherry, John R. (1997). Ear Nose & Throat for Lawyers. Routledge. p. 368. ISBN 1-85941-210-6.
4. ^ a b c d Bluestone, Charles D. (2003). Pediatric otolaryngology, Volume 2. Elsevier Health Sciences. p. 1468. ISBN 0-7216-9197-8.
5. ^ a b c d e Graham, John M.; Glenis K. Scadding; Peter D. Bull (2008). Pediatric ENT. Springer. p. 193. ISBN 978-3-540-69930-9.
6. ^ a b c Propst, Evan J. (2016-04-01). "Repair of short type IV laryngotracheoesophageal cleft using long, tapered, engaging graft without need for tracheotomy". The Laryngoscope. 126 (4): 1006–1008. doi:10.1002/lary.25472. ISSN 1531-4995. PMID 26153063.
7. ^ a b c Propst, Evan J.; Ida, Jonathan B.; Rutter, Michael J. (2013-03-01). "Repair of long type IV posterior laryngeal cleft through a cervical approach using cricotracheal separation". The Laryngoscope. 123 (3): 801–804. doi:10.1002/lary.23660. ISSN 1531-4995. PMID 23297095.
8. ^ Chiang, Tendy; McConnell, Brook; Ruiz, Amanda G.; DeBoer, Emily M.; Prager, Jeremy D. (2014-12-01). "Surgical management of type I and II laryngeal cleft in the pediatric population". International Journal of Pediatric Otorhinolaryngology. 78 (12): 2244–2249. doi:10.1016/j.ijporl.2014.10.023. ISSN 1872-8464. PMID 25465448.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Laryngeal cleft
|
c1840311
| 7,573 |
wikipedia
|
https://en.wikipedia.org/wiki/Laryngeal_cleft
| 2021-01-18T18:40:20 |
{"gard": ["3188"], "mesh": ["C537875"], "umls": ["C1840311"], "orphanet": ["2004"], "wikidata": ["Q6491956"]}
|
A number sign (#) is used with this entry because this form of nonspecific X-linked mental retardation is caused by mutation in the ARX gene (300382) on chromosome Xp21.
Description
ARX-related mental retardation is a form of nonsyndromic X-linked mental retardation. It is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to Partington syndrome (309510) (Kato et al., 2004; Wallerstein et al., 2008).
Clinical Features
Hamel et al. (1999) described a two 4-generation families (MRX43 and MRX52) segregating X-linked mental retardation. Affected members in family MRX43 had moderate to profound nonprogressive mental retardation recognized in early childhood. Only 1 patient was able to read and write. Characteristic features included obesity, large head, periorbital fullness, wide palpebral fissures, full lower lip, and normal behavior. Two brothers were treated for epilepsy, one only in adolescence and the other into adulthood. Affected members in family MRX52 had moderate to profound nonprogressive mental retardation noted in childhood. Only 1 patient was able to accomplish basic academic tasks. Behavior was unremarkable, and characteristic features included downslanting palpebral fissures, and midface hypoplasia.
Laperuta et al. (2007) reported an Italian family in which 5 men had X-linked mental retardation (MRX87). There was marked intrafamilial variation with cognitive deficits ranging from moderate to severe. There were no dysmorphic features, but 3 patients had flat feet, 2 had urinary incontinence, and 1 had a congenital hindbrain herniation of the cerebellar tonsils. The oldest patient, age 67 years, had other neurologic signs, including pyramidal hypotonia, extensor plantar responses, hypoacusis, and signs of dementia. Genetic analysis identified a 24-bp duplication in the ARX gene (300382.0002). Carrier women were unaffected.
Mapping
In a family in which 7 males had X-linked mental retardation, Hane et al. (1996) found linkage to a locus, termed MRX29, on Xp22.3-p21.3. A maximal 2-point lod score of 3.31 was demonstrated for tight linkage to marker DXS1202 with crossovers between the 3-prime portion of the DMD (300377) gene (DXS1234) proximally and locus DXS989 distally. The localization of MRX29 overlapped with at least 6 other MRX entities linked to the distal short arm of the X chromosome, such as Partington syndrome and Coffin-Lowry syndrome (303600).
Hamel et al. (1999) performed linkage analysis in the MRX43 family and obtained a maximum lod score of 2.23 (theta = 0.0) with marker DXS985. Using haplotype construction, they identified DXS987 and DMD as the closest flanking markers, defining the region of linkage to Xp22.31-p21.2, spanning approximately 25 cM. Hamel et al. (1999) also performed linkage analysis in family MRX52 and obtained a maximum lod score of 3.14 (theta = 0.0) with marker DXS559. Using haplotype construction, they identified ALAS2 and DXS3 as the closest flanking markers, defining the region of linkage to Xp11.21-q22.3, spanning approximately 19 cM.
Jemaa et al. (1999) reported a large Tunisian family with X-linked nonspecific mental retardation. By linkage analysis, they identified a disease locus, termed MRX54, located in a critical region spanning approximately 2.7 cM between DXS989 and DXS1218 in Xp22.1-p21.3, with a maximum lod score of 3.56.
Molecular Genetics
In the MRX43 family reported by Hamel et al. (1999) and in the MRX76 family reported by Kleefstra et al. (2002), Bienvenu et al. (2002) identified the same 24-bp in-frame duplication (300382.0002) in the ARX gene.
In the MRX54 family reported by Jemaa et al. (1999), Bienvenu et al. (2002) identified a missense mutation in the ARX gene (300382.0013).
Stepp et al. (2005) identified the 24-bp duplication in the ARX gene in affected individuals from 4 of 11 unrelated families with X-linked mental retardation. The MRX29, MRX32, MRX33, and MRX38 families had previously been reported by Hane et al. (1996), Hane et al. (1999), Holinski-Feder et al. (1996), and Schutz et al. (1996), respectively. The findings suggested that the 24-bp duplication is the most common mutation in nonsyndromic XLMR families linked to Xp22.1.
De Brouwer (2019) stated that a missense mutation (R2085H; 300382.0025) in the ARX gene was identified in affected members of the MRX52 family reported by Hamel et al. (1999).
INHERITANCE \- X-linked recessive HEAD & NECK Eyes \- Periorbital fullness (in some patients) \- Wide palpebral fissures (in some patients) NEUROLOGIC Central Nervous System \- Mental retardation, mild to severe (IQ 21-67 for those reported) \- Seizures (in some patients) MOLECULAR BASIS \- Caused by mutation in the aristaless-related homeobox, X-linked gene (ARX, 300382.0002 ) ▲ 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
|
MENTAL RETARDATION, X-LINKED, WITH OR WITHOUT SEIZURES, ARX-RELATED
|
c2931498
| 7,574 |
omim
|
https://www.omim.org/entry/300419
| 2019-09-22T16:20:22 |
{"mesh": ["C567906"], "omim": ["300419"], "orphanet": ["777"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED 29", "MENTAL RETARDATION, X-LINKED 32", "MENTAL RETARDATION, X-LINKED 33", "MENTAL RETARDATION, X-LINKED 38", "MENTAL RETARDATION, X-LINKED 43", "MENTAL RETARDATION, X-LINKED 52", "MENTAL RETARDATION, X-LINKED 54", "MENTAL RETARDATION, X-LINKED 76", "MENTAL RETARDATION, X-LINKED 87"]}
|
A rare, genetic, chronic, recurrent, slowly progressive, epidermal disease characterized by small, sterile, pustular eruptions, involving the nails and surrounding skin of the fingers and/or toes, which coalesce and burst, leaving erythematous, atrophic skin where new pustules develop. Onychodystrophy is frequently associated and anonychia and osteolysis are reported in severe cases. Local expansion (to involve the hands, forearms and/or feet) and involvement of mucosal surfaces (e.g. conjunctiva, tongue, urethra) may be observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Acrodermatitis continua of Hallopeau
|
c0392439
| 7,575 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163931
| 2021-01-23T18:45:58 |
{"icd-10": ["L40.2"]}
|
Rivera et al. (1988) reported an apparently 'new' form of thoracomelic dysplasia in 2 children, a brother and sister of consanguineous parents. The salient features were bell-shaped thorax owing to short ribs, short-limbed dwarfism, pelvic hypoplasia, dislocatable radial heads, elongated distal fibulas, and improvement with age. Distinguishing the disorder from Jeune syndrome (208500) were the different thoracic configuration, lack of neonatal respiratory distress, and absence of acetabular spurs in infancy and of phalangeal cone-shaped epiphyses in childhood.
Limbs \- Dislocatable radial heads \- Elongated distal fibulas Inheritance \- Autosomal recessive Misc \- Improvement with age Skel \- Thoracomelic dysplasia \- Pelvic hypoplasia Growth \- Short-limbed dwarfism Thorax \- Bell-shaped thorax \- Short ribs ▲ 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
|
THORACOMELIC DYSPLASIA
|
c2931227
| 7,576 |
omim
|
https://www.omim.org/entry/273740
| 2019-09-22T16:21:45 |
{"mesh": ["C536516"], "omim": ["273740"], "orphanet": ["1803"], "synonyms": ["Alternative titles", "'THORACO-LIMB' DYSPLASIA"]}
|
CYLD cutaneous syndrome is a genetic condition characterized by the growth of multiple noncancerous (benign) skin tumors. These tumors develop from structures associated with the skin (skin appendages), such as hair follicles. More than one type of skin tumor often develops, including benign growths called cylindromas, spiradenomas, and trichoepitheliomas. Cylindromas were previously thought to derive from sweat glands, but they are now generally believed to begin in hair follicles and often appear on the scalp. Spiradenomas are related to cylindromas and it is common to find features of both of these benign growths in a single tumor. Trichoepitheliomas arise from hair follicles and typically develop on the skin around the nose and upper lip.
While the skin tumors associated with CYLD cutaneous syndrome are typically benign, occasionally they may become cancerous (malignant). When becoming malignant, tumors often grow rapidly and become open sores (ulcers). Affected individuals are also at increased risk of developing tumors in structures other than skin; for example benign or malignant tumors of the salivary glands occur in some people with the condition.
People with CYLD cutaneous syndrome typically begin developing tumors in late childhood or in their teens. For reasons that are unclear, females with CYLD cutaneous syndrome tend to develop more tumors than males with this condition. Tumors tend to grow larger and increase in number over time. Large benign tumors may become ulcers and prone to infections. The tumors are most often found on the head and neck, including the scalp. Tumors that occur in the eyes, ears, nose, or mouth can affect the senses, including vision and hearing. Less frequently, tumors develop on the torso, armpits, or genitals. Genital tumors may cause pain and sexual dysfunction. Rarely, cylindromas develop in the airways and can cause problems with breathing (respiratory insufficiency).
The tumors in CYLD cutaneous syndrome can be disfiguring and may contribute to depression or other psychological problems.
CYLD cutaneous syndrome includes the conditions previously called Brooke-Spiegler syndrome, multiple familial trichoepithelioma, and familial cylindromatosis. These conditions were once thought to be distinct disorders but are now considered to be the same condition.
## Frequency
The prevalence of CYLD cutaneous syndrome is unknown, but the condition is estimated to affect more than 1 in 100,000 individuals. More than 100 affected families have been reported in the scientific literature.
## Causes
CYLD cutaneous syndrome is caused by mutations in the CYLD gene. The CYLD gene provides instructions for making an enzyme that helps regulate numerous signaling pathways, many of which are involved in cell growth. By regulating these signaling pathways, the CYLD enzyme helps cells respond properly to signals that promote cell growth and division (proliferation) or self-destruction (apoptosis), as necessary. The CYLD enzyme acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way
People with CYLD cutaneous syndrome are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD enzyme from the altered copy of the gene. However, enough enzyme is usually produced from the remaining, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation that alters or removes (deletes) the normal copy of the CYLD gene must occur. The second mutation, called a somatic mutation, occurs during a person's lifetime and is found in only certain cells in the body.
When both copies of the CYLD gene are mutated, the cell cannot produce any functional CYLD enzyme. The loss of this enzyme allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with CYLD cutaneous syndrome, a second CYLD gene mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD enzyme in different types of cells, especially those in structures in the skin, leads to the growth of a variety of tumors.
### Learn more about the gene associated with CYLD cutaneous syndrome
* CYLD
## Inheritance Pattern
Susceptibility to CYLD cutaneous syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered CYLD gene in each of the body’s cells increases the risk of developing this condition. The initial genetic change is known as a germline mutation, which most individuals with this condition inherit from a parent. A second, somatic mutation is required for development of tumors in CYLD cutaneous syndrome. Depending when the second mutation occurs, the benign tumors may be clustered to one side of the body or face.
Rarely, the first CYLD gene mutation is not inherited but is a somatic mutation that occurs early in development. As a result, some of the body's cells have a normal version of the gene, while others have the mutated version. This situation is called mosaicism. As in inherited cases, a second somatic mutation in the normal copy of the gene later in life is required for tumors to develop. These cases of CYLD cutaneous syndrome are not inherited and typically occur in people with no history of the disorder in their family.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CYLD cutaneous syndrome
|
c1857941
| 7,577 |
medlineplus
|
https://medlineplus.gov/genetics/condition/cyld-cutaneous-syndrome/
| 2021-01-27T08:25:00 |
{"gard": ["10179", "9707", "10867"], "mesh": ["C536611"], "omim": ["605041", "132700", "601606"], "synonyms": []}
|
Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability before a seizure episode. In rare instances, children with this condition do not have seizures until they are 1 to 3 years old.
Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxine-dependent epilepsy. Instead, people with this type of seizure are medically treated with large daily doses of pyridoxine (a type of vitamin B6 found in food). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy). Even though seizures can be controlled with pyridoxine, neurological problems such as developmental delay and learning disorders may still occur.
## Frequency
Pyridoxine-dependent epilepsy occurs in 1 in 100,000 to 700,000 individuals. At least 100 cases have been reported worldwide.
## Causes
Mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy. The ALDH7A1 gene provides instructions for making an enzyme called α-aminoadipic semialdehyde (α-AASA) dehydrogenase, also known as antiquitin. This enzyme is involved in the breakdown of the protein building block (amino acid) lysine in the brain.
When antiquitin is deficient, a molecule that interferes with vitamin B6 function builds up in various tissues. Pyridoxine plays a role in many processes in the body, such as the breakdown of amino acids and the productions of chemicals that transmit signals in the brain (neurotransmitters). It is unclear how a lack of pyridoxine causes the seizures that are characteristic of this condition.
Some individuals with pyridoxine-dependent epilepsy do not have identified mutations in the ALDH7A1 gene. In these cases, the cause of the condition is unknown.
### Learn more about the gene associated with Pyridoxine-dependent epilepsy
* ALDH7A1
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pyridoxine-dependent epilepsy
|
c1849508
| 7,578 |
medlineplus
|
https://medlineplus.gov/genetics/condition/pyridoxine-dependent-epilepsy/
| 2021-01-27T08:25:47 |
{"gard": ["9298"], "mesh": ["C536254"], "omim": ["266100"], "synonyms": []}
|
A rare partial autosomal trisomy/tetrasomy characterized by facial dysmorphism (long thin face, prominent forehead, down-slanting palpebral fissures, prominent nose with broad nasal bridge, prominent chin), pre- and postnatal overgrowth, renal anomalies (e.g. horseshoe kidney, renal agenesis, hydronephrosis), mild to severe learning difficulties and behavioral abnormalities. Additional features may include craniosynostosis and macrocephaly.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
15q overgrowth syndrome
|
c3553858
| 7,579 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314585
| 2021-01-23T19:10:21 |
{"omim": ["614846"], "icd-10": ["Q87.3"]}
|
A number sign (#) is used with this entry because a subset of renal cell carcinomas (RCC) harbor translocations involving chromosome Xp11 with breakpoints impacting the TFE3 transcription factor gene (314310).
Description
Xp11 translocation renal cell carcinomas (RCCX1) are a group of neoplasms distinguished by chromosomal translocations with breakpoints involving the TFE3 gene within tumor cells. The result is a TFE3 transcription factor gene fusion with 1 of multiple reported genes including ASPRCR1 (606236) on chromosome 17q25 and PRCC (179755) on 1q21, and more rarely, NONO (300084) on Xq13, SFPQ (605199) on 1p34, CLTC (118955) on 17q23, and unknown genes on chromosomes 3 and 10. Xp11 translocations are often found in pediatric tumors and less commonly in adults. However, adult cases may outnumber pediatric cases since renal cell carcinoma is more common in the adult population. Prior chemotherapy is a known risk factor for Xp11 translocations. Histology shows both clear cells and papillary architecture, often with abundant psammoma bodies, although variable histologic features have been observed (review by Ross and Argani, 2010).
For a discussion of genetic heterogeneity of renal cell carcinoma, see RCC (144700).
Clinical Features
Perot et al. (2003) reported 5 cases of juvenile renal cell carcinoma with translocations involving Xp11.2. Tumor tissue from a 12-year-old boy and a 14-year-old girl both had a t(X;1)(p11.2;q21) translocation, tumor tissue from a 9-year-old boy and a 31-year-old woman both had a t(X;1)(p11.2;p34) translocation, and tumor tissue from a 15-year-old boy had a t(X;17)(p11.2;q25) translocation. Histologic studies showed that 2 were likely papillary RCC, with clear or slightly eosinophilic cells, and 2 were a clear cell RCC, whereas 1 showed a mixture of papillary and clear cell RCC architecture. Perot et al. (2003) concluded that RCC with translocations involving Xp11.2 forms a specific entity with a young age of occurrence.
Cytogenetics
### ASPSCR1/TFE3 Fusion Gene
In papillary renal cell carcinoma tissue from two 5-year-old Belgian girls of African origin, Heimann et al. (2001) identified a translocation t(X;17)(p11.2;q25) that fused the N-terminal region of the ASPSPR1 gene to the C-terminal region of TFE3 including the bHLH DNA-binding domain and the leucine zipper dimerization domain. The same fusion gene had been identified in cases of alveolar soft part sarcoma (ASPS; 606243) (Joyama et al., 1999).
