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## Summary
### Clinical characteristics.
ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), spans a phenotypic spectrum that includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end. Affected individuals have furrowing of the skin of the whole body that improves with time. They may have other evidence of a generalized connective disorder, including enlarged anterior fontanelle in infancy, congenital dislocation of the hips, inguinal hernias, and high myopia. In most (not all) affected individuals, cortical and cerebellar malformations are present and are associated with severe developmental delays, seizures, and neurologic regression.
### Diagnosis/testing.
Diagnosis is based on characteristic findings on clinical examination of the skin, serum sialotransferrin isoelectric focusing (IEF), serum apolipoprotein C III IEF, and molecular genetic testing of ATP6V0A2, the only gene known to be associated with this disorder.
### Management.
Treatment of manifestations: Antiepileptic drugs (AEDs), repair of inguinal hernia(s), routine management of hip dislocation, and psychological help as needed for self-image issues.
Prevention of secondary complications: Treatment for bleeding disorder linked to coagulation factor deficiencies to prevent anemia.
Surveillance: Annual ophthalmologic examination.
Other: Plastic surgery in infancy or childhood is not advised, as the skin findings tend to improve with age.
### Genetic counseling.
ATP6V0A2-related cutis laxa is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants have been identified in the family.
## Diagnosis
### Suggestive Findings
Diagnosis of ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A) should be suspected in individuals with the following findings.
Characteristic signs of cutis laxa
* Furrowing of the skin of the whole body; particularly obvious in neck, axillae, and groin
* Droopy skin on the cheeks of the face and marked nasolabial folds, giving rise to distinctive facial features that also include prominent large nasal root, downslanted palpebral fissures, and delayed closure of the fontanelles
* Skin that when extended does not display marked hyperelasticity (as is observed in the Ehlers-Danlos syndromes) but rather maintains its consistency
Other evidence of a generalized connective tissue disorder
* Enlarged fontanelles (i.e., delayed closure of the fontanelles) manifest in newborns (anterior fontanelle >6x6 cm in the newborn; >3x3 cm at age one year)
* Congenital dislocation of the hips
* Inguinal hernias
* High myopia
* Bruch’s membrane rupture
Central nervous system (CNS) abnormalities. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI.
* Cortical malformation. Abnormally thick (5-10 mm) cortex has subtle vertical streaks that appear smooth in some areas and irregular in others, resembling either lissencephaly or polymicrogyria, particularly the cortical malformation of ADGRG1-associated fronto-parietal cobblestone-like cortical malformation (see Polymicrogyria Overview) or muscle-eye-brain (MEB) disease, except that white matter changes are more prominent in the two latter conditions.
This cortical malformation differs from lissencephaly and polymicrogyria by a consistent and predominant bilateral, symmetric, and frontal distribution that is more severe in the posterior portion of the frontal lobe and the anterior portion of the parietal lobes (including the perisylvian cortex) and less severe in the anterior portion of the frontal lobe and often the superior portion of the temporal lobe. No well-defined microgyri are seen, which also distinguishes the disorder from true polymicrogyria.
* Cerebellar malformation ranges from mild cerebellar vermis hypoplasia to classic Dandy-Walker malformation, including severe hypoplasia and upward rotation of the vermis, cystic enlargement of the fourth ventricle, and enlarged posterior fossa.
* Corpus callosum is normal, in contrast to PYCR1-related cutis laxa, as underlined recently by a Dutch group [Gardeitchik et al 2014].
Laboratory test and skin biopsy findings
Serum sialotransferrin isoelectric focusing (IEF) reveals the following findings in ATP6V0A2-related cutis laxa:
* Reduction of the main protein band, which corresponds to transferrin containing four sialic acid residues
* Increased amounts of disialo- and trisialo-transferrin that indicate altered N-glycosylation over the normal ranges of:
* Disialotransferrin: 2.5%-9.8%
* Trisialotransferrin: 3.4%-13.7%
These findings, which are also observed in type 2 congenital disorder of glycosylation (CDG type 2), support the diagnosis of ATP6V0A2-related cutis laxa [Morava et al 2005, Wopereis et al 2005, Morava et al 2008, Guillard et al 2009] (see Congenital Disorders of Glycosylation Overview).