### PRCC/TFE3 Fusion Gene
Sidhar et al. (1996) demonstrated that the specific chromosomal translocation t(X;1)(p11.2;q21.2) observed in 3 papillary renal carcinomas results in the fusion of a gene at 1q21.2, designated PRCC, to the TFE3 gene at Xp11.2. Weterman et al. (1996) also identified these 2 genes involved in the t(X;1)(p11;q21) translocation in human papillary renal cell carcinomas.
### CLTC/TFE3 Fusion Gene
Argani et al. (2003) reported a case of renal cell carcinoma in which the 5-prime exons of the CLTC gene were fused with the 3-prime exons of the TFE3 gene as a result of a translocation, t(X;17)(p11.2;q23). The patient was a 14-year-old boy who presented with gross hematuria and was found by CT to have a finely calcified left renal mass.
### SFPQ/TFE3 Fusion Gene
Clark et al. (1997) identified cases of papillary renal cell carcinoma in which the splicing factor gene PSF was partnered with the TFE3 gene as a result of a translocation, t(X;1)(p11.2;p34).
### NONO/TFE3 Fusion Gene
In papillary renal cell carcinoma tissue, Clark et al. (1997) identified an X-chromosome inversion inv(X)(p11.2;q12) that resulted in the fusion of the NONO gene to TFE3.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
RENAL CELL CARCINOMA, Xp11-ASSOCIATED
|
c3275446
| 7,580 |
omim
|
https://www.omim.org/entry/300854
| 2019-09-22T16:19:28 |
{"doid": ["4450"], "omim": ["300854"], "orphanet": ["319308"], "synonyms": ["Carcinoma associated with MITF/TFE translocation", "Translocation renal cell carcinoma"]}
|
Neonatal scleroderma is a very rare, secondary, neonatal autoimmune disease characterized by neonatal-onset of erythematous skin lesions with a linear appearance that gradually become indurated and hyperpigmented and progressively present skin atrophy. Positive serum antibodies (in particular antinuclear antibodies and/or rheumatoid factor) may be associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Neonatal scleroderma
|
c4509425
| 7,581 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398127
| 2021-01-23T18:18:27 |
{"icd-10": ["P83.8"]}
|
Vertebral artery dissection
Other namesVertebral dissection
Arteries of the neck, with arrows indicating the right vertebral artery
SpecialtyCardiology
SymptomsHeadache, difficulty speaking, difficulty swallowing, poor coordination
ComplicationsStroke, subarachnoid hemorrhage
CausesTrauma, Ehler's Danlos syndrome, Marfan syndrome
Diagnostic methodComputed tomography angiography, magnetic resonance angiography, invasive angiography
TreatmentAnticoagulation, angioplasty, surgery
MedicationAspirin, heparin, warfarin
Frequency1.1 per 100,000
Vertebral artery dissection (VAD) is a flap-like tear of the inner lining of the vertebral artery, which is located in the neck and supplies blood to the brain. After the tear, blood enters the arterial wall and forms a blood clot, thickening the artery wall and often impeding blood flow. The symptoms of vertebral artery dissection include head and neck pain and intermittent or permanent stroke symptoms such as difficulty speaking, impaired coordination and visual loss. It is usually diagnosed with a contrast-enhanced CT or MRI scan.[1][2]
Vertebral dissection may occur after physical trauma to the neck, such as a blunt injury (e.g. traffic collision), or strangulation, or after sudden neck movements, i.e. coughing, but may also happen spontaneously. 1–4% of spontaneous cases have a clear underlying connective tissue disorder affecting the blood vessels. Treatment is usually with either antiplatelet drugs such as aspirin or with anticoagulants such as heparin or warfarin.[1]
Vertebral artery dissection is less common than carotid artery dissection (dissection of the large arteries in the front of the neck). The two conditions together account for 10–25% of non-hemorrhagic strokes in young and middle-aged people. Over 75% recover completely or with minimal impact on functioning, with the remainder having more severe disability and a very small proportion (about 2%) dying from complications.[1][3] It was first described in the 1970s by the Canadian neurologist C. Miller Fisher.[3]
## Contents
* 1 Classification
* 2 Signs and symptoms
* 3 Causes
* 3.1 Spontaneous
* 3.2 Traumatic
* 4 Mechanism
* 5 Diagnosis
* 6 Treatment
* 6.1 Anticoagulation and aspirin
* 6.2 Thrombolysis, stenting and surgery
* 7 Prognosis
* 8 Epidemiology
* 9 History
* 10 Notable cases
* 11 References
* 12 External links
* 13 See also
## Classification[edit]
Vertebral artery dissection is one of the two types of dissection of the arteries in the neck. The other type, carotid artery dissection, involves the carotid arteries. Vertebral artery dissection is further classified as being either traumatic (caused by mechanical trauma to the neck) or spontaneous, and it may also be classified by the part of the artery involved: extracranial (the part outside the skull) and intracranial (the part inside the skull).[1]
## Signs and symptoms[edit]
Head pain occurs in 50–75% of all cases of vertebral artery dissection. It tends to be located at the back of the head, either on the affected side or in the middle, and develops gradually. It is either dull or pressure-like in character or throbbing. About half of those with VAD consider the headache distinct, while the remainder have had a similar headache before.[1] It is suspected that VAD with headache as the only symptom is fairly common;[2] 8% of all cases of vertebral and carotid dissection are diagnosed on the basis of pain alone.[1]
Obstruction of blood flow through the affected vessel may lead to dysfunction of part of the brain supplied by the artery. This happens in 77–96% of cases. This may be temporary ("transient ischemic attack") in 10–16% of cases, but many (67–85% of cases) end up with a permanent deficit or a stroke. The vertebral artery supplies the part of the brain that lies in the posterior fossa of the skull, and this type of stroke is therefore called a posterior circulation infarct. Problems may include difficulty speaking or swallowing (lateral medullary syndrome); this occurs in less than a fifth of cases and occurs due to dysfunction of the brainstem. Others may experience unsteadiness or lack of coordination due to involvement of the cerebellum, and still others may develop visual loss (on one side of the visual field) due to involvement of the visual cortex in the occipital lobe.[1] In the event of involvement of the sympathetic tracts in the brainstem, a partial Horner's syndrome may develop; this is the combination of a drooping eyelid, constricted pupil, and an apparently sunken eye on one side of the face.[1]
If the dissection of the artery extends to the part of the artery that lies inside the skull, subarachnoid hemorrhage may occur (1% of cases). This arises due to rupture of the artery and accumulation of blood in the subarachnoid space. It may be characterized by a different, usually severe headache; it may also cause a range of additional neurological symptoms.[1][2]
13–16% of all people with vertebral or carotid dissection have dissection in another cervical artery. It is therefore possible for the symptoms to occur on both sides, or for symptoms of carotid artery dissection to occur at the same time as those of vertebral artery dissection.[2] Some give a figure of multiple vessel dissection as high as 30%.[3]
## Causes[edit]
The causes of vertebral artery dissection can be grouped under two main categories, spontaneous and traumatic.
### Spontaneous[edit]
Spontaneous cases are considered to be caused by intrinsic factors that weaken the arterial wall.[1] Only a very small proportion (1–4%) have a clear underlying connective tissue disorder, such as Ehlers–Danlos syndrome type 4 and, more rarely, Marfan syndrome.[1][2] Ehlers–Danlos syndrome type 4, caused by mutations of the COL3A gene, leads to defective production of the collagen, type III, alpha 1 protein and causes skin fragility as well as weakness of the walls of arteries and internal organs.[4] Marfan syndrome results from mutations in the FBN1 gene, defective production of the protein fibrillin-1, and a number of physical abnormalities including aneurysm of the aortic root.[4]
There have also been reports in other genetic conditions, such as osteogenesis imperfecta type 1, autosomal dominant polycystic kidney disease and pseudoxanthoma elasticum,[1] α1 antitrypsin deficiency and hereditary hemochromatosis, but evidence for these associations is weaker.[2][5] Genetic studies in other connective tissue-related genes have mostly yielded negative results.[1] Other abnormalities to the blood vessels, such as fibromuscular dysplasia, have been reported in a proportion of cases.[1][2] Atherosclerosis does not appear to increase the risk.[1]
There have been numerous reports of associated risk factors for vertebral artery dissection; many of these reports suffer from methodological weaknesses, such as selection bias.[6] Elevated homocysteine levels, often due to mutations in the MTHFR gene, appear to increase the risk of vertebral artery dissection.[5][6] People with an aneurysm of the aortic root and people with a history of migraine may be predisposed to vertebral artery dissection.[6]
### Traumatic[edit]
Traumatic vertebral dissection may follow blunt trauma to the neck, such as in a traffic collision, direct blow to the neck, strangulation,[1] or whiplash injury.[7] 1–2% of those with major trauma may have an injury to the carotid or vertebral arteries.[2] In many cases of vertebral dissection, people report recent very mild trauma to the neck or sudden neck movements, e.g. in the context of playing sports. Others report a recent infection, particularly respiratory tract infections associated with coughing.[1] Trauma has been reported to have occurred within a month of dissection in 40% with nearly 90% of this time the trauma being minor.[8] It has been difficult to prove the association of vertebral artery dissection with mild trauma and infections statistically.[1] It is likely that many "spontaneous" cases may in fact have been caused by such relatively minor insults in someone predisposed by other structural problems to the vessels.[1]
Vertebral artery dissection has also been reported in association with some forms of neck manipulation.[9] There is significant controversy about the level of risk of stroke from neck manipulation.[9] It may be that manipulation can cause dissection,[10] or it may be that the dissection is already present in some people who seek manipulative treatment.[11] At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association.[9]
## Mechanism[edit]
A reconstruction of the vertebral arteries from a CT scan, seen from the front. From the bottom, V1 is from the subclavian artery to the foramina, V2 is from the foramina to the second vertebra, V3 is between the foramina until entry into the skull, and V4 is inside the skull embedded in the dura mater. They merge into the basilar artery, which then divides into the posterior cerebral artery.
The vertebral arteries arise from the subclavian artery, and run through the transverse foramen of the upper six vertebrae of the neck. After exiting at the level of the first cervical vertebra, its course changes from vertical to horizontal, and then enters the skull through the foramen magnum. Inside the skull, the arteries merge to form the basilar artery, which joins the circle of Willis. In total, three quarters of the artery are outside the skull; it has a high mobility in this area due to rotational movement in the neck and is therefore vulnerable to trauma. Most dissections happen at the level of the first and second vertebrae. The vertebral artery supplies a number of vital structures in the posterior cranial fossa, such as the brainstem, the cerebellum and the occipital lobes. The brainstem harbors a number of vital functions (such as respiration) and controls the nerves of the face and neck. The cerebellum is part of the diffuse system that coordinates movement. Finally, the occipital lobes participate in the sense of vision.[1]
Dissection occurs when blood accumulates in the wall of the blood vessel. This is most likely due to a tear in the tunica intima (the inner layer), allowing blood to enter the tunica media, although other lines of evidence have suggested that the blood may instead arise from the vasa vasorum, the small blood vessels that supply the outer layer of larger blood vessels.[1][2] Various theories exist as to whether people who sustain carotid and vertebral artery dissection, even if not suffering from a connective tissue disorder, have an underlying vulnerability. Biopsy samples of skin and other arteries has indicated that this might be a possibility, but no genetic defect in collagen or elastin genes has been convincingly proven. Other studies have indicated inflammation of the blood vessels, as measured by highly sensitive C-reactive protein (hsCRP, a marker of inflammation) in the blood.[1]
Once dissection has occurred, two mechanisms contribute to the development of stroke symptoms. Firstly, the flow through the blood vessel may be disrupted due to the accumulation of blood under the vessel wall, leading to ischemia (insufficient blood supply). Secondly, irregularities in the vessel wall and turbulence increase the risk of thrombosis (the formation of blood clots) and embolism (migration) of these clots of the brain. From various lines of evidence, it appears that thrombosis and embolism is the predominant problem.[1]
Subarachnoid hemorrhage due to arterial rupture typically occurs if the dissection extends into the V4 section of the artery. This may be explained by the fact that the arterial wall is thinner and lacks a number of structural supports in this section.[1][3][12]
## Diagnosis[edit]
Magnetic resonance angiogram of the neck vessels in a person with Ehlers-Danlos syndrome type IV; it shows a dissection of the left internal carotid artery, dissection of both vertebral arteries in their V1 and V2 segments and a dissection of the middle and distal third of the right subclavian artery. Such striking episodes of dissection are typical for this "vascular" subtype of Ehlers-Danlos syndrome.
Various diagnostic modalities exist to demonstrate blood flow or absence thereof in the vertebral arteries. The gold standard is cerebral angiography (with or without digital subtraction angiography).[3][13][14] This involves puncture of a large artery (usually the femoral artery) and advancing an intravascular catheter through the aorta towards the vertebral arteries. At that point, radiocontrast is injected and its downstream flow captured on fluoroscopy (continuous X-ray imaging).[15] The vessel may appear stenotic (narrowed, 41–75%), occluded (blocked, 18–49%), or as an aneurysm (area of dilation, 5–13%). The narrowing may be described as "rat's tail" or "string sign".[1] Cerebral angiography is an invasive procedure, and it requires large volumes of radiocontrast that can cause complications such as kidney damage.[15] Angiography also does not directly demonstrate the blood in the vessel wall, as opposed to more modern modalities.[1][2] The only remaining use of angiography is when endovascular treatment is contemplated (see below).[1]
More modern methods involve computed tomography (CT angiography) and magnetic resonance imaging (MR angiography). They use smaller amounts of contrast and are not invasive. CT angiography and MR angiography are more or less equivalent when used to diagnose or exclude vertebral artery dissection.[13] CTA has the advantage of showing certain abnormalities earlier, tends to be available outside office hours, and can be performed rapidly.[1] When MR angiography is used, the best results are achieved in the T1 setting[2] using a protocol known as "fat suppression".[1][2][3] Doppler ultrasound is less useful as it provides little information about the part of the artery close to the skull base and in the vertebral foramina, and any abnormality detected on ultrasound would still require confirmation with CT or MRI.[1][2][3]
## Treatment[edit]
Treatment is focused on reducing stroke episodes and damage from a distending artery.[3] Four treatment modalities have been reported in the treatment of vertebral artery dissection. The two main treatments involve medication: anticoagulation (using heparin and warfarin) and antiplatelet drugs (usually aspirin). More rarely, thrombolysis (medication that dissolves blood clots) may be administered, and occasionally obstruction may be treated with angioplasty and stenting. No randomized controlled trials have been performed to compare the different treatment modalities.[1][16] Surgery is only used in exceptional cases.[1]
### Anticoagulation and aspirin[edit]
Aspirin (tablets pictured) is commonly used after stroke. In vertebral artery dissection it appears as effective as anticoagulation with warfarin.
From analysis of the existing small treatment trials of cervical artery dissection (carotid and vertebral) it appears that aspirin and anticoagulation (heparin followed by warfarin) are equally effective in reducing the risk of further stroke or death. Anticoagulation is regarded as more powerful than antiplatelet therapy, but anticoagulants may increase the size of the hematoma and worsen obstruction of the affected artery.[16] Anticoagulation may be relatively unsafe if a large stroke has already occurred, as hemorrhagic transformation is relatively common, and if the dissection extends into V4 (carrying a risk of subarachnoid hemorrhage). Anticoagulation may be appropriate if there is rapid blood flow (through a severely narrowed vessel) on transcranial doppler despite the use of aspirin, if there is a completely occluded vessel, if there are recurrent stroke-like episodes, or if free-floating blood clot is visible on scans.[1][2][17] Warfarin is typically continued for 3–6 months, as during this time the flow through the artery usually improves, and most strokes happen within the first 6 months after the development of the dissection.[1] Some regard 3 months as sufficient.[3]
Professional guidelines in the UK recommend that patients with VA dissection should be enrolled in a clinical trial comparing aspirin and anticoagulation if possible.[18] American guidelines state that the benefit of anticoagulation is not currently established.[19]
### Thrombolysis, stenting and surgery[edit]
Thrombolysis, stenting and surgery are not used as widely as anticoagulation or antiplatelet drugs. These treatments are invasive, and are typically reserved for situations where symptoms worsen despite medical treatment, or where medical treatment may be unsafe (e.g. an unacceptable bleeding tendency).[1][2]
Thrombolysis is enzymatic destruction of blood clots. This is achieved by the administration of a drug (such as urokinase or alteplase) that activates plasmin, an enzyme that occurs naturally in the body and digests clots when activated. Thrombolysis is an accepted treatment for heart attacks and stroke unrelated to dissection. In cervical artery dissection, only small case series are available. The thrombolytic drug is administered either intravenously or during cerebral angiography through a catheter directly into the affected artery. The data indicates that thrombolysis is safe, but its place in the treatment of VAD is uncertain.[16]
Stenting involves the catheterization of the affected artery during angiography, and the insertion of a mesh-like tube; this is known as "endovascular therapy" (inside the blood vessel). This may be performed to allow the blood to flow through a severely narrowed vessel, or to seal off an aneurysm. However, it is unclear whether the technical success of the procedure translates into improved outcomes, as in both cases the problem often resolves spontaneously over time.[16] Stenting, as well as the insertion of coils by means of angiography, may be performed if there is an aneurysm and/or extension of the dissection into the V4 section of the artery.[12]
Surgery carries a high risk of complications, and is typically only offered in case of inexorable deterioration or contraindications to any of the other treatments. Various arterial repair procedures have been described.[1][12]
## Prognosis[edit]
Prognosis of spontaneous cervical arterial dissection involves neurological and arterial results. The overall functional prognosis of individuals with stroke due to cervical artery dissection does not appear to vary from that of young people with stroke due to other causes. The rate of survival with good outcome (a modified Rankin score of 0–2) is generally about 75%,[1][3] or possibly slightly better (85.7%) if antiplatelet drugs are used.[1] In studies of anticoagulants and aspirin, the combined mortality with either treatment is 1.8–2.1%.[1][16]
After the initial episode, 2% may experience a further episode within the first month. After this, there is a 1% annual risk of recurrence.[1] Those with high blood pressure and dissections in multiple arteries may have a higher risk of recurrence.[2] Further episodes of cervical artery dissection are more common in those who are younger, have a family history of cervical artery dissection, or have a diagnosis of Ehlers-Danlos syndrome or fibromuscular dysplasia.[2]
## Epidemiology[edit]
The annual incidence is about 1.1 per 100,000 annually in population studies from the United States and France. From 1994 to 2003, the incidence increased threefold; this has been attributed to the more widespread use of modern imaging modalities rather than a true increase.[1] Similarly, those living in urban areas are more likely to receive appropriate investigations, accounting for increased rates of diagnosis in those dwelling in cities. It is suspected that a proportion of cases in people with mild symptoms remains undiagnosed.[2]
There is controversy as to whether VAD is more common in men or in women; an aggregate of all studies shows that it is slightly higher incidence in men (56% versus 44%).[1] Men are on average 37–44 years old at diagnosis, and women 34–44. While dissection of the carotid and vertebral arteries accounts for only 2% of strokes (which are usually caused by high blood pressure and other risk factors, and tend to occur in the elderly), they cause 10–25% of strokes in young and middle-aged people.[1][3]
Dissecting aneurysms of the vertebral artery constitute 4% of all cerebral aneurysms, and are hence a relatively rare but important cause of subarachnoid hemorrhage.[12]
## History[edit]
Spontaneous vertebral artery dissection was described in the 1970s. Prior to this, there had been isolated case reports about carotid dissection. In 1971, C. Miller Fisher, a Canadian neurologist and stroke physician working at Massachusetts General Hospital, first noted the "string sign" abnormality in carotid arteries on cerebral angiograms of stroke patients, and subsequently discovered that the same abnormality could occur in the vertebral arteries. He reported the discovery in a paper in 1978.[3][20][21]
## Notable cases[edit]
Australian cricketer Phillip Hughes died on 27 November 2014 after developing a vertebral artery dissection as a result of being struck on the side of the neck by a cricket ball during a Sheffield Shield match on 25 November 2014. The ball struck Hughes on the base of the skull just behind his left ear which caused a vertebral artery dissection complicated by subarachnoid hemorrhage.[22]
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq Kim YK, Schulman S (April 2009). "Cervical artery dissection: pathology, epidemiology and management". Thromb. Res. 123 (6): 810–21. doi:10.1016/j.thromres.2009.01.013. PMID 19269682.