Note: In the authors' experience, all probands had a CDG type 2 sialotransferrin IEF pattern; however, it has been observed that infants may have a normal transferrin isofocusing profile in the first months of life, but develop the typical transferrin abnormality later on. In these infants, the apolipoprotein C-III isofocusing was already abnormal in the first months of life [Morava et al 2005, Wopereis et al 2005].
Serum apolipoprotein C III isoelectric focusing (IEF) reveals the following changes of altered O-glycosylation:
* Reduction of the main protein band, which corresponds to apolipoprotein CIII containing two sialic acid residues
* Increased amounts of monosialotransferrin. Normal ranges depend on age. In adults: monosialotransferrin: 43%-69%; disialotransferrin: 23%-50%.
Abnormal O-glycosylation is supportive of the diagnosis, but a normal or inconclusive result does not eliminate the possibility of ATP6V0A2-related cutis laxa. In the authors' experience, comparing the findings in the parents with those of the index case is most helpful in identifying the reduction of the main band.
Skin biopsy with orcein staining
* Light microscopy is normal.
* Electron microscopy (EM) shows rarefaction and fragmentation of the elastin network in which elastic fibers are small and misshapen. Within these fibers both elastin and elastofibrils can be distinguished based on their different densities.
Note: EM studies require a high level of expertise and are only available in specialized centers.
* The EM findings strongly support the diagnosis of ATP6V0A2-related cutis laxa but are also seen in De Barsy syndrome [Guerra et al 2004] (see Differential Diagnosis).
* EM findings differ from the misassembly of elastin fibers observed in FBLN5-associated cutis laxa.
### Establishing the Diagnosis
The diagnosis of ATP6V0A2-related cutis laxa is established in a proband with the identification of biallelic pathogenic variants in ATP6V0A2 (see Table 1). Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing.
* Single-gene testing. Sequence analysis of ATP6V0A2 is performed first and followed by deletion/duplication analysis if only one or no pathogenic variant is found.
* Use of a multigene panel that includes ATP6V0A2 and other genes of interest (see Differential Diagnosis) may also be used. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing (and/or use of a multigene panel that includes ATP6V0A2) has not confirmed a diagnosis in an individual with features of ATP6V0A2-related cutis laxa. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in ATP6V0A2-Related Cutis Laxa
View in own window
Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
ATP6V0A2Sequence analysis 2>95% 3
Deletion/duplication analysis 4Unknown 5
1\.
See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
2\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
3\.
Thus far diagnosis of ATP6V0A2-related cutis laxa has been confirmed in more than 61 individuals by ATP6V0A2 sequencing. In individuals with cutis laxa and a clear CDG type 2 sialotransferrin IEF pattern, variant detection rate exceeds 95% [Gardeitchik et al 2014].
4\.
Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
5\.
Hucthagowder et al [2009] identified deletion of exon 16 in four unrelated individuals of Middle Eastern origin in their cohort of 17 affected individuals from 16 families.
## Clinical Characteristics
### Clinical Description
ATP6V0A2-related cutis laxa spans a phenotypic spectrum that includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end; these two phenotypes were thought to be distinct clinical entities until their molecular genetic nature was determined. Children with Debré-type cutis laxa have more severe developmental and neurologic abnormalities and a less severe cutaneous phenotype than children with wrinkly skin syndrome.
At birth, hypotonia, over-folded skin, and distinctive facial features are present. Enlarged fontanelles are invariably present in infants with Debré-type cutis laxa. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. In ATP6V0A2-related cutis laxa the skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some [Greally et al 2014].
Developmental delay. Nearly all affected children described to date have had delayed developmental milestones and intellectual disability. Most have borderline microcephaly with head circumference in the range of 2-3 standard deviations below the mean. Despite delays in developmental milestones and language, affected children are said to be cheerful and outgoing.
Neurologic findings
* Cognitive. Many children have a degenerative course including cognitive decline that begins about the end of the first decade.
* Seizures. Generalized or partial complex seizures begin between ages eight and 12 years. Six of eight children fulfilling diagnostic criteria for Debré-type cutis laxa developed seizures by their mid-teens.