2. ^ a b c d e f g h i j k l m n o p q r Debette S, Leys D (July 2009). "Cervical-artery dissections: predisposing factors, diagnosis, and outcome". Lancet Neurol. 8 (7): 668–78. doi:10.1016/S1474-4422(09)70084-5. PMID 19539238.
3. ^ a b c d e f g h i j k l Campos-Herrera CR, Scaff M, Yamamoto FI, Conforto AB (December 2008). "Spontaneous cervical artery dissection: an update on clinical and diagnostic aspects". Arq Neuropsiquiatr. 66 (4): 922–7. doi:10.1590/S0004-282X2008000600036. PMID 19099146.
4. ^ a b Callewaert B, Malfait F, Loeys B, De Paepe A (March 2008). "Ehlers-Danlos syndromes and Marfan syndrome". Best Pract Res Clin Rheumatol. 22 (1): 165–89. doi:10.1016/j.berh.2007.12.005. PMID 18328988.
5. ^ a b Debette S, Markus HS (June 2009). "The genetics of cervical artery dissection: a systematic review". Stroke. 40 (6): e459–66. doi:10.1161/STROKEAHA.108.534669. PMID 19390073.
6. ^ a b c Rubinstein SM, Peerdeman SM, van Tulder MW, Riphagen I, Haldeman S (July 2005). "A systematic review of the risk factors for cervical artery dissection". Stroke. 36 (7): 1575–80. doi:10.1161/01.STR.0000169919.73219.30. PMID 15933263.
7. ^ Siegmund, GP; Winkelstein, BA; Ivancic, PC; Svensson, MY; Vasavada, A (April 2009). "The anatomy and biomechanics of acute and chronic whiplash injury". Traffic Injury Prevention. 10 (2): 101–12. doi:10.1080/15389580802593269. PMID 19333822.
8. ^ Debette, S (February 2014). "Pathophysiology and risk factors of cervical artery dissection: what have we learnt from large hospital-based cohorts?". Current Opinion in Neurology. 27 (1): 20–8. doi:10.1097/wco.0000000000000056. PMID 24300790.
9. ^ a b c Haynes MJ, Vincent K, Fischhoff C, Bremner AP, Lanlo O, Hankey GJ (2012). "Assessing the risk of stroke from neck manipulation: a systematic review". International Journal of Clinical Practice. 66 (10): 940–947. doi:10.1111/j.1742-1241.2012.03004.x. PMC 3506737. PMID 22994328.
10. ^ Ernst E (2010). "Vascular accidents after neck manipulation: cause or coincidence?". Int J Clin Pract. 64 (6): 673–7. doi:10.1111/j.1742-1241.2009.02237.x. PMID 20518945.
11. ^ Guzman J, Haldeman S, Carroll LJ, et al. (February 2009). "Clinical practice implications of the bone and joint decade 2000–2010 Task Force on Neck Pain and Its Associated Disorders: from concepts and findings to recommendations". J Manipulative Physiol Ther. 32 (2 Suppl): S227–43. doi:10.1016/j.jmpt.2008.11.023. PMID 19251069. "In persons younger than 45 years, there is an association between chiropractic care and vertebro-basilar artery (VBA) stroke; there is a similar association between family physician care and VBA stroke. This suggests that there is no increased risk of VBA stroke after chiropractic care, and that these associations are likely due to patients with headache and neck pain from vertebral artery dissection seeking care while in the prodromal stage of a VBA stroke. Unfortunately, there is no practical or proven method to screen patients with neck pain and headache for vertebral artery dissection. However, VBA strokes are extremely rare, especially in younger persons."
12. ^ a b c d Santos-Franco JA, Zenteno M, Lee A (April 2008). "Dissecting aneurysms of the vertebrobasilar system. A comprehensive review on natural history and treatment options". Neurosurg Rev. 31 (2): 131–40, discussion 140. doi:10.1007/s10143-008-0124-x. PMID 18309525.
13. ^ a b Provenzale JM, Sarikaya B (October 2009). "Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature". AJR Am J Roentgenol. 193 (4): 1167–74. doi:10.2214/AJR.08.1688. PMID 19770343.
14. ^ Latchaw RE, Alberts MJ, Lev MH, et al. (November 2009). "Recommendations for imaging of acute ischemic stroke: a scientific statement from the American Heart Association". Stroke. 40 (11): 3646–78. doi:10.1161/STROKEAHA.108.192616. PMID 19797189.
15. ^ a b Kaufmann TJ, Kallmes DF (June 2008). "Diagnostic cerebral angiography: archaic and complication-prone or here to stay for another 80 years?". AJR Am J Roentgenol. 190 (6): 1435–7. doi:10.2214/AJR.07.3522. PMID 18492888.
16. ^ a b c d e Menon R, Kerry S, Norris JW, Markus HS (October 2008). "Treatment of cervical artery dissection: a systematic review and meta-analysis". J. Neurol. Neurosurg. Psychiatry. 79 (10): 1122–7. doi:10.1136/jnnp.2007.138800. PMID 18303104.
17. ^ Engelter ST, Brandt T, Debette S, et al. (September 2007). "Antiplatelets versus anticoagulation in cervical artery dissection". Stroke. 38 (9): 2605–11. doi:10.1161/STROKEAHA.107.489666. PMID 17656656.
18. ^ National Institute for Health and Clinical Excellence. Clinical guideline 68: Stroke. London, 2008.
19. ^ Adams HP, del Zoppo G, Alberts MJ, et al. (May 2007). "Guidelines for the early management of adults with ischemic stroke". Stroke. 38 (5): 1655–711. doi:10.1161/STROKEAHA.107.181486. PMID 17431204.
20. ^ Fisher CM, Ojemann RG, Roberson GH (February 1978). "Spontaneous dissection of cervico-cerebral arteries". Can J Neurol Sci. 5 (1): 9–19. doi:10.1017/S0317167100024690. PMID 647502.
21. ^ Fisher CM (November 2001). "A career in cerebrovascular disease: a personal account". Stroke. 32 (11): 2719–24. doi:10.1161/hs1101.098765. PMID 11692045.
22. ^ Coverdale, Brydon (27 November 2014). "Hughes suffered extremely rare, freak injury to neck". ESPN. Retrieved 27 November 2014.
## External links[edit]
Classification
D
* ICD-10: I67.0
* ICD-9-CM: 443.24
* MeSH: D020217
* DiseasesDB: 13831
External resources
* MedlinePlus: 001423.
* eMedicine: emerg/832
* Cervical Artery Dissections and Ischemic Stroke Patients, international research collaboration into cervical artery dissection
* 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
## See also[edit]
* Aortic dissection
* Carotid artery dissection
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Vertebral artery dissection
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c0338586
| 7,582 |
wikipedia
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https://en.wikipedia.org/wiki/Vertebral_artery_dissection
| 2021-01-18T19:08:16 |
{"mesh": ["D020217"], "icd-9": ["443.24"], "icd-10": ["I67.0"], "wikidata": ["Q7922751"]}
|
A parasitic disease caused by tissue-invasive, vector-borne nematodes which can be found anywhere in the human body and that are transmitted to humans through the bite of an infected mosquito or fly or by consumption of unsafe drinking water and which, depending on the subtype can manifest with lymphedema, dermatitis, subcutaneous edema and eye involvement. The disorder is a major public health problem in many tropical and subtropical countries. Six subtypes have been described in the literature: lymphatic filariasis, onchocerciasis, loiasis, mansonelliasis, dirofilariasis and dracunculiasis caused by Wuchereria bancrofti and filarioidea of the genus Brugia; Onchocerca volvulus; Loa loa; Mansonella; Dirofilaria; and Dracunculus medinensis, respectively. Tropical eosinophilia is considered a frequent manifestation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Filariasis
|
c0016085
| 7,583 |
orphanet
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https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2034
| 2021-01-23T18:20:53 |
{"mesh": ["D005368"], "umls": ["C0016085"], "icd-10": ["B74.0", "B74.1", "B74.2", "B74.3", "B74.4", "B74.8", "B74.9"]}
|
Urostealith is a fatty or resinous substance identified by the Austrian chemist J. F. Heller in 1845 as the main constituent of some bladder stones.[1]
According to Heller's and other contemporary descriptions, urostealith is a soft brown substance, insoluble in water, sparingly soluble in alcohol and easily soluble in ether. Upon heating it softens at first, then expands and carbonizes before melting. It dissolves in solutions of sodium carbonate, and the latter was successfully used by Heller to dissolve and break up stones in a patient's bladder.
Urostealith stones seem to be very rare.[2] The circumstances that lead to their formation, as well as the composition of the substance, are still obscure, and little has been published on the topic.[3]
## See also[edit]
* Lipiduria
## References[edit]
1. ^ Giuliano dall'Olio (2008), Nuovo componente dei calcoli vescicali — L’ “urostealite ” di Heller. (In Italian) RIMeL - IJLaM, volume 4, issue 1, Società Italiana Medicina di Laboratorio. Online version accessed on 2009-07-30.
2. ^ S. Materazzi, R. Curini, G. D'Ascenzo, and A. D. Magri (1995), TG-FTIR coupled analysis applied to the studies in urolithiasis: characterization of human renal calculi. Termochimica Acta, volume 264, 75--93.
3. ^ Edward Wagman; Anthony Barbara; James Marquis; Marvin Chirls; Anita Falla (1966), Renal Fat Embolization and Urostealith Formation Complicating Femoral Fracture. Journal of the American Medical Association, Vol. 198, Issue 7, 721-723 Online version accessed on 2009-07-30.
This article about a disease, disorder, or medical condition 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
|
Urostealith
|
None
| 7,584 |
wikipedia
|
https://en.wikipedia.org/wiki/Urostealith
| 2021-01-18T18:43:11 |
{"wikidata": ["Q7901059"]}
|
Charcot-Marie-Tooth disease type 1E (CMT1E) is a form of Charcot-Marie-Tooth disease, which is a group of rare conditions that affect the peripheral nerves. Signs and symptoms of CMT1E generally become apparent between age 5 and 25 years, although the age of onset and disease severity can vary significantly from person to person. In general, CMT1E is associated with the typical features of Charcot-Marie-Tooth disease type 1 (progressive weakness of the feet and/or ankles; foot drop; atrophy of muscles below the knee; absent tendon reflexes of upper and lower extremities; and a decreased sensitivity to touch, heat, and cold in the feet and/or lower legs) in addition to hearing loss. CMT1E is caused by certain changes (mutations) in the PMP22 gene and 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
|
Charcot-Marie-Tooth disease type 1E
|
c3495591
| 7,585 |
gard
|
https://rarediseases.info.nih.gov/diseases/9190/charcot-marie-tooth-disease-type-1e
| 2021-01-18T18:01:31 |
{"mesh": ["C566136"], "omim": ["118300"], "orphanet": ["90658"], "synonyms": ["CMT 1E", "Charcot-Marie-Tooth disease, demyelinating, Type 1E", "Charcot-Marie-Tooth disease and deafness", "Charcot-Marie-Tooth neuropathy and deafness, autosomal dominant", "Charcot Marie Tooth disease type 1E"]}
|
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a condition that affects brain development and function. Individuals with this condition have an enlarged brain (megalencephaly) and an abnormality of the white matter in the brain (leukoencephalopathy). White matter consists of nerve fibers covered by a fatty substance called myelin that promotes the rapid transmission of nerve impulses. In MLC, the myelin is swollen and contains numerous fluid-filled pockets (vacuoles). Over time, the swelling decreases and the myelin begins to waste away (atrophy).
Leukoencephalopathy can lead to abnormal muscle tensing (spasticity), difficulty coordinating movements (ataxia), cysts in the brain (subcortical cysts), abnormal muscle tone (dystonia), swallowing difficulties, mild to moderate intellectual disabilities, speech difficulties, seizures, and difficulties walking. There are three types of MLC, which are distinguished by their signs and symptoms and genetic cause. Type 1 is caused by mutations in the MLC1 gene. Types 2A and 2B are caused by mutations in the HEPACAM gene. MLC types 1 and 2A are inherited in an autosomal recessive manner, while type 2B is inherited in an autosomal dominant manner. In approximately 5% of individuals with MLC, the cause is unknown.
Although there is no specific treatment or cure for MLC, there are ways to manage the symptoms, such as use of antiepileptic drugs, physical therapy, and speech therapy. Management additionally includes avoiding injury to the head, which can temporarily worsen symptoms. A team of doctors or specialists is often needed to figure out the treatment options for 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
|
Megalencephalic leukoencephalopathy with subcortical cysts
|
c1858854
| 7,586 |
gard
|
https://rarediseases.info.nih.gov/diseases/3445/megalencephalic-leukoencephalopathy-with-subcortical-cysts
| 2021-01-18T17:59:11 |
{"mesh": ["C536141"], "omim": ["604004"], "umls": ["C1858854"], "orphanet": ["2478"], "synonyms": ["MLC", "Vacuolating megalencephalic leukoencephalopathy with subcortical cysts", "LVM", "Megalencephaly-cystic leukodystrophy", "Leukoencephalopathy with swelling and cysts"]}
|
Hawkinsinuria is an inherited disorder, characterized by the inability to break down the amino acid tyrosine. This results in the finding of certain amino acids in the urine, such as hawkinsin. The features of this condition usually appear around the time infants are weaned off breast milk and begin to use formula. The signs and symptoms may include: failure to gain weight and grow at the expected rate (failure to thrive), abnormally high acid levels in the blood (acidosis), and fine or sparse hair. Hawkinsinuria is caused by mutations in the HPD gene and is inherited in an autosomal dominant manner. Treatment may include dietary supplements or restrictions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hawkinsinuria
|
c2931042
| 7,587 |
gard
|
https://rarediseases.info.nih.gov/diseases/5668/hawkinsinuria
| 2021-01-18T18:00:09 |
{"mesh": ["C535845"], "omim": ["140350"], "umls": ["C2931042"], "orphanet": ["2118"], "synonyms": ["4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency"]}
|
A rare vascular tumor characterized by a malignant space-occupying lesion composed of cells variably recapitulating features of normal endothelium. It mostly develops as a cutaneous tumor and is much less frequently located in the deep soft tissue. Clinical presentation is an enlarging mass, sometimes with symptoms like coagulopathy, anemia, persistent hematoma, or bruisability. Some tumors are associated with pre-existing conditions, e. g. Klippel-Trenaunay syndrome, Maffucci syndrome, or following radiation, among others. Older age, retroperitoneal location, large size, and high mitotic activity are predictors for poor outcome.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Angiosarcoma
|
c0018923
| 7,588 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263413
| 2021-01-23T17:35:35 |
{"mesh": ["D006394"], "umls": ["C0018923"], "icd-10": ["C49.9"]}
|
Most cases of this rare lesion have been nonfamilial, although Schock (1969) described the disorder in an Indian woman and 3 of her daughters. The majority of cases have been in Eskimos and in American Indians, from the Warm Springs Indians of Oregon to the Chavante Indians of Brazil. The disorder may be viral rather than genetic.
Mouth \- Focal epithelial hyperplasia of oral mucosa Inheritance \- Autosomal dominant vs. viral ▲ 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
|
FOCAL EPITHELIAL HYPERPLASIA OF THE ORAL MUCOSA
|
c1851009
| 7,589 |
omim
|
https://www.omim.org/entry/136400
| 2019-09-22T16:40:59 |
{"mesh": ["C565008"], "omim": ["136400"]}
|
Group of genetic disorders that mainly affect the bones
Osteogenesis imperfecta
Other namesBrittle bone disease,[1] Lobstein syndrome,[2] fragilitas ossium,[1] Vrolik disease,[1] osteopsathyrosis, Porak disease, Durante disease[3]
The classic blue sclerae of a person with osteogenesis imperfecta
SpecialtyPediatrics, medical genetics, osteology
SymptomsBones that break easily, blue tinge to the whites of the eye, short height, loose joints, hearing loss[1][4]
DurationLong term[4]
CausesGenetic (autosomal dominant, new mutation)[1]
Diagnostic methodBased on symptoms, DNA testing[4]
TreatmentHealthy lifestyle (exercise, no smoking), metal rods through the long bones[5]
PrognosisDepends on the type[4]
Frequency1 in 15,000 people[1]
Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones.[1][6] It results in bones that break easily.[1] The severity may be mild to severe.[1] Other symptoms may include a blue tinge to the whites of the eye, short height, loose joints, hearing loss, breathing problems and problems with the teeth.[1][4] Complications may include cervical artery dissection and aortic dissection.[7][8]
The underlying mechanism is usually a problem with connective tissue due to a lack of type I collagen.[1] This occurs in more than 90% of cases due to mutations in the COL1A1 or COL1A2 genes.[1] These genetic problems are often inherited from a person's parents in an autosomal dominant manner or occur via a new mutation.[1] There are at least eight main types, with type I being the least severe and type II the most severe.[1] Diagnosis is often based on symptoms and may be confirmed by collagen or DNA testing.[4]
There is no cure.[4] Maintaining a healthy lifestyle by exercising and avoiding smoking can help prevent fractures.[5] Treatment may include care of broken bones, pain medication, physical therapy, braces or wheelchairs and surgery.[5] A type of surgery that puts metal rods through long bones may be done to strengthen them.[5] Tentative evidence supports the use of medications of the bisphosphonate type.[9][10]
OI affects about one in 15,000 people.[1] Outcomes depend on the type of disease.[4] Most people, however, have good outcomes.[4] The condition has been described since ancient history.[11] The term "osteogenesis imperfecta" came into use in 1895 and means imperfect bone formation.[1][11]
## Contents
* 1 Signs and symptoms
* 1.1 Connective tissues
* 1.2 Hearing
* 1.3 Neurological
* 1.4 Gastrointestinal
* 1.5 Subtypes
* 1.5.1 Type I
* 1.5.2 Type II
* 1.5.3 Type III
* 1.5.4 Type IV
* 1.5.5 Type V
* 1.5.6 Type VI
* 1.5.7 Type VII
* 1.5.8 Type VIII
* 1.5.9 Type XI
* 1.5.10 Type XII
* 1.5.11 Type XIII
* 1.5.12 Type XIV
* 1.5.13 Type XV
* 1.5.14 Type XVI
* 1.5.15 Type XVII
* 1.5.16 Others
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Genetic testing
* 4.2 Differential diagnosis
* 5 Treatment
* 5.1 Bisphosphonates
* 5.2 Surgery
* 5.3 Physiotherapy
* 5.4 Physical aids
* 5.5 Teeth
* 6 History
* 7 Epidemiology
* 8 Society and culture
* 8.1 Australia
* 8.2 Canada
* 9 Other animals
* 10 References
* 11 External links
## Signs and symptoms[edit]
### Connective tissues[edit]
OI causes very thin blood vessels and may also result in people being bruised easily. The weakening of the muscles will result in bone deformities and growth issues.[citation needed]
### Hearing[edit]
About 50% of the adults with OI experience significant hearing loss, often being affected by earlier hearing loss compared to the general population. Hearing loss in OI may or may not be associated with visible deformities of the ossicles and inner ear.[12] Hearing loss frequently begins between the second and fourth decade of life, and may be conductive, sensorineural, or mixed in nature.[13]
### Neurological[edit]
OI is associated with a number of neurological abnormalities, usually involving the central nervous system, due to deformation of the skeletal structures enveloping it. Neurological complications may adversely affect life expectancy, and neurosurgical intervention may be needed to correct severe complications.[14]
### Gastrointestinal[edit]
OI may be associated with recurrent abdominal pain and chronic constipation, according to two studies on subjects affected by OI.[15][16][17]
### Subtypes[edit]
There are at least nine different types of OI. Type I is the most common. Symptoms vary from person to person.
Type Description Gene OMIM Mode of inheritance Incidence
I mild Null COL1A1 allele 166200 autosomal dominant, 60% de novo[18] 1 in 30.000[19]
II severe and usually lethal in the perinatal period COL1A1, COL1A2, 166210 (IIA), 610854 (IIB) autosomal dominant, ~100% de novo[18] 1 in 40.000[20] to 1 in 100.000[19]
III considered progressive and deforming COL1A1, COL1A2 259420 autosomal dominant, ~100% de novo[18] 1 in 60.000[19]
IV deforming, but with normal sclerae most of the time COL1A1, COL1A2 166220 autosomal dominant, 60% de novo[18]
V shares the same clinical features of IV, but has unique histologic findings ("mesh-like") IFITM5 610967 autosomal dominant[18][21]
VI shares the same clinical features of IV, but has unique histologic findings ("fish scale") SERPINF1 610968 autosomal recessive[18]
VII associated with cartilage associated protein CRTAP 610682 autosomal recessive[18]
VIII severe to lethal, associated with the protein leprecan LEPRE1, P3H1 610915 autosomal recessive
IX PPIB autosomal recessive
#### Type I[edit]
Blue sclera in osteogenesis imperfecta
Collagen is of normal quality but is produced in insufficient quantities.
* Bones fracture easily
* Slight spinal curvature
* Loose joints
* Poor muscle tone
* Discoloration of the sclera (whites of the eyes), usually giving them a blue-gray color. The blue-gray color of the sclera is due to the underlying choroidal pigment, which shows through. This is due to the sclera being thinner than normal because the defective Type I collagen is not forming correctly.
* Early loss of hearing in some children[22]
* Slight protrusion of the eyes
IA and IB are defined to be distinguished by the absence/presence of dentinogenesis imperfecta (characterized by opalescent teeth; absent in IA, present in IB). Life expectancy is slightly reduced compared to the general population due to the possibility of fatal bone fractures and complications related to OI Type I such as basilar invagination.[citation needed]
#### Type II[edit]
Collagen is not of a sufficient quality or quantity.
* Most cases result in death within the first year of life due to respiratory failure or intracerebral hemorrhage
* Severe respiratory problems due to underdeveloped lungs
* Severe bone deformity and small stature
Type II can be further subclassified into groups A, B, and C, which are distinguished by radiographic evaluation of the long bones and ribs. Type IIA demonstrates broad and short long bones with broad and beaded ribs. Type IIB demonstrates broad and short long bones with thin ribs that have little or no beading. Type IIC demonstrates thin and longer long bones with thin and beaded ribs.
#### Type III[edit]
Collagen improperly formed, enough collagen is made but it is defective.
* Bones fracture easily, sometimes even before birth
* Bone deformity, often severe
* Respiratory problems possible
* Short stature, spinal curvature and sometimes barrel-shaped rib cage
* Triangular face[23]
* Loose joints (double-jointed)
* Poor muscle tone in arms and legs
* Discolouration of the sclera (the 'whites' of the eyes are blue)
* Early loss of hearing possible
Type III is distinguished among the other classifications as being the "progressive deforming" type, wherein a neonate presents with mild symptoms at birth and develops the aforementioned symptoms throughout life. Lifespans may be normal, albeit with severe physical handicapping.
#### Type IV[edit]
Collagen quantity is sufficient, but is not of a high enough quality
* Bones fracture easily, especially before puberty
* Short stature, spinal curvature, and barrel-shaped rib cage
* Bone deformity is mild to moderate
* Early loss of hearing
Similar to Type I, Type IV can be further subclassified into types IVA and IVB characterized by absence (IVA) or presence (IVB) of dentinogenesis imperfecta.
#### Type V[edit]
X-ray of the right leg in a newborn with OI type V. There are somewhat deformed long bones (mainly the femur) with widened metaphyses. There is a cortical fracture of the fibula.
Having the same clinical features as Type IV, it is distinguished histologically by "mesh-like" bone appearance. Further characterized by the "V triad" consisting of (a) radio-opaque band adjacent to growth plates, (b) hypertrophic calluses at fracture sites, and (c) calcification of the radio-ulnar interosseous membrane.[24]
OI Type V leads to calcification of the membrane between the two forearm bones, making it difficult to turn the wrist. Another symptom is abnormally large amounts of repair tissue (hyperplasic callus) at the site of fractures. Other features of this condition include radial head dislocation, long bone bowing, and mixed hearing loss.
At least some cases of this type are caused by mutations in the IFITM5 gene.[21]
* OI Type V in an adult
* OI Type V in a child
#### Type VI[edit]
With the same clinical features as Type IV, it is distinguished histologically by "fish-scale" bone appearance. Type VI has recently been found to be caused by a loss of function mutation in the SERPINF1 gene. SERPINF1, a member of the serpin family, is also known as pigment epithelium-derived factor (PEDF), the most powerful endogenous antiangiogenic factor in mammals.
#### Type VII[edit]
In 2006, a recessive form called "Type VII" was discovered (phenotype severe to lethal). Thus far it seems to be limited to a First Nations people in Quebec.[25] Mutations in the gene CRTAP causes this type.[26]
#### Type VIII[edit]
OI caused by mutation in the gene LEPRE1 is classified as type VIII.[26]
Type IX
Osteogenesis imperfecta type IX (OI9) is caused by homozygous or compound heterozygous mutation in the PPIB gene on chromosome 15q22.[27]
Type X
Caused by homozygous mutation in the SERPINH gene on chromosome 11q13.[28]
#### Type XI[edit]
OI caused by mutations in FKBP10 on chromosome 17q21.[29] The mutations cause a decrease in secretion of trimeric procollagen molecules. These mutations can also cause autosomal recessive Bruck syndrome which is similar to OI.
#### Type XII[edit]
OI caused by a frameshift mutation in SP7. This mutation causes bone deformities, fractures, and delayed tooth eruption.[30]
#### Type XIII[edit]
OI caused by a mutation in the bone morphogenic protein 1 (BMP1) gene.[31][32] This mutation causes recurrent fractures, high bone mass, and hyperextensive joints.[33]
#### Type XIV[edit]
OI caused by mutations in the TMEM38B gene. This mutation causes recurrent fractures and osteopenia.
#### Type XV[edit]
OI caused by homozygous or compound heterozygous mutations in the WNT1 gene on chromosome 12q13. It is autosomal recessive.[34][33]
#### Type XVI[edit]
OI caused by mutations in the CREB3L1 gene. This mutation causes prenatal onset of recurrent fractures of the ribs and long bones, demineralization, decreased ossification of the skull, and blue sclerae. Family members who are heterozygous for OI XVI may have recurrent fractures, osteopenia and blue sclerae.[34]
#### Type XVII[edit]
OI caused by homozygous mutation in the SPARC gene on chromosome 5q33.
Type XVIII
OI caused by homozygous mutation in the FAM46A gene on chromosome 6q14. Characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life.[35]
#### Others[edit]
A family with recessive osteogenesis imperfecta has been reported to have a mutation in the TMEM38B gene on chromosome 9.[36] This gene encodes TRIC-B, a component of TRIC, a monovalent cation-specific channel involved in calcium release from intracellular stores.
It is extremely likely that there are other genes associated with this disease that have yet to be reported.
## Genetics[edit]
Osteogenesis imperfecta is a genetic disorder that causes increased bone fractures and collagen defects. The main causes for developing the disorder are a result of mutations in the COL1A1 and COL1A2 genes which are responsible for the production of collagen type 1.[37] Approximately 90% of people with OI are heterozygous for mutations in both the COL1A1 and COL1A2 genes.[38] There are several factors that are results of the dominant form of the OI disorder. These factors include; intracellular stress, abnormal tissue mineralization, abnormal cell to cell interactions, abnormal cell-matrix interactions, a compromised cell matrix structure, and disturbances between non-collagenous proteins and collagen.[39] Previous research lead to the belief that OI was an autosomal dominant disorder with few other variations in genomes.[40] However, In the past several years, there has been the identification of autosomal recessive forms of the disorder.[41] Recessive forms of OI relate heavily to defects in the collagen chaperones responsible for production of pro-collagen and the assembly of the related proteins.[42] Examples of collagen chaperones that are defective in OI patients include chaperone HSP47 (Cole-Carpenter syndrome) and FKBP65.[43] Mutations in these chaperones result in an improper folding pattern in the collagen 1 proteins which causes the recessive form of the disorder.[43] There are three significant types of OI that are a result of mutations in the collagen prolyl 3-hydroxylation complex (components CRTAP, P3H1, and CyPB).[43] These components are responsible for the modification of collagen a1(l)Pro986.[43] Mutations in other genes such as SP7, SERPINF1, TMEM38B and BMP1 can also lead to irregularly formed proteins and enzymes that result in the recessive form of Osteogenesis Imperfecta.[43] There are now links to defects in other proteins caused by genetic mutations ranging in function from structural proteins to enzymatic proteins.[40] A link between proteins such as pigment epithelium-derived factor (PEDF) and bone-restricted interferon-induced transmembrane protein (BRIL) are causes for type V and VI Osteogenesis Imperfecta.[44] Defects in these proteins lead to defective bone mineralization which aids in the formation of the brittle bone symptom of Osteogenesis Imperfecta.[44] Additionally, mutations in the COL1A1 and COL1A2 genes can result in signal disruptions of the extracellular matrix signaling that is present within the collagen proteins, causing worsened symptoms of the disorder.[45] A single point mutation in the untranslated 5' region of the IFITM5 gene was recently discovered and linked directly to OI type V.[46] Another single point mutation in the region that codes for collagen proteins on the IFITM5 gene was also found to be present in patients with substantially more severe versions of OI than just type V.[46] Osteogenesis imperfecta has also been seen as an X-linked related genetic disorder in some rare cases but continues to be a primarily heterozygous dominant disorder.[47]
## Pathophysiology[edit]
People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen.[48] This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure. The larger amino acid side-chains create steric hindrance that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics and the interaction between molecules, which are both compromised.[49] As a result, the body may respond by hydrolyzing the improper collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness.[50] Another suggested disease mechanism is that the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads as the homogeneous stress state found in healthy collagen fibrils is lost.[49] These recent works suggest that OI must be understood as a multi-scale phenomenon, which involves mechanisms at the genetic, nano-, micro- and macro-level of tissues. Most people with OI receive it from a parent but in 35% of cases it is an individual (de novo or "sporadic") mutation.[citation needed]
## Diagnosis[edit]
Diagnosis is typically based on medical imaging, including plain X-rays, and symptoms. Signs on medical imaging include abnormalities in all extremeties and the spine.[51] An OI diagnosis can be confirmed through DNA or collagen testing, but in many cases, the occurrence of bone fractures with little trauma and the presence of other clinical features such as blue sclera are sufficient for a diagnosis. A skin biopsy can be performed to determine the structure and quantity of type I collagen. DNA testing can confirm the diagnosis, however, it cannot exclude it because not all mutations causing OI are known and/or tested for. OI type II is often diagnosed by ultrasound during pregnancy, where already multiple fractures and other characteristic features may be present. Relative to control, OI cortical bone shows increased porosity, canal diameter, and connectivity in micro-computed tomography.[52] Severe types of OI can usually be detected before birth by using an in-vitro genetic testing technique.[53]
### Genetic testing[edit]
In order to determine whether osteogenesis imperfecta is present, genetic sequencing of the COL1A1, COL1A2, and IFITM5 genes may be done.[54][55] Duplication and deletion testing is also suggested to parents who suspect their child has OI.[54] The presence of frameshift mutations caused by duplications and deletions is generally the cause of increased severity within the disease.[54]
### Differential diagnosis[edit]
An important differential diagnosis of OI is child abuse, as both may present with multiple fractures in various stages of healing. Differentiating them can be difficult, especially when no other characteristic features of OI are present. Other differential diagnoses include rickets, osteomalacia, and other rare skeletal syndromes.
## Treatment[edit]
There is no cure.[4] Maintaining a healthy lifestyle by exercising and avoiding smoking can help prevent fractures. Treatment may include care of broken bones, pain medication, physical therapy, braces or wheelchairs, and surgery. A type of surgery that puts metal rods through long bones may be done to strengthen them.[5]
Bone infections are treated as and when they occur with the appropriate antibiotics and antiseptics.
### Bisphosphonates[edit]
In 1998, a clinical trial demonstrated the effectiveness of intravenous pamidronate, a bisphosphonate which had previously been used in adults to treat osteoporosis. In severe OI, pamidronate reduced bone pain, prevented new vertebral fractures, reshaped previously fractured vertebral bodies, and reduced the number of long-bone fractures.[56]
Although oral bisphosphonates are more convenient and cheaper, they are not absorbed as well, and intravenous bisphosphonates are generally more effective, although this is under study. Some studies have found oral and intravenous bisphosphonates, such as oral alendronate and intravenous pamidronate, equivalent.[57] In a trial of children with mild OI, oral risedronate increased bone mineral densities, and reduced nonvertebral fractures. However, it did not decrease new vertebral fractures.[58][59] A Cochrane review in 2016 concluded that though bisphosphonates seem to improve bone mineral density, it is uncertain whether this leads to a reduction in fractures or an improvement in the quality of life of individuals with osteogenesis imperfecta.[10]
Bisphosphonates are less effective for OI in adults.[60]
### Surgery[edit]
Metal rods can be surgically inserted in the long bones to improve strength, a procedure developed by Harold A. Sofield at Shriners Hospitals for Children in Chicago. During the late 1940s, Sofield, Chief of Staff at Shriners Hospitals in Chicago, worked there with large numbers of children with OI and experimented with various methods to strengthen the bones in these children.[61] In 1959, with Edward A. Miller, Sofield wrote a seminal article describing a solution that seemed radical at the time: the placement of stainless steel rods into the intramedullary canals of the long bones to stabilize and strengthen them. His treatment proved extremely useful in the rehabilitation and prevention of fractures; it was adopted throughout the world and still forms the basis for orthopedic treatment of OI.