Note: By contrast, a lower rate of seizures was observed in two cohorts: one of children with ATP6V0A2-related cutis laxa (regardless of accompanying signs and symptoms) and abnormal IEF [Morava et al 2005, Morava et al 2008]; and the other of children from Oman [Rajab et al 2008]. An explanation could be age-related bias of ascertainment, given that most children in these two cohorts were young.
* Neurologic regression (with or without seizures) can include spasticity and cerebellar signs and symptoms (ataxia, slurred speech). Some adolescents become wheelchair bound. A unique individual with mild brain dysgenesis and compound heterozygosity for ATP6V0A2 pathogenic variants had a normal IQ with no history of seizures, and was doing well in mainstream school at age 15 years [Van Maldergem et al 2008].
Ophthalmologic concerns. High myopia (> -5 diopters) has been observed in the majority of affected individuals. One Portuguese individual had an unclassified corneal dysplasia requiring engraftment; a Belgian individual had unilateral rupture of Bruch's membrane rupture. Strabismus has been observed in nearly half of patients.
Other
* Pulmonary emphysema does not occur.
* Bleeding disorder linked to coagulation factor deficiencies may occur.
Wrinkly skin syndrome (WSS) includes many features of Debré-type cutis laxa but is milder [Gazit et al 1973]. Usually, affected individuals have only mild developmental delay without subsequent neurodegeneration. The skin shows tighter wrinkles and the changes in facial features are milder [Al-Gazali et al 2001]. In one of the four families with WSS from Oman described recently, the father of an index patient appeared to be affected as well, as determined by molecular genetic testing after subtle signs of WSS were noted during clinical examination [Rajab et al 2008].
### Genotype-Phenotype Correlations
No genotype-phenotype correlations are known.
### Prevalence
The prevalence of all types of cutis laxa is 1:4,000,000 according to Rhône-Alpes Eurocat registry [E Robert, personal observation].
## Differential Diagnosis
Other disorders characterized by cutis laxa are summarized in Table 2.
FBLN5-related cutis laxa (ARCL1A; ADCL2) is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow viscus diverticula (e.g., intestine, bladder). Occasionally, supravalvular aortic stenosis is observed. Intrafamilial variability in age of onset is observed. Cardiorespiratory failure from complications of pulmonary emphysema (respiratory or cardiac insufficiency) is the most common cause of death. Inheritance is usually autosomal recessive; autosomal dominant inheritance is possible.
EFEMP2-related cutis laxa (ARCL1B) is characterized by cutis laxa and systemic involvement, most commonly arterial tortuosity, aneurysms and stenosis; retrognathia; joint laxity; and arachnodactyly. Severity ranges from perinatal lethality as a result of cardiopulmonary failure to manifestations limited to the vascular and craniofacial systems. Inheritance is autosomal recessive.
The cutis laxa and emphysema are similar in EFEMP2\- or FBLN5-related cutis laxa; however, to date the diaphragmatic changes and arterial aneurysms appear to be more predominant in EFEMP2-related cutis laxa.
ELN-related cutis laxa (ADCL1) (OMIM 123700) was historically considered a strictly cutaneous disorder without systemic involvement; however, it is now known that persons with ELN pathogenic variants can also have aortic aneurysms that require aortic root replacement or lead to aortic rupture in early adulthood. The aortic pathology of these aneurysms is indistinguishable from that of Marfan syndrome. It remains to be seen whether ELN is mutated in persons with thoracic aortic aneurysms and aortic dissections (TAAD) [Urban et al 2005]. Inheritance is autosomal dominant.
Gerodermia osteodysplastica (GO) (OMIM 231070). Onset occurs in infancy or early childhood; for review, see Nanda et al [2008]. Children appear older than their age because of sagging cheeks and jaw hypoplasia. Skin wrinkling is less severe and is confined to the dorsum of the hands and feet and to the abdomen when in the sitting position. A generalized connective tissue weakness leads to frequent hip dislocation and hernias; however, GO can be distinguished from other types of cutis laxa by the presence of osteopenia/osteoporosis and fractures, most commonly vertebral compression fractures, but also fractures of the long bones. Mental development is in the normal range. In contrast to Debré-type cutis laxa, fontanelle size and closure are normal; positioning of the palpebral fissures is normal; and disease manifestations do not become milder with age. Pathogenic variants in GORAB (formerly SCYL1BP1) are causative [Hennies et al 2008]. Inheritance is autosomal recessive. A GO-like phenotype, but in most cases with intellectual disability, can be caused by pathogenic variants in PYCR1 (see below).