Spinal fusion can be performed to correct scoliosis, although the inherent bone fragility makes this operation more complex in OI patients. Surgery for basilar impressions can be carried out if pressure being exerted on the spinal cord and brain stem is causing neurological problems.
### Physiotherapy[edit]
Physiotherapy is used to strengthen muscles and improve motility in a gentle manner, while minimizing the risk of fracture. This often involves hydrotherapy, light resistance exercises, and the use of support cushions to improve posture. Individuals are encouraged to change positions regularly throughout the day to balance the muscles being used and the bones under pressure.
Exercise is generally recommended.[62]
### Physical aids[edit]
With adaptive equipment such as crutches, powered wheelchairs, splints, grabbing arms, or modifications to the home, many individuals with OI can maintain a significant degree of autonomy.
### Teeth[edit]
More than 1 in 2 people with OI also have dentinogenesis imperfecta (DI) - a congenital disorder of formation of dentine.[63] Dental treatment may pose as a challenge as a result of the various deformities, skeletal and dental, due to OI. Children with OI should go for a dental check-up as soon as their teeth erupt, this may minimize tooth structure loss as a result of abnormal dentine, and they should be monitored regularly to preserve their teeth and oral health.[63]
Many people with OI are treated with bisphosphonates, and there are several complications with dental procedures when a person is taking BP, namely bisphosphonate-related osteonecrosis of the jaw (BRONJ).
## History[edit]
The condition, or types of it, has had various other names over the years and in different nations. Among some of the most common alternatives are Ekman-Lobstein syndrome, Vrolik syndrome, and the colloquial glass-bone disease. The name osteogenesis imperfecta dates to at least 1895[64] and has been the usual medical term in the 20th century to present. The current four type system began with Sillence in 1979.[65] An older system deemed less severe types "osteogenesis imperfecta tarda" while more severe forms were deemed "osteogenesis imperfecta congenita."[66] As this terminology did not differentiate well between the types, and all forms of osteogenesis are congenital, this naming convention has since fallen out of favour.
The condition has been found in an ancient Egyptian mummy from 1000 BC. The Norse king Ivar the Boneless may have had this condition, as well. The earliest studies of it began in 1788 with the Swede Olof Jakob Ekman. He described the condition in his doctoral thesis and mentioned cases of it going back to 1678. In 1831, Edmund Axmann described it in himself and two brothers. Jean Lobstein dealt with it in adults in 1833. Willem Vrolik did work on the condition in the 1850s. The idea that the adult and newborn forms were the same came in 1897 with Martin Benno Schmidt.[67]
## Epidemiology[edit]
In the United States, the incidence of osteogenesis imperfecta is estimated to be one per 20,000 live births.[68] An estimated 20,000 to 50,000 people are affected by OI in the United States. The most common types are I - IV, while the rest are very rare.[69]
Frequency is approximately the same across groups, but for unknown reasons, the Shona and Ndebele of Zimbabwe seem to have a higher proportion of Type III to Type I than other groups.[70] A similar pattern was found in segments of the Nigerian and South African populations.[citation needed] In these varied cases, the total number of OIs of all four types was roughly the same as any other ethnicity.
## Society and culture[edit]
See also: List of people with osteogenesis imperfecta
The Brittle Bone Society is a UK charity that supports people with the condition.
### Australia[edit]
The OI Society of Australia was foundation was founded in 1977. The aim is to offer information about the disease, support research, and to create awareness to the public about those with osteogenesis Imperfecta. The foundation holds a conference every two years to discuss educational events and support Wishbone Day.[71]
### Canada[edit]
The Canadian Osteogenesis Imperfecta Society was established in 1983, it is an international non-profit organization that helps with assisted living with those affected by OI. They provide emotional support, foster and support Canadian medical research in the causes of OI for all types involved. This organization also keeps and up-to-date library of medical research and findings of this disease for the public.[72]
## Other animals[edit]
In dogs, OI is an autosomal-recessive condition, meaning that dogs with two copies of the allele will be affected.[73] Beagles, Standard Wirehaired Dachshunds, Golden Retrievers, Poodles, Bedlington Terriers, Norwegian Elkhounds, and the Standard and Miniature Smooth haired Dachshund have all been known to be possible carriers of OI, as well as mice and some breeds of fish.[73] In Golden Retrievers, it is caused by a mutation in the COL1A1, and in Beagles, the COL1A2. A separate mutation in the SERPINH1 gene has been found to cause the condition in Dachshunds.[74] Many breed organizations and veterinarians offer OI tests to tell if a dog is a carrier of OI. Dogs who are heterozygous for OI should only be bred to non-carriers. Homozygous carriers should never be bred, unless it is to a non-carrier.[75]
Animal models of OI are critical to the diagnosis, treatment, and possible cure for their human counterparts. The experimental treatments and therapies used on animals play an important role in the successful treatment of OI in humans.[76] Although dogs, mice, fish, and humans are not genetically identical, some animal models have been officially recognized to represent the varying types of OI in humans. The research on animal treatment runs parallel to the success of human treatment of OI.[76]
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57. ^ DiMeglio LA, Peacock M (2006). "Two-year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta". J. Bone Miner. Res. 21 (1): 132–40. doi:10.1359/JBMR.051006. PMID 16355282. S2CID 12996685.
58. ^ Bishop Nick (2013). "Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial". Lancet. 382 (9902): 1424–1432. doi:10.1016/S0140-6736(13)61091-0. PMID 23927913. S2CID 25559791.
59. ^ Ward Leanne M (2013). "Oral bisphosphonates for paediatric osteogenesis imperfecta?". Lancet. 382 (9902): 1388–1389. doi:10.1016/S0140-6736(13)61531-7. PMID 23927912. S2CID 5872511.
60. ^ Chevrel G, Schott AM, Fontanges E, Charrin JE, Lina-Granade G, Duboeuf F, Garnero P, Arlot M, Raynal C, Meunier PJ (2006). "Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial". J. Bone Miner. Res. 21 (2): 300–6. doi:10.1359/JBMR.051015. PMID 16418786. S2CID 34089615.
61. ^ "A Leader in the Treatment of Osteogensis Imperfecta (OI)". Archived from the original on 2007-09-28. Retrieved 2007-07-05.CS1 maint: bot: original URL status unknown (link)
62. ^ "Osteogenesis Imperfecta Foundation | OIF.org". www.oif.org. Retrieved 2018-11-10.
63. ^ a b Mina Biria; Fatemeh Mashhadi Abbas; Sedighe Mozaffar; Rahil Ahmadi (2012). "Dentinogenesis imperfecta associated with osteogenesis imperfecta". Dental Research Journal. 9 (4): 489–494. PMC 3491340. PMID 23162594.
64. ^ K. Buday, Beiträge zur Lehre von der Osteogenesis imperfecta (1895)
65. ^ Sillence DO, Senn A, Danks DM (1979). "Genetic heterogeneity in osteogenesis imperfecta". J. Med. Genet. 16 (2): 101–16. doi:10.1136/jmg.16.2.101. PMC 1012733. PMID 458828.
66. ^ "Osteogenesis Imperfecta Foundation: Glossary". Archived from the original on 2007-08-07. Retrieved 2007-07-05.
67. ^ synd/1743 at Who Named It?
68. ^ Genetics of Osteogenesis Imperfecta Archived 2010-12-30 at the Wayback Machine Author: Horacio Plotkin. Updated: Feb 29, 2016
69. ^ "Osteogenesis Imperfecta Panel". University of Nebraska Medical center. Retrieved 2019-07-30.
70. ^ Viljoen D, Beighton P (1987). "Osteogenesis imperfecta type III: an ancient mutation in Africa?". Am. J. Med. Genet. 27 (4): 907–12. doi:10.1002/ajmg.1320270417. PMID 3425600.
71. ^ "The OI Society of Australia". 2006. Retrieved 6 November 2018.
72. ^ Sandor, Max (2008). "Genetic and Rare Diseases Information Center (GARD)". Retrieved 6 November 2018.
73. ^ a b "Osteogenesis Imperfecta in Dogs - Symptoms, Causes, Diagnosis, Treatment, Recovery, Management, Cost". WagWalking. Retrieved 2018-11-07.
74. ^ Eckardt J, Kluth S, Dierks C, Philipp U, Distl O (2013). "Population screening for the mutation associated with osteogenesis imperfecta in dachshunds". Vet. Rec. 172 (14): 364. doi:10.1136/vr.101122. PMID 23315765. S2CID 34816198.
75. ^ "Osteogenesis Imperfecta - CAG - Center for Animal Genetics". CAG - Center for Animal Genetics. Retrieved 2018-11-07.
76. ^ a b Carriero, Alessandra; Enderli, Tanya; Burtch, Stephanie; Templet, Jara (September 2016). "Animal models of osteogenesis imperfecta: applications in clinical research". Orthopedic Research and Reviews. 8: 41–55. doi:10.2147/ORR.S85198. ISSN 1179-1462. PMC 6209373. PMID 30774469.
## External links[edit]
Classification
D
* ICD-10: Q78.0
* ICD-9-CM: 756.51
* OMIM: 166200
* MeSH: D010013
* DiseasesDB: 9342
External resources
* MedlinePlus: 001573
* eMedicine: ped/1674
* Patient UK: Osteogenesis imperfecta
* Orphanet: 666
Wikimedia Commons has media related to Osteogenesis imperfecta.
* GeneReview/NCBI/NIH/UW entry on Osteogenesis Imperfecta
* synd/1743 at Who Named It?
* Osteogenesis Imperfecta Overview NIH Osteoporosis and Related Bone Diseases ~ National Resource Center
* v
* t
* e
Diseases of collagen, laminin and other scleroproteins
Collagen disease
COL1:
* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7
COL2:
* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)
COL3:
* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome
COL4:
* Alport syndrome
COL5:
* Ehlers–Danlos syndrome, types 1 & 2
COL6:
* Bethlem myopathy
* Ullrich congenital muscular dystrophy
COL7:
* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn
COL8:
* Fuchs' dystrophy 1
COL9:
* Multiple epiphyseal dysplasia 2, 3, 6
COL10:
* Schmid metaphyseal chondrodysplasia
COL11:
* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17:
* Bullous pemphigoid
COL18:
* Knobloch syndrome
Laminin
* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome
Other
* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21
see also fibrous proteins
* v
* t
* e
Osteochondrodysplasia
Osteodysplasia//
osteodystrophy
Diaphysis
* Camurati–Engelmann disease
Metaphysis
* Metaphyseal dysplasia
* Jansen's metaphyseal chondrodysplasia
* Schmid metaphyseal chondrodysplasia
Epiphysis
* Spondyloepiphyseal dysplasia congenita
* Multiple epiphyseal dysplasia
* Otospondylomegaepiphyseal dysplasia
Osteosclerosis
* Raine syndrome
* Osteopoikilosis
* Osteopetrosis
Other/ungrouped
* FLNB
* Boomerang dysplasia
* Opsismodysplasia
* Polyostotic fibrous dysplasia
* McCune–Albright syndrome
Chondrodysplasia/
chondrodystrophy
(including dwarfism)
Osteochondroma
* osteochondromatosis
* Hereditary multiple exostoses
Chondroma/enchondroma
* enchondromatosis
* Ollier disease
* Maffucci syndrome
Growth factor receptor
FGFR2:
* Antley–Bixler syndrome
FGFR3:
* Achondroplasia
* Hypochondroplasia
* Thanatophoric dysplasia
COL2A1 collagen disease
* Achondrogenesis
* type 2
* Hypochondrogenesis
SLC26A2 sulfation defect
* Achondrogenesis
* type 1B
* Autosomal recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
Chondrodysplasia punctata
* Rhizomelic chondrodysplasia punctata
* Conradi–Hünermann syndrome
Other dwarfism
* Fibrochondrogenesis
* Short rib – polydactyly syndrome
* Majewski's polydactyly syndrome
* Léri–Weill dyschondrosteosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Osteogenesis imperfecta
|
c0029434
| 7,590 |
wikipedia
|
https://en.wikipedia.org/wiki/Osteogenesis_imperfecta
| 2021-01-18T18:36:32 |
{"gard": ["1017"], "mesh": ["D010013"], "umls": ["C0029434", "C0023931"], "icd-9": ["756.51756.51"], "icd-10": ["Q78.078.0"], "orphanet": ["666"], "wikidata": ["Q749409"]}
|
Large granular lymphocytic leukemia
SpecialtyHematology, oncology
Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.[1]
It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells).[2]
In a study based in the US, the average age of diagnosis was 66.5 years[3] whereas in a French study the median age at diagnosis was 59 years (with an age range of 12-87 years old).[4] In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis.[4] Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population.[5]
## Contents
* 1 Signs and symptoms
* 1.1 Sites of involvement
* 2 Cause
* 3 Diagnosis
* 3.1 Laboratory findings
* 3.2 Peripheral blood
* 3.3 Bone marrow
* 3.4 Immunophenotype
* 3.5 Genetic findings
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 History
* 8 References
* 9 External links
## Signs and symptoms[edit]
This disease is known for an indolent clinical course and incidental discovery.[1] The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to anaemia and/or neutropenia[6] are seen in almost half of cases.[7][8][9][10]
Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome.[11] Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.[12]
### Sites of involvement[edit]
The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][7]
## Cause[edit]
The postulated cells of origin of T-LGLL leukemia are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases.[1]
## Diagnosis[edit]
### Laboratory findings[edit]
The requisite lymphocytosis of this disease is typically 2-20x109/L.[12]
Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.[10][13][14][15]
### Peripheral blood[edit]
The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B.[16] Flow cytometry is also commonly used.[17]
### Bone marrow[edit]
Bone marrow involvement in this disease is often present, but to a variable extent. Bone marrow biopsy is commonly used for diagnosis. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.[1]
### Immunophenotype[edit]
The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8\+ T-cell subset immunophenotype versus other permutations of those markers.[8][9] Variable expression of CD11b, CD56, and CD57[10] are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.[1]
Type Immunophenotype
Common type (80% of cases) CD3+, TCRαβ+, CD4-, CD8\+
Rare variants CD3+, TCRαβ+, CD4+, CD8\-
CD3+, TCRαβ+, CD4+, CD8\+
CD3+, TCRγδ+, CD4 and CD8 variable
### Genetic findings[edit]
Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.[14][18]
Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy.[19]
## Treatment[edit]
First line treatment is immunosuppressive therapy. A weekly dosage of Methotrexate (with or without daily Prednisone) may induce partial or complete response in some patients while others may require Cyclosporine or Cyclophosphamide.[20]
Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.[21]
Experimental data suggests that treatment with calcitrol (the active form of vitamin D) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines.[22]
## Prognosis[edit]
The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.[4]
## Epidemiology[edit]
T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.
## History[edit]
LGLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center.[23] Specimens from patients with LGLL are banked at the University of Virginia for research purposes, the only bank for such purposes.[24]
## References[edit]
1. ^ a b c d e f Elaine Sarkin Jaffe; Nancy Lee Harris; World Health Organization; International Agency for Research on Cancer; Harald Stein; J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. 3. Lyon: IARC Press. ISBN 978-92-832-2411-2.
2. ^ Epling-Burnette PK, Sokol L, Chen X, et al. (December 2008). "Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling". Blood. 112 (12): 4694–8. doi:10.1182/blood-2008-02-136382. PMC 2597136. PMID 18791165.
3. ^ Shah, M V; Hook, C C; Call, T G; Go, R S (August 2016). "A population-based study of large granular lymphocyte leukemia". Blood Cancer Journal. 6 (8): e455. doi:10.1038/bcj.2016.59. ISSN 2044-5385. PMC 5022177. PMID 27494824.
4. ^ a b c Bareau, B; Rey, J; Hamidou, M; Donadieu, J; Morcet, J; Reman, O; Schleinitz, N; Tournilhac, O; et al. (2010). "Analysis of a French cohort of patients with large granular lymphocyte leukemia: A report on 229 cases". Haematologica. 95 (9): 1534–41. doi:10.3324/haematol.2009.018481. PMC 2930955. PMID 20378561.
5. ^ Kojić Katović, Sandra (2018). "T-Cell Large Granular Lymphocytic Leukemia – Case Report". Acta Clinica Croatica. 57 (2): 362–365. doi:10.20471/acc.2018.57.02.18. ISSN 0353-9466. PMC 6531996. PMID 30431731.
6. ^ Sanikommu, Srinivasa R.; Clemente, Michael J.; Chomczynski, Peter; Afable, Manuel G.; Jerez, Andres; Thota, Swapna; Patel, Bhumika; Hirsch, Cassandra; Nazha, Aziz (2017-06-20). "Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL)". Leukemia & Lymphoma. 59 (2): 416–422. doi:10.1080/10428194.2017.1339880. ISSN 1042-8194. PMID 28633612.
7. ^ a b Lamy T, Loughran TP (January 1998). "Large Granular Lymphocyte Leukemia". Cancer Control. 5 (1): 25–33. doi:10.1177/107327489800500103. PMID 10761014.
8. ^ a b Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF (November 1986). "Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes". Blood. 68 (5): 1142–53. PMID 3490288.
9. ^ a b Pandolfi F, Loughran TP, Starkebaum G, et al. (January 1990). "Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study". Cancer. 65 (2): 341–8. doi:10.1002/1097-0142(19900115)65:2<341::AID-CNCR2820650227>3.0.CO;2-2. PMID 2403836.