De Barsy syndrome B (ARCL3B) (OMIM 614438) is characterized by a progeroid appearance, pre- and postnatal growth retardation, moderate to severe intellectual disability, corneal clouding or cataracts, and generalized cutis laxa [Guerra et al 2004]. The progeroid appearance is not caused by skin sagging, but rather by a hypoplasia of the dermis. Joint hyperlaxity, pseudo-athetoid movements, and hyperreflexia are observed. Inheritance is autosomal recessive. In a number of individuals who received this diagnosis, pathogenic variants in PYCR1 were identified [Reversade et al 2009] (see following).
PYCR1-related cutis laxa (ARCL2B; ARCL3B) (OMIM 612940, 614438). Pathogenic variants in PYCR1 cause a phenotype which shares many similarities with GO, wrinkly skin syndrome, and De Barsy syndrome. Affected individuals have a common facial gestalt with triangular face, hypomimia, large everted ears, and a cutis laxa more pronounced in extremities. About 95% of affected individuals have intellectual disability. Hypoplasia of the corpus callosum is common. The protein is involved in proline biosynthesis in mitochondria [Reversade et al 2009]. Inheritance is autosomal recessive.
ALDH18A1-related cutis laxa (ARCL3A) (OMIM 219150). A syndrome of IUGR, cataracts, postnatal growth failure and developmental delay with cutis laxa has been described in two pedigrees. Joint hyperlaxity is apparently a common feature. This syndrome falls within de Barsy syndrome spectrum. It is associated with pathogenic variants in ALDH18A1, previously known as P5CS, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS) [Baumgartner et al 2000, Baumgartner et al 2005, Bicknell et al 2008]. Inheritance is autosomal recessive.
LTBP4-related cutis laxa (ARCL1C). Urban et al [2009] described four patients with a phenotype resembling pulmonary-associated cutis laxa (EFEMP2- and FBLN5-related). A characteristic of this subtype is the severity of associated malformations, including major congenital heart disease, severe pulmonary hypertension, thought to be the consequence of pulmonary arterial stenosis. Diaphragmatic hernia and multiple bladder diverticulae with vesicoureteral reflux were causative of life-threatening complications and short life span. The authors observed prolonged survival in a girl who ultimately died of multiple brain abscesses at age 14 years.
A droopy facial appearance is very similar to that seen in EFEMP2\- and FBLN5-related CL.
LTBP4 encodes a protein which plays a role in assembly of elastin fibers. Inheritance is autosomal recessive [Callewaert et al 2013].
RIN2-related cutis laxa. Pathogenic variants in RIN2 cause MACS syndrome (OMIM 613075) (macrocephaly, alopecia, cutis laxa, scoliosis), displaying a very characteristic facial gestalt [Basel-Vanagaite et al 2009]. Cutis laxa is mild and mostly manifests as redundant facial skin. Mild intellectual disability is only present in some affected individuals. Inheritance is autosomal recessive.
Arterial tortuosity syndrome (ATS) is characterized by severe and widespread arterial tortuosity of the aorta and middle-sized arteries (with an increased risk of aneurysms and dissections) and focal and widespread stenosis which can involve the aorta and/or pulmonary arteries. The vascular findings occur in combination with soft/doughy skin and other evidence of a generalized connective tissue disorder including skeletal findings (scoliosis, pectus excavatum/carinatum, joint laxity, knee/elbow contractures, arachnodactyly, camptodactyly), inguinal/abdominal wall hernia, sliding hiatal or diaphragmatic hernia, hypotonia, and ocular involvement (myopia, keratoconus). Individuals may display a droopy facial appearance similar to that observed in other forms of cutis laxa [Karakurt et al 2012] and have a high palate with dental crowding.
Pathogenic variants in SLC2A10 are causative. Inheritance is autosomal recessive.
Lenz-Majewski syndrome (LMS) (OMIM 151050). Individuals with LMS display early cutis laxa followed by progressive thinning of the skin with prominent veins. Severe brachydactyly and a unique facial appearance with prominent eyes distinguish LMS in the early stages from other forms of cutis laxa [Sousa et al 2014]. The clinical course usually includes profound intellectual disability, very short stature, and progressive hyperostosis. Heterozygous pathogenic variants in PTDSS1 are causative. Inheritance is autosomal dominant.
### Table 2.
Disorders to Consider in the Differential Diagnosis of Cutis Laxa
View in own window
Disease NameGeneOMIMMOIClinical Findings
Cutis laxaEmphysemaAneurysmsDDBladder
diverticulae
ALDH18A1–related cutis laxaALDH18A1219150AR+--++-
FBLN5-related cutis laxaFBLN5219100AR++++++--++
EFEMP2-related cutis laxaEFEMP2 (FBLN4)614437AR+++++++--
ARCL2AATP6V0A2219200
278250AR++--++-
ADCL1 or ADCL2ELN or FBLN5123700
614434AD+++--
GOGORAB231070AR++----
De Barsy syndrome BPYCR1614438AR+--+++-
ARCL2BPYCR1612940AR+--+++-
LTBP4-related cutis laxaLTBP4613177AR+++++++
RIN2-related cutis laxaRIN2613075AR+--+/-Unknown
ATSSLC2A10208050AR+-++-Unknown
LMSPTDSS1151050AD+--+++Unknown
ADCL = autosomal dominant cutis laxa; ARCL2A = the subject of this GeneReview; ARCL2B = PYCR1-related cutis laxa; ATS = arterial tortuosity syndrome; DD = developmental delay; GO = gerodermia osteodysplastica; LMS = Lenz-Majewski syndrome; MOI = mode of inheritance
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with ATP6V0A2-related cutis laxa, the following evaluations are recommended:
* Ortolani sign for detection of hip dislocation. Hip ultrasound examination as needed based on clinical findings.
* Pelvic x-ray (1x only) to identify hip dysplasia in the event that hip dislocation has not been treated properly.
* Assessment for inguinal hernias
* Ophthalmologic examination, including refraction (for myopia), slit-lamp examination, fundus examination. Note: Slit-lamp examination allows diagnosis of corneal dysplasia, which was present in one individual.
* Baseline neurodevelopmental evaluation
* Brain MRI
* EEG if seizures are suspected
* Echocardiogram to look for evidence of floppy valves or more severe valvular dysplasia that can often be observed in a connective tissue disorder
* Evaluation for a bleeding disorder linked to coagulation factor deficiencies
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
The following are appropriate:
* Repair of inguinal hernia(s)
* Routine management of hip dislocation
* Routine management of refractive errors
* Early education services and developmental therapies with later special education supports
* Antiepileptic drugs (AEDs): valproate. Because treatment with valproate is often unsuccessful, carbamazepine can serve as a second-line drug and levetiracetam as a third-line drug; or a combination of AEDs can be used.
* Psychological help as needed for self-image issues
### Prevention of Secondary Complications
Treat for bleeding disorder linked to coagulation factor deficiency to prevent anemia.
### Surveillance
Perform annual ophthalmologic examination, including refraction for evidence of myopia (which can be progressive) and fundus examination to inspect Bruch's membrane.
### Evaluation of Relatives at Risk
It is appropriate to test older and younger sibs for presence of the ATP6V0A2 pathogenic variants found in the proband in order to identify as early as possible those who would benefit from institution of treatment and preventive measures.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ATP6V0A2-Related Cutis Laxa
|
None
| 8,200 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK5200/
| 2021-01-18T21:44:16 |
{"synonyms": ["Autosomal Recessive Cutis Laxa Type 2A (ARCL2A)"]}
|
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-65 (EIEE65) is caused by heterozygous mutation in the CYFIP2 gene (606323) on chromosome 5q33.
Description
Early infantile epileptic encephalopathy-65 is characterized by onset of intractable seizures of various types within 6 months of birth, severe to profound psychomotor developmental delay, and mild facial dysmorphism (summary by Nakashima et al., 2018).