10. ^ a b c Lamy T, Loughran TP (July 2003). "Clinical features of large granular lymphocyte leukemia". Semin. Hematol. 40 (3): 185–95. doi:10.1016/S0037-1963(03)00133-1. PMID 12876667.
11. ^ Loughran TP, Starkebaum G, Kidd P, Neiman P (January 1988). "Clonal proliferation of large granular lymphocytes in rheumatoid arthritis". Arthritis Rheum. 31 (1): 31–6. doi:10.1002/art.1780310105. PMID 3345230.
12. ^ a b Kwong YL, Wong KF (September 1998). "Association of pure red cell aplasia with T large granular lymphocyte leukaemia". J. Clin. Pathol. 51 (9): 672–5. doi:10.1136/jcp.51.9.672. PMC 500904. PMID 9930071.
13. ^ Oshimi K, Yamada O, Kaneko T, et al. (June 1993). "Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders". Leukemia. 7 (6): 782–8. PMID 8388971.
14. ^ a b Loughran TP, Starkebaum G, Aprile JA (March 1988). "Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia". Blood. 71 (3): 822–4. PMID 3345349.
15. ^ Loughran TP, Kadin ME, Starkebaum G, et al. (February 1985). "Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia". Ann. Intern. Med. 102 (2): 169–75. doi:10.7326/0003-4819-102-2-169. PMID 3966754.
16. ^ Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP (January 1997). "The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis". Blood. 89 (1): 256–60. PMID 8978299.
17. ^ Lamy, Thierry; Loughran, Thomas P. (2011-03-10). "How I treat LGL leukemia". Blood. 117 (10): 2764–2774. doi:10.1182/blood-2010-07-296962. ISSN 0006-4971. PMC 3062292. PMID 21190991.
18. ^ Vie H, Chevalier S, Garand R, et al. (July 1989). "Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder". Blood. 74 (1): 285–90. PMID 2546620.
19. ^ Shi, Min; He, Rong; Feldman, Andrew L.; Viswanatha, David S.; Jevremovic, Dragan; Chen, Dong; Morice, William G. (March 2018). "STAT3 mutation and its clinical and histopathologic correlation in T-cell large granular lymphocytic leukemia". Human Pathology. 73: 74–81. doi:10.1016/j.humpath.2017.12.014. ISSN 0046-8177. PMID 29288042.
20. ^ Sanikommu, Srinivasa R.; Clemente, Michael J.; Chomczynski, Peter; Afable, Manuel G.; Jerez, Andres; Thota, Swapna; Patel, Bhumika; Hirsch, Cassandra; Nazha, Aziz (2017-06-20). "Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL)". Leukemia & Lymphoma. 59 (2): 416–422. doi:10.1080/10428194.2017.1339880. ISSN 1042-8194. PMID 28633612.
21. ^ Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH (March 2004). "Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia". Blood. 103 (5): 1969–71. doi:10.1182/blood-2003-11-3951. PMID 14976065.
22. ^ Olson, Kristine C.; Kulling, Paige M.; Olson, Thomas L.; Tan, Su-Fern; Rainbow, Rebecca J.; Feith, David J.; Loughran, Thomas P. (2016-10-07). "Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukemia". Cancer Biology & Therapy. 18 (5): 290–303. doi:10.1080/15384047.2016.1235669. ISSN 1538-4047. PMC 5499847. PMID 27715403.
23. ^ https://cancer.uvahealth.com/LGLLeBookNew.pdf
24. ^ "LGL Leukemia Program | UVA Health System".
## External links[edit]
Classification
D
* ICD-O: 9831/3
* MeSH: D054066
* v
* t
* e
Leukaemias, lymphomas and related disease
B cell
(lymphoma,
leukemia)
(most CD19
* CD20)
By
development/
marker
TdT+
* ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
CD5+
* naive B cell (CLL/SLL)
* mantle zone (Mantle cell)
CD22+
* Prolymphocytic
* CD11c+ (Hairy cell leukemia)
CD79a+
* germinal center/follicular B cell (Follicular
* Burkitt's
* GCB DLBCL
* Primary cutaneous follicle center lymphoma)
* marginal zone/marginal zone B-cell (Splenic marginal zone
* MALT
* Nodal marginal zone
* Primary cutaneous marginal zone lymphoma)
RS (CD15+, CD30+)
* Classic Hodgkin lymphoma (Nodular sclerosis)
* CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma)
PCDs/PP
(CD38+/CD138+)
* see immunoproliferative immunoglobulin disorders
By infection
* KSHV (Primary effusion)
* EBV
* Lymphomatoid granulomatosis
* Post-transplant lymphoproliferative disorder
* Classic Hodgkin lymphoma
* Burkitt's lymphoma
* HCV
* Splenic marginal zone lymphoma
* HIV (AIDS-related lymphoma)
* Helicobacter pylori (MALT lymphoma)
Cutaneous
* Diffuse large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Primary cutaneous marginal zone lymphoma
* Primary cutaneous immunocytoma
* Plasmacytoma
* Plasmacytosis
* Primary cutaneous follicle center lymphoma
T/NK
T cell
(lymphoma,
leukemia)
(most CD3
* CD4
* CD8)
By
development/
marker
* TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
* prolymphocyte (Prolymphocytic)
* CD30+ (Anaplastic large-cell lymphoma
* Lymphomatoid papulosis type A)
Cutaneous
MF+variants
* indolent: Mycosis fungoides
* Pagetoid reticulosis
* Granulomatous slack skin
aggressive: Sézary disease
* Adult T-cell leukemia/lymphoma
Non-MF
* CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
* Pleomorphic T-cell lymphoma
* Lymphomatoid papulosis type B
* CD30+: CD30+ cutaneous T-cell lymphoma
* Secondary cutaneous CD30+ large-cell lymphoma
* Lymphomatoid papulosis type A
Other
peripheral
* Hepatosplenic
* Angioimmunoblastic
* Enteropathy-associated T-cell lymphoma
* Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma)
* Subcutaneous T-cell lymphoma
By infection
* HTLV-1 (Adult T-cell leukemia/lymphoma)
NK cell/
(most CD56)
* Aggressive NK-cell leukemia
* Blastic NK cell lymphoma
T or NK
* EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
* Large granular lymphocytic leukemia
Lymphoid+
myeloid
* Acute biphenotypic leukaemia
Lymphocytosis
* Lymphoproliferative disorders (X-linked lymphoproliferative disease
* Autoimmune lymphoproliferative syndrome)
* Leukemoid reaction
* Diffuse infiltrative lymphocytosis syndrome
Cutaneous lymphoid hyperplasia
* Cutaneous lymphoid hyperplasia
* with bandlike and perivascular patterns
* with nodular pattern
* Jessner lymphocytic infiltrate of the skin
General
* Hematological malignancy
* leukemia
* Lymphoproliferative disorders
* Lymphoid leukemias
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Large granular lymphocytic leukemia
|
c1955861
| 7,591 |
wikipedia
|
https://en.wikipedia.org/wiki/Large_granular_lymphocytic_leukemia
| 2021-01-18T18:59:54 |
{"gard": ["9812"], "mesh": ["D054066"], "umls": ["C1955861"], "icd-10": ["C91.7"], "orphanet": ["86872"], "wikidata": ["Q6489151"]}
|
A number sign (#) is used with this entry because of evidence that resistance and sensitivity to coumarin (warfarin) treatment can be influenced by variations in several genes, including CYP2A6 (122720), VKORC1 (608547), CYP2C9 (601130), and CYP4F2 (604426).
Coumarin sensitivity can also result from certain mutations in the factor IX gene (e.g., 300746.0103).
Description
Warfarin is a widely prescribed anticoagulant for the prevention of thromboembolic diseases for subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement (Yuan et al., 2005). The dose requirement is highly variable, both interindividually and interethnically.
Variation in the VKORC1 gene is believed to be the most important individual predictor of warfarin dose, accounting for about 30% of the variance observed in dosing (Ross et al., 2010).
Clinical Features
O'Reilly et al. (1964) described resistance to the hypoprothrombinemic effects of coumarin drugs in 7 persons in 3 generations of a family with no male-to-male transmission. They postulated that an autosomal gene is responsible for the synthesis of a clotting factor dependent on vitamin K and that in this family affected persons have an abnormal factor with decreased affinity for the coumarin drug or increased affinity for vitamin K. O'Reilly (1970) described a second kindred of which 18 members were shown to have relative resistance to oral anticoagulant drugs. Several instances of male-to-male transmission were observed. Of the various possible mechanisms for the relative resistance, all could be excluded except mutation in the vitamin K-anticoagulant receptor site. Positive evidence favoring the latter included the correction of hypoprothrombinemia by small amounts of exogenous vitamin K and the fact that the anticoagulant dose-response curves for the probands of the 2 families studied by O'Reilly and normal subjects are parallel. Pool et al. (1968) concluded that the resistance to warfarin is due to a decreased affinity of the receptor sites in the liver to coumarin anticoagulant drugs. This mendelian variation must be distinguished from the polygenic variation in coumarin responsiveness due to variations in metabolism of the drug.
Lewis et al. (1967) reported a single patient with warfarin resistance resulting from abnormally rapid clearance of the drug. Resistance to phenindione, a drug of different structure, was also demonstrated.
Alving et al. (1985) reported a black family in which the proposita and her daughter had relative resistance to the anticoagulant effects of warfarin. A diet deficient in vitamin K was accompanied by enhanced effects of warfarin. For vitamin K to participate in the carboxylation of factors II, VII, IX, and X, it must be in a reduced form. It becomes an epoxide as carboxylation occurs and is recycled to its reduced form by a vitamin K reductase (Whitlon et al., 1978). Warfarin has an inhibitory effect on the reductase. The genetic defect in warfarin resistance in both man and rat may result in an altered affinity of the enzyme for the drug.
Mapping
Kohn and Pelz (2000) mapped the warfarin-resistance locus of the rat, Rw, and placed the ortholog on mouse chromosome 7 and 3 candidate human chromosomes, including 10q25.3-q26. The CYP2C9 gene maps to chromosome 10q24.
Molecular Genetics
Rost et al. (2004) identified 4 different heterozygous mutations in the VKORC1 gene (608547.0002-608547.0005), encoding vitamin K epoxide reductase, in individuals with warfarin resistance.
In 45 patients, Shikata et al. (2004) analyzed mutations of 7 genes encoding vitamin K-dependent proteins and the CYP2C9 (601130) gene and investigated whether any contributed to the large interpatient variability in the warfarin dose-effect relationship. Multiple regression analysis revealed that warfarin sensitivity was independently associated with the -402G-A polymorphism of the factor VII gene (F7; 613878), the CAA repeat of the gamma-glutamyl carboxylase gene (GGCX; 137167), CYP2C9*3 (601130.0001), and the thr165-to-met (T165M) polymorphism of the factor II gene (F2; 176930).
In a genomewide analysis of 181 white individuals taking warfarin, Cooper et al. (2008) found that the most significant independent effect of variation in warfarin maintenance dose was conferred by SNPs in the VKORC1 gene (p = 6.2 x 10(-13)), with lesser associations with SNPs the CYP2C9 gene (p = 10(-4)). These associations were replicated in 2 populations, yielding combined p values of 4.7 x 10(-34) and 6.2 x 10(-12) for VKORC1 and CYP2C9, respectively. The warfarin dose variance explained by the 2 genes was estimated to be 25% and 9%, respectively. No significant associations with other SNPs were identified, and Cooper et al. (2008) concluded that the VKORC1 and CYP2C9 genes are the primary genetic determinants of stabilized warfarin dose and that common SNPs with large effects on warfarin dose are unlikely to be discovered outside of these 2 genes.
Among 273 African Americans and 302 European Americans undergoing warfarin therapy, Limdi et al. (2008) found that variation in the VKORC1 gene could explain 5% and 18%, respectively, of variability in warfarin dosage. An additive effect was observed when also accounting for polymorphisms in the CYP2C9 gene (8% and 30%, in African Americans and European Americans, respectively). Four common VKORC1 haplotypes were identified in European Americans, and 12 in African Americans, consistent with higher genomic sequence diversity in populations of African descent. African Americans had a lower frequency of the low-dose haplotype compared with European Americans (10.6% vs 35%, p less than 0.0001). The variability in dose explained by VKORC1 haplotype or haplotype groups was similar to that of a single informative polymorphism. Two SNPs in the VKORC1 gene (rs9934438) or (rs9923231) were best predictors of warfarin dose in both groups.
The International Warfarin Pharmacogenetics Consortium (2009) found that a pharmacogenetic dose algorithm for warfarin based on the genotype at VKORC1 and CYP2C9 accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and those who required 49 mg or more per week to achieve the targeted international normalized ratio than did a clinical algorithm alone (49.4% vs 33.3%, p less than 0.001, among patients requiring 21 mg or less per week; and 24.8% vs 7.2%, p less than 0.001, among those requiring 49 mg or more per week). The authors concluded that the use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.
Using the Affymetrix drug-metabolizing enzymes and transporters (DMET) assay to screen SNPS from 144 genes involved in drug metabolism, Caldwell et al. (2008) found an association between a C-to-T transition (rs2108622) in the CYP4F2 gene (604426) and warfarin dose variance among individuals on warfarin therapy (p = 2.4 x 10(-7)). The findings were replicated in 2 additional cohorts, yielding a total of 1,051 individuals for all 3 cohorts. CC homozygotes required less warfarin, TT homozygotes required more warfarin, and CT heterozygotes required intermediate doses to achieve a therapeutic effect. The minor allele frequency in whites and Asians is approximately 30%, compared to 7% in blacks, predicting a lesser effect of this SNP in blacks as a population.
Borgiani et al. (2009) also reported an association between rs2108622 in the CYP4F2 gene and warfarin dose variance among 141 Italian individuals on warfarin therapy. TT homozygotes required 5.49 mg/day compared to 2.93 mg/day for CC homozygotes. Analysis of variance indicated that about 7% of mean weekly warfarin dose variance could be explained by CYP4F2 genotype. A linear regression model including CYP4F2, CYP2C9 and VKORC1 genetic variants, age, and weight, could explain 60.5% of the interindividual variability.
In a genomewide association study of 1,053 Swedish individuals, Takeuchi et al. (2009) found a significant association between warfarin dose and 2 main regions: SNPs clustering near the VKORC1 gene (p less than 10(-78)) and SNPs near CYP2C9 (p less than 10(-31)). Multiple regression analyses adjusting for known influences on warfarin dose (VKORC1, CYP2C9, age, gender) allowed further identification of an association with rs2108622 (p = 8.3 x 10(-10)) in the CYP4F2 gene. SNPs in and near the VKORC1 and CYP2C9 genes explained about 30% and 12%, of warfarin dose variance, respectively, whereas the SNP in the CYP4F2 gene explained about 1.5% of the dose variance.
Population Genetics
In an editorial, Shurin and Nabel (2007) noted that evidence from various clinical and population studies suggested that patients of Asian, European, and African ancestry require, on average, lower, intermediate, and higher doses of warfarin, respectively. They suggested that additional studies involving larger numbers of patients of African and Asian descent were needed to confirm these associations (Takahashi et al., 2006).
Ross et al. (2010) reported frequency analysis of 4 SNPs affecting warfarin dosage in 963 individuals from 7 geographic regions worldwide and in 316 Canadians of European, East Asian, and South Asian ancestry. The SNPs analyzed included rs9923231 in the VKORC1 gene (608547.0006); rs1799853 and rs1057910, both in the CYP2C9 gene (601130.0002 and 601130.0001, respectively); and rs2108622 in the CYP4F2 gene (604426). The VKORC1 SNP showed the highest differentiation in allele frequency among different geographic regions.
Animal Model
Hereditary resistance to warfarin in rats, which may be a comparable condition, is inherited as an autosomal dominant (Greaves and Ayres, 1967). A single gene difference in ability to 7-hydroxylate coumarin is known in mice (Wood and Conney, 1974). The gene locus, called Coh, is known to be on chromosome 7 of the mouse (see mouse gene map in fifth edition of Mendelian Inheritance in Man).
Lush and Andrews (1978) suggested that there may be 2 closely linked genes on mouse chromosome 7 determining cytochrome P-450 isozymes with different substrate specificities. Coumarin-7-hydroxylase in the mouse is encoded by a gene, symbolized Cyp2a-5 (Nebert et al., 1991), in the P450C2A family. (The CYP2A subfamily has many genes in which the orthologs in different species cannot be established for certain; therefore, each gene, as it becomes characterized, regardless of the species, is given the next available number (Nebert, 1994). When the human CYP2A3 gene was cloned, it was shown to encode IIA3, the enzyme for coumarin-7-hydroxylase (Yamano et al., 1990). Unfortunately, the CYP2A3 designation had already been taken for the rat gene and it was uncertain that the human gene was orthologous to the rat gene. Therefore, the human IIA3 gene product is encoded by a gene which is now designated CYP2A6 (Nebert, 1994).)
Lindberg et al. (1992) compared the Coh locus in mouse strains having high coumarin 7-hydroxylase activity (H) with those having low activity (L). The nucleotide sequences of cDNAs from the 2 strains differed by a single base, which resulted in an amino acid difference at position 117: val in P450coh(H) and ala in P450coh(L). They found evidence that a recent duplication in the ancestral mouse established the line of descent from the ancestral P450coh gene to the P450 enzyme with steroid 15-alpha-hydroxylase activity. During evolution, amino acid substitutions occurred selectively at positions that altered the enzyme's substrate specificity and increased its specific activity.