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical Features
Nakashima et al. (2018) reported 4 unrelated boys, between 3 and 11 years of age, with EIEE. Two patients were of Japanese descent, 1 was Israeli, and 1 was Malaysian. In the first 6 months of life, the patients had onset of frequent and intractable seizures associated with multifocal spikes, sharp waves, spike and slow wave complexes, suppression-burst patterns, and/or hypsarrhythmia on EEG. Seizure types were variable, and included generalized tonic-clonic, focal, and myoclonic. All patients had profoundly delayed psychomotor development and were bedridden with hypotonia, spasticity, pyramidal signs, absent speech, and poor or absent interaction with others. Three patients developed progressive microcephaly (up to -5.1 SD), and 3 patients had mild nonspecific dysmorphic features, including arched eyebrows, swelling of the lips and gingiva, and tented mouth. One patient (patient 4) was seizure-free since age 3 years, but remained profoundly developmentally impaired and had no voluntary movement at age 5. Brain imaging in 3 patients showed progressive cerebral and cerebellar atrophy; 1 patient also had enlarged ventricles and a dysmorphic corpus callosum. Brain imaging in patient 4 was normal at age 8 months.
Molecular Genetics
In 4 unrelated boys with EIEE65, Nakashima et al. (2018) identified 3 different de novo heterozygous missense mutations in the CYFIP2 gene (606323.0001-606323.0003). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, all affected the same highly conserved residue (arg87) in the DUF1394 domain. Molecular modeling based on CYFIP1 predicted that mutations at arg87 may disrupt key hydrogen bonds and lead to structural instability, resulting in aberrant activation of the WAVE regulatory complex. Coimmunoprecipitation studies of lymphoblastoid cells derived from 1 patient showed that mutant CYFIP2 had weaker interaction with the VCA domain of the WAVE complex compared to controls, which may release suppression. Cells transfected with the mutation showed increased aberrant F-actin accumulation compared to controls, suggesting abnormal actin polymerization. Nakashima et al. (2018) concluded that the mutations occur at a hotspot and result in a gain-of-function effect on the WAVE signaling pathway. Dysregulation of actin dynamics could cause dendritic spine abnormalities that may disrupt the balance between brain excitation and inhibition. The patients were ascertained from a cohort of 699 individuals with early-onset epileptic encephalopathy who underwent whole-exome sequencing.
INHERITANCE \- Autosomal dominant GROWTH Other \- Poor overall growth HEAD & NECK Head \- Microcephaly, progressive Eyes \- Arched eyebrows Mouth \- Tented lip \- Thick lip \- Thick gums MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Seizures, multiple types \- Hypsarrhythmia seen on EEG \- Multifocal spikes, sharp waves \- Spike and slow wave complexes, Suppression-burst pattern \- Developmental delay, profound \- Inability to sit or walk \- Lack of voluntary movement \- Absent speech \- No communication \- Spasticity \- Hyperreflexia \- Brain imaging abnormalities (in most patients) \- Cerebral atrophy, progressive \- Cerebellar atrophy, progressive \- Enlarged ventricles \- Dysmorphic corpus callosum MISCELLANEOUS \- Onset of seizures in the first months of life \- Seizures are usually refractory to treatment \- Patients are bedridden \- De novo mutation \- Four unrelated patients have been reported (last curated June 2018) MOLECULAR BASIS \- Caused by mutation in the cytoplasmic FMRP-interacting protein 2 gene (CYFIP2, 606323.0001 ) ▲ 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
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 65
|
c4693925
| 8,201 |
omim
|
https://www.omim.org/entry/618008
| 2019-09-22T15:43:58 |
{"doid": ["0080430"], "omim": ["618008"], "orphanet": ["442835"], "synonyms": ["Undetermined EOEE"]}
|
A rare inflammatory and suppurating type of tinea capitis, a skin infection caused by Trichophyton or Microsporum fungi, that predominantly affects the scalp and that is characterized by the development of painful crusty lesions covered with follicular pustules and surrounded by erythematous alopecic areas, that can later evolve into abscesses and leave permanent cicatricial alopecia. Lesions can be associated with regional lymphadenopathy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Kerion celsi
|
c0276742
| 8,202 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=499
| 2021-01-23T18:29:50 |
{"gard": ["3109"], "mesh": ["D014006", "C536165"], "umls": ["C0276742"], "icd-10": ["B35.0"]}
|
A rare leukoencephalopathy characterized by acute episodes of neurological deficit (ataxia, dysarthria, seizures) with irritability and opisthotonus followed by either steady deterioration or alternating periods of rapid progression and prolonged periods of stability.