Inheritance \- Autosomal dominant Lab \- Decreased affinity of liver receptors for coumarin Heme \- Warfarin resistance ▲ 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
|
COUMARIN RESISTANCE
|
c0750384
| 7,592 |
omim
|
https://www.omim.org/entry/122700
| 2019-09-22T16:42:50 |
{"mesh": ["C563039"], "omim": ["122700"], "synonyms": ["Alternative titles", "COUMARIN, POOR METABOLISM OF", "WARFARIN RESISTANCE"]}
|
A number sign (#) is used with this entry because of evidence that infantile hypercalcemia-1 (HCINF1) is caused by homozygous or compound heterozygous mutation in the CYP24A1 gene (126065) on chromosome 20q13.
Description
Infantile hypercalcemia is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. An epidemic of idiopathic infantile hypercalcemia occurred in the United Kingdom in the 1950s after the implementation of an increased prophylactic dose of vitamin D supplementation; however, the fact that most infants receiving the prophylaxis remained unaffected suggested that an intrinsic hypersensitivity to vitamin D might be implicated in the pathogenesis (summary by Schlingmann et al., 2011).
### Genetic Heterogeneity
Infantile hypercalcemia-2 (HCINF2; 616963) is caused by mutation in the SLC34A1 gene (182309) on chromosome 5q35.
Clinical Features
Suspicion of a genetic basis of hypercalcemia was provided by the family reported first by Smith et al. (1959) and later by Kenny et al. (1963). Two sisters were affected. The authors suggested that the defect might concern vitamin D inactivation. The parents had normal serum calcium levels. The mother, but not the father, became hypercalcemic with a small dose of added vitamin D (Blizzard, 1963; Ehrhardt and Money, 1967).
Hooft et al. (1961) described a family in which a child had idiopathic hypercalcemia and the father had sarcoidosis with hypercalcemia. Autosomal dominant inheritance was suggested by the family reported by Mehes et al. (1975), in which there was an affected father, son, and daughter.
Schlingmann et al. (2011) studied 4 infants from 4 unrelated families, 1 of which was consanguineous, who presented between the ages of 6 and 8 months with typical symptoms of hypercalcemia, including weight loss or failure to thrive, polyuria or dehydration, and muscular hypotonia or lethargy. All 4 infants had received 500 IU of oral vitamin D supplementation daily since birth. Laboratory evaluation revealed profound hypercalcemia, suppressed intact parathyroid hormone (PTH; 168450), and hypercalciuria. Renal ultrasound showed medullary nephrocalcinosis. The authors noted that even after discontinuation of oral vitamin D and institution of a low-calcium diet, serum calcium levels in these patients tended to be continuously mildly elevated during follow-up, and intact PTH levels remained suppressed. Evaluation of 2 asymptomatic sibs of 2 of the patients revealed that 1, who was the monozygotic twin of the affected sib, had an elevated serum calcium level, suppressed intact PTH, hypercalciuria, and medullary nephrocalcinosis. The other sib, who had not been given vitamin D prophylaxis due to his older brother's medical history, was found at 18 months of age to have a serum calcium level in the normal range, suppression of intact PTH, and medullary hyperechogenicity on renal ultrasound.
### Phenotypic Variability
Streeten et al. (2011) studied a 47-year-old man who had an episode of nephrolithiasis at 19 years of age and was subsequently asymptomatic until 39 years of age, when hypercalcemia was discovered on routine testing. The patient had a suppressed parathyroid hormone level, elevated levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and low levels of 24,25-dihydroxyvitamin D. After identification of a homozygous mutation in the CYP24A1 gene in this patient (see MOLECULAR GENETICS), Streeten et al. (2011) proposed that in some patients with reduced 24-hydroxylase activity, tissue resistance to 1,25-dihydroxyvitamin D might develop over time, blunting the hypercalcemic response, a concept supported by their patient's normal bone mineral density.
Inheritance
Infantile hypercalcemia is inherited as an autosomal recessive trait (Schlingmann et al., 2011).
Pathogenesis
Esterification with fatty acids is a protective mechanism against excessive amounts of 1,25-dihydroxyvitamin D. Weisman et al. (1979) suggested that deficiency of the esterification mechanism may underlie infantile hypercalcemia. They suggested that complete absence of normal esterification might cause a severe form of the disorder even when vitamin D intake is not excessive, whereas mild cases may be due to partial deficiency in combination with large intake of vitamin D.
Molecular Genetics
In 4 probands and 2 asymptomatic sibs with idiopathic infantile hypercalcemia from 4 unrelated families, including a Turkish family of known consanguinity, Schlingmann et al. (2011) analyzed 4 candidate genes involved in vitamin D metabolism and identified homozygosity or compound heterozygosity for 6 different mutations in the CYP24A1 gene (126065.0001-126065.0006, respectively). Analysis of CYP24A1 in 4 unrelated German patients who developed symptomatic hypercalcemia in infancy after receiving 1 or more oral doses of 600,000 IU of vitamin D2, 2 of whom were previously reported (Misselwitz and Hesse, 1986), revealed homozygosity or compound heterozygosity for 2 CYP24A1 mutations in 3 patients (126065.0005; 126065.0007). In 1 of the German patients, a heterozygous complex deletion in CYP24A1 was identified, but no other mutation was detected by sequence analysis.
In a 47-year-old man with a history of nephrolithiasis at 20 years of age and asymptomatic hypercalcemia discovered at 39 years of age, Streeten et al. (2011) identified homozygosity for a 3-bp deletion in the CYP24A1 gene (E143del; 126065.0002). The authors noted that this mutation had previously been identified in patients with infantile hypercalcemia, suggesting variable severity and possibly age-related phenotypic change. Schlingmann et al. (2011) commented that this case widened the phenotypic spectrum found in patients with CYP24A1 defects and suggested that the penetrance of such mutations might well be incomplete; they noted that information on lifestyle, nutrition, and vitamin supplementation in the patient described by Streeten et al. (2011) might identify a potential trigger for the development of clinical symptoms in adulthood.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Weight loss Other \- Failure to thrive ABDOMEN Gastrointestinal \- Vomiting GENITOURINARY Kidneys \- Polyuria \- Nephrocalcinosis \- Nephrolithiasis (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Lethargy METABOLIC FEATURES \- Suppression of intact parathyroid hormone levels LABORATORY ABNORMALITIES \- Hypercalcemia \- Hypercalciuria \- Dehydration MISCELLANEOUS \- Most patients develop symptoms while on prophylactic vitamin D supplementation in infancy \- Some patients may not present until adulthood MOLECULAR BASIS \- Caused by mutation in cytochrome P450, family 24, subfamily A, polypeptide-1 gene (CYP24A1, 126065.0001 ) ▲ 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
|
HYPERCALCEMIA, INFANTILE, 1
|
c0268080
| 7,593 |
omim
|
https://www.omim.org/entry/143880
| 2019-09-22T16:40:09 |
{"mesh": ["C562581"], "omim": ["143880"], "orphanet": ["300547"], "synonyms": ["Alternative titles", "HYPERCALCEMIA, IDIOPATHIC, OF INFANCY", "Familial infantile hypercalcemia with suppressed intact parathyroid hormone"]}
|
For muscular fiber damage, see Tendinitis.
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Find sources: "Tenonitis" – news · newspapers · books · scholar · JSTOR (September 2017) (Learn how and when to remove this template message)
Tenonitis
SpecialtyOphthalmology
Tenonitis is an rare eye disease[1] that is represented by inflammation of the Tenon capsule.[2] The Tenon Capsule, also known as the fascial sheath of the eyeball, is a structure surrounding the eyeball, and when it becomes inflamed it may cause issues in regards to vision. Also known as orbital tenonitis, tenonitis is associated with the SLC26A3 gene.[3] The inflammation of the Tenon Capsule resulting from heightened blood flow may also affect the lacrimal gland and the extraocular muscles.
Eye anatomy
## Contents
* 1 Signs and Symptoms
* 2 Causes
* 3 Mechanism
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 Research Directions
* 9 References
## Signs and Symptoms[edit]
Signs and symptoms depend on the severity of the case with tenonitis. In mild cases it may just be an uncomfortable sensation in the eye socket. In extreme cases it may cause permanent blindness or eye removal is needed.
* Swelling
* Intraocular pressure
* Blindness
*
## Causes[edit]
There are no specific causes of this disease. With this being so rare not enough research has been allocated to pinpoint a specific cause of this disease. The main thing that we know about this disease is that the inflammation of the Tenon Capsule may be related to macular retinal edema and intraocular pressure quantitative trait locus.[3]
## Mechanism[edit]
With the lack of research and understanding about this specific disease it is hard to come up with a mechanism that outlines how this arises in the body. Although we cannot pinpoint specifically how it occurs, there are some findings that may help us get to that point in the future. A gene that is associated with orbital tenonitis is the SLC26A3 gene. This gene mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes.[4] It is also known that related phenotypes are Increased shRNA abundance (Z-score > 2). [3]
## Diagnosis[edit]
Tenonitis can be identified and diagnosed a few different ways. The tenon's capsule may have inflammation from a disease called idiopathic orbital inflammation syndrome.[5] There is no history of trauma or adjacent focus of infection with this disease. In order to diagnose tenonitis some type of imaging is needed, such as a CT or MRI. The imaging is used to capture the inflammation and to spot any possible chance of infection. For chronic diseases a biopsy may be needed to determine an underlying condition that may be causing the recurring inflammation.[6]
## Treatment[edit]
The main course of treatment for this specific disease would be to surgically excise the tenon capsule. There is no info that implies the inflammation of this capsule will go down over time so the known course of action would be to have it surgically removed in order to relieve uncomfortably and to prevent further irritation to this area.[7]
## Prognosis[edit]
Although this may not be a lethal disease it will progressively get worse overtime. Depending on the severity of the disease this may have months of progression. When going past 3 months of having issues the main course of action would be to surgically relieve the pain or total excision of the affected area.
## Epidemiology[edit]
This disease has no specific population it targets more. With the information that is provided by previous research, this is a typically universal disease that can affect any population.
## Research Directions[edit]
Currently there haven't been many studies conducted in regards to the tenon capsule. In one study the objective was to see the efficacy of excision of the tenon capsule by way of trabeculectomy alone, and also combined with partial tenonectomy.[8] There is further research needed to be done to determine the cause of this specific disease, what happens during the progression of it, and treatment plans that need to be put in place.[8]
## References[edit]
1. ^ Schlossberg, David (2012). Infections of the Head and Neck. Springer Science & Business Media. p. 38. ISBN 9781461246404. Retrieved 10 September 2017.
2. ^ "Tenon capsule", Wikipedia, 2020-02-08, retrieved 2020-11-12
3. ^ a b c "Orbital Tenonitis disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2020-11-12.
4. ^ "Chloride anion exchanger", Wikipedia, 2020-10-12, retrieved 2020-11-12
5. ^ Espinoza, Gabriela M. (2010-12-01). "Orbital Inflammatory Pseudotumors: Etiology, Differential Diagnosis, and Management". Current Rheumatology Reports. 12 (6): 443–447. doi:10.1007/s11926-010-0128-8. ISSN 1534-6307.
6. ^ "Inflammatory Orbital Disease - Eye Disorders". Merck Manuals Professional Edition. Retrieved 2020-12-15.
7. ^ Dubey, Suneeta; Singh, Nishtha (March 2017). "Excision of the Tenon Capsule in Pediatric Trabeculectomy". Journal of Glaucoma. 26 (3): e126–e127. doi:10.1097/IJG.0000000000000469. ISSN 1057-0829.
8. ^ a b Awadein, Ahmed; El Sayed, Yasmine M. (2016-01-01). "Excision of Tenon Capsule in Pediatric Trabeculectomy: A Controlled Study". Journal of Glaucoma. 25 (1): 39–44. doi:10.1097/IJG.0000000000000220.
This article about an ophthalmic disease 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
|
Tenonitis
|
c0155259
| 7,594 |
wikipedia
|
https://en.wikipedia.org/wiki/Tenonitis
| 2021-01-18T19:02:17 |
{"umls": ["C0155259"], "wikidata": ["Q7700555"]}
|
A number sign (#) is used with this entry because of evidence that autosomal dominant osteopetrosis-3 (OPTA3) is caused by heterozygous mutation in the PLEKHM1 gene (611466) on chromosome 17q21.
An autosomal recessive form of osteopetrosis (OPTB6; 611497) is also caused by mutation in the PLEKHM1 gene.
Description
Autosomal dominant osteopetrosis-3 is characterized by phenotypic variability. Some patients have typical features of osteopetrosis, including fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density, whereas other patients exhibit localized osteosclerosis and generalized osteopenia. OPTA3 represents a relatively malignant form of osteopetrosis in some patients who develop significant pancytopenia and hepatosplenomegaly (Bo et al., 2016).
For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634).
Clinical Features
Del Fattore et al. (2008) studied a 39-year-old Italian woman with an atypical osteopetrosis phenotype. At 3 years of age, she was diagnosed with rickets, and at age 28, with osteoporosis and vitamin D3 deficiency. X-rays at age 22 showed a modest increase in the thickness of the internal cortex of the frontal bone, and by age 31 there was a marked increase in thickness and hyperostosis in that bone segment. At age 36, x-rays showed radiolucent regions with inner discrete areas of increased bone density in the left femoral head and in the distal metaphysis of the right femur. At age 39, the patient experienced recurrent headaches, and skull x-rays showed a 5-mm radiolucent area in the frontoparietal bone that was osteolytic on CT scan but not metabolically active on scintigraphy. In addition, there was intense radiodensity of the skull base, osteophytes of the lumbar vertebral bodies, and osteolytic areas in the left femoral neck. Serum parathyroid hormone (PTH; 168450), osteocalcin (BGLAP; 112260), and tartrate-resistant acid phosphatase (TRACP) were elevated. The patient was diagnosed with osteopetrosis of the skull, but the authors noted that she also exhibited generalized osteopenia.
Bo et al. (2016) reported a 'middle-aged' Chinese man who presented with a history of frequent fractures, weakness, and fatigue. Examination revealed pale conjunctivae, pectus carinatum, 4 missing teeth, and hepatosplenomegaly, with reduced hemoglobin, white blood cell, and platelet levels, as well as significantly elevated PTH levels. X-rays showed generalized osteosclerosis of the cranial vault, cranial base, vertebrae, ribs, pelvis, and limbs. The calvarium was thickened and sclerotic, and the thoracic and lumbar spine exhibited intense radiodensity, with the typical 'sandwich vertebra' and 'bone-within-bone' appearance. There was increased density of the central pelvic bones, and a generalized increase in bone mineral density of the long bones. Radionuclide bone imaging revealed increased activity in the long bones and large joints as well as in the metacarpals bilaterally. Vertebral body bone biopsy exhibited the hallmarks of osteopetrosis, including unabsorbed calcified cartilage surrounded by bone and osteoclast aggregation, with obvious narrowing of the bone marrow cavity. Vision and hearing were normal, and there were no apparent neurologic deficits in the proband. His father reported excessive loss of teeth, but his mother, 2 sisters, and son and daughter were healthy, and radiologic and laboratory examinations of these relatives were unremarkable. Clinical follow-up in the proband over 4 years showed persistent significant anemia and hepatosplenomegaly despite treatment, indicating a relatively malignant form of osteopetrosis.
Molecular Genetics
In a 39-year-old Italian woman with osteopetrosis of the skull and generalized osteopenia, who was negative for mutation in the CLCN7 gene (602727), Del Fattore et al. (2008) analyzed the candidate gene PLEKHM1 and identified heterozygosity for a missense mutation (R714C; 611466.0002) that was not found in 48 Italian or 56 Belgian controls, nor in 30 additional osteopetrotic patients. Family members were unavailable for evaluation.
In a 'middle-aged' Chinese man with a relatively malignant form of osteopetrosis with significant anemia and hepatosplenomegaly, who was negative for mutation in the CLCN7 and TNFSF11 (602642) genes, Bo et al. (2016) identified heterozygosity for a de novo 2-bp deletion in the PLEKHM1 gene (611466.0003) which was not present in unaffected family members.
INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Missing teeth ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Recurrent fractures with minor trauma \- Generalized osteopenia (in 1 patient) Skull \- Thickened calvarium \- Sclerotic calvarium \- Localized osteosclerosis of the skull Spine \- Radiodense spine \- Osteophytes of vertebral bodies \- 'Sandwich' vertebrae \- 'Bone-within-bone' appearance of vertebrae \- Narrowing of bone marrow cavity Pelvis \- Increased density of central pelvic bones Limbs \- Generalized increase in density of long bones \- Radiolucent areas in femoral head \- Discrete areas of increased bone density in femoral head ENDOCRINE FEATURES \- Elevated parathyroid hormone (PTH) HEMATOLOGY \- Anemia \- Reduced white blood cell count \- Reduced platelet count LABORATORY ABNORMALITIES \- Elevated acid phosphatase MISCELLANEOUS \- Phenotypic variability \- Based on report of 2 unrelated patients (last curated August 2018) MOLECULAR BASIS \- Caused by mutation in the member 1, family M, pleckstrin homology domain-containing protein gene (PLEKHM1, 611466.0002 ) ▲ 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
|
OSTEOPETROSIS, AUTOSOMAL DOMINANT 3
|
None
| 7,595 |
omim
|
https://www.omim.org/entry/618107
| 2019-09-22T15:43:37 |
{"omim": ["618107"]}
|
A number sign (#) is used with this entry because of evidence that neurodevelopmental disorder with ataxia, hypotonia, and microcephaly (NEDAHM) is caused by homozygous mutation in the SVBP gene (617853) on chromosome 1p34.
Clinical Features
Iqbal et al. (2019) reported 4 patients from 2 unrelated families with a similar neurodevelopmental disorder. The first family was a consanguineous Syrian family with 2 sibs aged 5 years and 13 months, and the second family was a consanguineous Pakistani family with 2 sibs aged 32 and 29 years. All had hypotonia, moderately to severely impaired intellectual development, short stature (range -2 to -3.9 SD), and microcephaly (-2.63 to -6.43 SD). The 3 patients who could walk had mildly delayed walking by age 3 and an ataxic gait. More variable features included abnormal chest shape and aggressive behavior (in the adult patients).
Inheritance
The transmission pattern of NEDAHM in the families reported by Iqbal et al. (2019) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 patients from 2 unrelated highly consanguineous families with NEDAHM, Iqbal et al. (2019) identified a homozygous nonsense mutation in the SVBP gene (Q28X; 617853.0001). The mutation, which was found by a combination of linkage analysis and exome or next generation sequencing of candidate genes and confirmed by Sanger sequencing, segregated with the disorder in both families. It was not found in the 1000 Genomes Project or gnomAD database, or in in-house ethnically matched controls. One family was of Syrian descent and the other of Pakistani descent; haplotype analysis indicated a founder effect. Analysis of patient cells showed no significant reduction in SVBP mRNA, but transfection of the mutation into HEK293 cells showed no evidence of a truncated protein by Western blot analysis, suggesting that the mutant mRNA or protein is rapidly degraded and results in a loss of function. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls. The authors concluded that SVBP plays a role in proper synapse formation and that loss of this function may contribute to neurodevelopmental abnormalities.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Poor overall growth HEAD & NECK Head \- Microcephaly (-2.6 to -6.4) CHEST External Features \- Abnormal chest shape \- Pectus excavatum MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired intellectual development \- Delayed walking, mild \- Ataxia Behavioral Psychiatric Manifestations \- Aggressive behavior MISCELLANEOUS \- Two unrelated consanguineous families have been reported (last curated September 2019) MOLECULAR BASIS \- Caused by mutation in the small vasohibin-binding protein (SVBP, 617853.0001 ) ▲ 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
|
NEURODEVELOPMENTAL DISORDER WITH ATAXIA, HYPOTONIA, AND MICROCEPHALY
|
None
| 7,596 |
omim
|
https://www.omim.org/entry/618569
| 2019-09-22T15:41:23 |
{"omim": ["618569"]}
|
Muscle phosphoglycerate mutase deficiency (PGAMD) is a metabolic myopathy characterised by exercise-induced cramp, myoglobinuria, and presence of tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels are increased between episodes of myoglobinuria. Less than 50 cases have been described so far. The disease is due to an anomaly in one of the last steps of glycolysis. The enzymatic defect in PGAMD is caused by mutations in the cDNA coding for the M-isoform of PGAM. Residual PGAM activity in the muscles of patients (2%-6%) is due to activity of the B-isoform. Transmission is autosomal recessive. Differential diagnosis includes muscle phosphorylase deficiency (McArdle disease) and phosphofructokinase deficiency (PFKD) (see these terms).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Glycogen storage disease due to phosphoglycerate mutase deficiency
|
c0268149
| 7,597 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97234
| 2021-01-23T18:31:30 |
{"gard": ["9964"], "mesh": ["C536176"], "omim": ["261670"], "umls": ["C0268149"], "icd-10": ["E74.0"], "synonyms": ["GSD due to phosphoglycerate mutase deficiency", "GSD type 10", "Glycogenosis due to phosphoglycerate mutase deficiency", "Muscle phosphoglycerate mutase deficiency", "Myopathy due to phosphoglycerate mutase deficiency"]}
|
Arterial dissection occurs when blood enters a vessel wall through an intimal tear and a false lumen is formed within the media. The arteries most commonly affected by dissection are the aorta, renal artery, and extracranial internal carotid artery, in that order of frequency. A genetic predisposition to arterial dissection is supported by its familial occurrence (see 147820; 607086; 122455) and its association with various heritable disorders of connective tissue, particularly the Marfan syndrome (154700).
Among approximately 240 patients with spontaneous cervical artery dissections seen in a 22-year period at the Mayo Clinic, Schievink et al. (1995) found 8 with a documented family history of arterial dissection. Two of these patients and their families represented instances of arterial dissection occurring at an early age and in association with multiple lentigines. Since the arterial media and melanocytes are derived from neural crest cells, Schievink et al. (1995) suggested that a neural crest defect may be the underlying abnormality in these families. The familial syndrome of arterial dissections with lentiginosis may represent an autosomal recessive disorder since 2 brothers were affected in 1 family and a brother and sister in another, the latter sibs being the progeny of parents related as half third cousins. In 1 family, a brother died suddenly of aortic dissection with rupture of the ascending aorta into the pericardium. Extensive cystic medial necrosis of the aorta was noted. His brother had surgical repair of aortic coarctation just distal to the left subclavian artery at the age of 19 years. At the age of 33 years, he suffered a left parietal lobe infarct, and stenosis due to dissection in the left internal carotid artery was demonstrated by cerebral angiography. Both brothers had numerous hyperpigmented skin lesions, mainly affecting the skin of the extremities, which were demonstrated to represent lentigines. They were of uniform size (approximately 3 mm in diameter) and dark brown to black. Some were present on the trunk and they were also found on the palms and soles. The face and mucous membranes were not involved. The skin lesions developed around the age of 2 years and increased markedly in number during adolescence. The other family was ascertained through a 24-year-old woman who, shortly after a downhill skiing accident, suffered dissection of the left cervical vertebral artery with resulting right hemiparesis and left Horner syndrome (143000). Six and one-half years later, 6 weeks postpartum, she had a sudden right occipital headache while breastfeeding. At the age of 25 years, 1 of her brothers developed a severe headache followed by right hemiparesis. There was no history of preceding trauma. Angiography revealed an area of smooth stenosis of the left extracranial internal carotid artery consistent with dissection. Both the brother and the sister had multiple skin lesions on the trunk and extremities, especially the lower legs. None of these patients had cafe-au-lait spots, ocular hypertelorism or deafness, and all were of normal stature.
The father in the second family reported by Schievink et al. (1995) had developed left hemiparesis at the age of 43 years and died suddenly 2 years later. Medical records were not available. He had no hyperpigmented skin lesions.
Lentigines are distinguished from freckles (ephelides) by their darker color, their presence in areas not exposed to the sun, the fact that they do not darken appreciably or increase in number during exposure to sun, and their relative uncommonness in red-haired and fair-skinned people. Histologically, lentigines have an increased number of melanocytes at the dermoepidermal junction and elongation of the rete ridges, whereas freckles have a normal or slightly decreased number of melanocytes and no elongation of the rete ridges. Lentiginosis is a component of Carney complex (160980) and of the LEOPARD syndrome (151100), but the other features of those syndromes indicate their distinctness from the new one described by Schievink et al. (1995). In the arterial segments available for study in both families, cystic medial necrosis was detected by microscopic examination.
Inheritance \- ? Autosomal recessive Skin \- Multiple lentigines Misc \- Aorta, renal artery, and extracranial internal carotid artery most commonly affected Lab \- Arterial cystic medial necrosis Vascular \- Arterial dissection ▲ 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
|
ARTERIAL DISSECTION WITH LENTIGINOSIS
|
c1838122
| 7,598 |
omim
|
https://www.omim.org/entry/600459
| 2019-09-22T16:16:12 |
{"mesh": ["C563937"], "omim": ["600459"], "orphanet": ["1682"]}
|
A number sign (#) is used with this entry because Temtamy syndrome (TEMTYS) is caused by homozygous or compound heterozygous mutation in the C12ORF57 gene (615140) on chromosome 12p13.
Description
Temtamy syndrome is a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus (summary by Akizu et al., 2013).
Clinical Features
Among the 6 children of a first-cousin marriage, Temtamy et al. (1991) observed a boy and 2 girls with a syndrome consisting of craniofacial dysmorphism, absent corpus callosum, and iris coloboma. Two of the 3 sibs had aortic dilatation with aortic regurgitation, and one had moderate mental retardation. The craniofacial anomalies consisted of macrodolichocephaly, arched eyebrows, antimongoloid slant of the eyes, beaked nose, low-set and simple lop ears, long philtrum, short upper lip, and micrognathia. In conjunction with the 'keyhole' coloboma of the iris, retina, and choroid, the lenses were dislocated upward and there was myopia and hypertelorism. Electron microscopy of the gingiva showed widening of the intercellular space, thickness of collagen fibers, and lack of periodicity. The sister, who died at age 22 years from heart failure, had moderate dilatation of the aorta, myocardial impairment, and bulbous thumbs. The affected male and his father had a satellited long arm of the Y chromosome (Yq). Temtamy et al. (1996) provided a full report of these 3 sibs. Photographs and comparisons with autosomal recessive and autosomal dominant disorders with iris coloboma and associated anomalies were provided.
Chan et al. (2000) described a male infant, born of nonconsanguineous parents, with right-sided iris coloboma and agenesis of the corpus callosum. Ophthalmologic examination revealed a very large chorioretinal coloboma involving the macula and optic nerve in the right eye in addition to the iris coloboma, and ultrasound and CT scan of the brain showed an absent corpus callosum. Developmental milestones were mildly delayed. Clinical manifestations shared by this case and the 3 children described by Temtamy et al. (1991) included agenesis of the corpus callosum, ocular coloboma, hypertelorism, frontal bossing, downslanting palpebral fissures, and micrognathia. Regarding their patient's relative macrocephaly, Chan et al. (2000) pointed out that, using the Nellhaus head circumference chart, 2 of the 3 previously reported cases also had relative macrocephaly rather than macrodolichocephaly. Chan et al. (2000) concluded that the primary clinical manifestations of the newly described syndrome include agenesis of the corpus callosum, ocular coloboma, hypertelorism, and relative macrocephaly.
Li et al. (2007) reported a brother and sister, born of consanguineous parents of Middle Eastern origin, with partial and complete agenesis of the corpus callosum, respectively, as well as colpocephaly and Probst bundles, optic coloboma, craniofacial dysmorphism, and skeletal anomalies. Li et al. (2007) noted that the sibs differed from the patients originally described by Temtamy et al. (1991) in that neither had cardiac anomalies, and both had severe mental retardation, intractable seizures, and interhemispheric colloid cyst, suggesting a more severe disruption of brain development. Linkage analysis did not identify a candidate disease locus.
Zahrani et al. (2013) reported a consanguineous Saudi Arabian family in which 4 sibs, ranging in age from 2.5 years to 19 years, had global developmental delay and early-onset refractory seizures. Two of the patients had colobomatous microphthalmia. Three had corpus callosum abnormalities: 1 with hyperplasia of the corpus callosum and 2 with agenesis of the corpus callosum. Another Saudi girl who belonged to the same tribe had profound global developmental delay, seizures, microphthalmia and coloboma involving the iris, choroid, and retina and extending to the optic cup. Her brain MRI was normal.
Akizu et al. (2013) reported 10 patients from 4 consanguineous families with Temtamy syndrome who were ascertained from a large cohort of families with corpus callosum hypoplasia. The families were from Kuwait, eastern Libya, and the United Arab Emirates; the fourth family was of Palestinian origin and had previously been reported by Li et al. (2007). The phenotype included hypotonia and moderate to severe intellectual disability with features of autism. Eight patients had epilepsy, 7 had dysmorphic craniofacial features, 5 had spasticity, and 4 had variable eye abnormalities, including esotropia and optic atrophy. One patient had microphthalmia and coloboma. Eight patients had brain imaging, which showed absent corpus callosum or hypoplasia of the corpus callosum, thalamic hypoplasia, and reduced white matter. Other more variable imaging findings included decreased anterior commissure, enlarged ventricles, and abnormal septum pellucidum.
Salih et al. (2013) reported a consanguineous Saudi Arabian family in which 4 of 6 sibs had features consistent with Temtamy syndrome, including developmental abnormalities of the brain and eyes. All 4 affected children had delayed motor and cognitive development with seizures in early childhood. The 3 older children had progressive, severe cognitive decline with spasticity beginning at age 3 to 5 years; decline was not seen in the youngest child, who was last examined at age 2 years. The 3 older children had progressive visual impairment; the youngest had grossly normal visual function but demonstrated oculodigital signs, which might be an early sign of visual impairment. On ophthalmologic examination, iris and chorioretinal colobomas, posterior staphyloma, microcornea with corneal opacity and dense cataract, and congenital nystagmus was seen in 1 child, and chorioretinal coloboma and posterior staphyloma was seen in another. The eyes of the 2 youngest affected sibs were normal on ophthalmologic examination. Magnetic resonance imaging of the brain was abnormal with agenesis, thickening, or dysgenesis of the corpus callosum seen in 3 of the 4 children.
Platzer et al. (2014) reported 2 sibs, born of unrelated German parents, with global developmental delay, severe intellectual disability, lack of speech acquisition, early-onset intractable seizures, and visual impairment. One child had bilateral chorioretinal coloboma and the other had an atrial septal defect. Additional findings in both children included nonspecific dysmorphic facial features, hypoplasia of the corpus callosum, short stature, and ataxic gait.
Inheritance
The transmission pattern of Temtamy syndrome in the families reported by Zahrani et al. (2013), Akizu et al. (2013), and Salih et al. (2013) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 Saudi Arabian sibs with mental retardation, early-onset seizures, and variable coloboma and corpus callosum abnormalities, Zahrani et al. (2013) identified a homozygous mutation in the C12ORF57 gene (c.1A-G; 615140.0001). The mutation was identified by exome sequencing of 1 of the patients. An unrelated Saudi girl with a similar disorder was compound heterozygous for the 1A-G mutation and another C12ORF57 mutation (L51Q; 615140.0002). In 10 patients from 4 consanguineous families of Arab descent with a phenotype consistent with Temtamy syndrome, including the family reported by Li et al. (2007), Akizu et al. (2013) identified homozygosity for the same 1A-G mutation in C12ORF57. The mutation was found by whole-exome sequencing, confirmed by Sanger sequencing, and coincided with linkage data. All tested parents were heterozygous for the mutation, which was not found in more than 1,400 individuals, including 1,000 of Arab descent, or in public SNP databases. Haplotype analysis was consistent with a founder effect. In vitro cellular expression studies indicated that the mutation decreased protein synthesis, but some protein could be formed, likely resulting in phenotypic variability. These findings suggested a loss-of-function mechanism.
In 4 sibs, born to second-cousin Saudi Arabian parents, with Temtamy syndrome, Salih et al. (2013) found homozygosity for the c.1A-G mutation in the C12ORF57 gene (M1V; 615140.0001). The parents were heterozygous for the mutation, which was not found in 1 unaffected sib or in more than 350 normal individuals. Salih et al. (2013) noted that Najmabadi et al. (2011) had previously identified M1V as a possible causative mutation for nonsyndromic mental retardation in this family (G001).
In 2 sibs, born of unrelated German parents, with Temtamy syndrome, Platzer et al. (2014) identified compound heterozygous mutations in the C12ORF57 gene: the recurrent c.1A-G transition and a novel nonsense mutation (Q62X; 615140.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family.
History
Talisetti et al. (2003) described a 5-year-old girl who had features resembling Temtamy syndrome, including agenesis of the corpus callosum, ventriculomegaly, frontal bossing, peaked eyebrows, ptosis, malformed and low-set ears, depressed nasal bridge, long philtrum, and iris and chorioretinal colobomas. Features unique to this child included profound mental retardation, bilateral sensorineural hearing loss, patent ductus arteriosus, ventricular septal defect, unilateral renal agenesis, neurogenic bladder, and hydronephrosis. The patient was found to have a de novo balanced translocation t(2;9)(p24;q32); Talisetti et al. (2003) noted that there was phenotypic overlap with monosomy for chromosome 2p. Ramocki et al. (2003) analyzed the breakpoints in the patient reported by Talisetti et al. (2003) using FISH and PCR analysis and identified disruption of 2 zinc finger-encoding transcripts, KIAA1803 (ZNF462; 617371) on chromosome 9 and ASXL2 (612991) on chromosome 2.
In a consanguineous family of Middle Eastern origin with a Temtamy-like syndrome, Li et al. (2007) performed homozygosity mapping for the ASXL2 and ZNF462 genes, as well as for VAX1 (604294), a gene known to cause agenesis of the corpus callosum when its homolog is inactivated in mice; however, at no locus were the 2 affected sibs homozygous, while the 3 healthy sibs were either heterozygous or homozygous for a different allele, thus excluding the possibility that a recessive allele for the syndrome lies at 1 of these 3 loci.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Long face \- Micrognathia \- Frontal bossing \- Long philtrum Ears \- Low-set ears \- Simple ears \- Lop ears Eyes \- Hypertelorism \- 'Key-hole' iris, retina, choroid coloboma \- Myopia \- Dislocated lens (upward) \- Downslanting palpebral fissures \- Arched eyebrows Nose \- Beaked nose Teeth \- Dental crowding \- Hypoplastic teeth SKELETAL Pelvis \- Hip dislocation Limbs \- Genua valgum Hands \- Brachydactyly (2nd-5th fingers) \- Bulbous thumbs Feet \- Brachydactyly (2nd-5th toes) \- Pes planus \- Talipes equinovarus NEUROLOGIC Central Nervous System \- Global developmental delay \- Mental retardation \- Hypotonia \- Seizures, early-onset \- Corpus callosum abnormalities \- Agenesis of the corpus callosum \- Reduced white matter \- Thalamic hypoplasia \- Enlarged ventricles \- Abnormal septum pellucidum Behavioral Psychiatric Manifestations \- Autistic features MISCELLANEOUS \- Onset in infancy \- Skeletal and facial features are variable MOLECULAR BASIS \- Caused by mutation in the chromosome 12 open reading frame 57 gene (C12ORF57, 615140.0001 ) ▲ 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
|
TEMTAMY SYNDROME
|
c1857512
| 7,599 |
omim
|
https://www.omim.org/entry/218340
| 2019-09-22T16:29:17 |
{"mesh": ["C536959"], "omim": ["218340"], "orphanet": ["1777"], "synonyms": ["Alternative titles", "MENTAL RETARDATION WITH OR WITHOUT CRANIOFACIAL DYSMORPHISM, OCULAR COLOBOMA, OR ABNORMAL CORPUS CALLOSUM"]}
|
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