## Epidemiology
So far around 20 patients have been reported in the literature.
## Clinical description
Onset occurs in infancy or early childhood.
## Etiology
The etiology remains unknown.
## Diagnostic methods
MRI imaging reveals irregular asymmetric patches of leukoencephalopathy with cavities, vascular permeability and cystic degeneration affecting principally the corpus callosum, cerebral and cerebellar white matter, and spinal cord.
## Genetic counseling
The mode of transmission is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Progressive cavitating leukoencephalopathy
|
c4304840
| 8,203 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139447
| 2021-01-23T16:55:58 |
{"icd-10": ["E75.2"]}
|
Primary melanoma of the central nervous system is a rare tumor of meninges arising from leptomeningeal melanocytes, typically in the perimedullary or high cervical region, in the absence of melanoma outside the CNS. The tumor is typically a darkly pigmented, solid mass, often containing hemorrhagic or necrotic areas, composed of sheets of pleomorphic cells with prominent nucleoli, with frequent mitotic figures and parenchymal invasion. Intracranial tumor may present with signs of raised intracranial pressure, focal neurological symptoms related to tumor location, seizures or subarachnoid hemorrhage, spinal tumor may present with back pain, muscle weakness, numbness, plegia or urinary incontinence.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing 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 melanoma of the central nervous system
|
c0349626
| 8,204 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=252050
| 2021-01-23T18:17:41 |
{"gard": ["12016"], "synonyms": ["Malignant melanoma of meninges", "Primary melanoma of the CNS"]}
|
Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).
The heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.
People with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.
Complications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.
Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body).
## Frequency
Wolff-Parkinson-White syndrome affects 1 to 3 in 1,000 people worldwide.
Wolff-Parkinson-White syndrome is a common cause of an arrhythmia known as paroxysmal supraventricular tachycardia. Wolff-Parkinson-White syndrome is the most frequent cause of this abnormal heart rhythm in the Chinese population, where it is responsible for more than 70 percent of cases.
## Causes
In most cases, the cause of Wolff-Parkinson-White syndrome is unknown. A small percentage of all cases are caused by mutations in the PRKAG2 gene. Some people with these mutations also have features of hypertrophic cardiomyopathy, a form of heart disease that enlarges and weakens the heart (cardiac) muscle. The PRKAG2 gene provides instructions for making a protein that is part of an enzyme called AMP-activated protein kinase (AMPK). This enzyme helps sense and respond to energy demands within cells. It is likely involved in the development of the heart before birth, although its role in this process is unclear.
Researchers are uncertain how PRKAG2 gene mutations lead to the development of Wolff-Parkinson-White syndrome and related heart abnormalities. Research suggests that these mutations alter the activity of AMP-activated protein kinase in the heart, although it is unclear whether the genetic changes overactivate the enzyme or reduce its activity. Studies indicate that changes in AMP-activated protein kinase activity allow a complex sugar called glycogen to build up abnormally within cardiac muscle cells. Other studies have found that altered AMP-activated protein kinase activity is related to changes in the regulation of certain ion channels in the heart. These channels, which transport positively charged atoms (ions) into and out of cardiac muscle cells, play critical roles in maintaining the heart's normal rhythm.
### Learn more about the gene associated with Wolff-Parkinson-White syndrome
* PRKAG2
## Inheritance Pattern
Most cases of Wolff-Parkinson-White syndrome occur in people with no apparent family history of the condition. These cases are described as sporadic and are not inherited.
Familial Wolff-Parkinson-White syndrome accounts for only a small percentage of all cases of this condition. The familial form of the disorder typically has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, a person with familial Wolff-Parkinson-White syndrome has inherited the condition from an affected parent.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Wolff-Parkinson-White syndrome
|
c0043202
| 8,205 |
medlineplus
|
https://medlineplus.gov/genetics/condition/wolff-parkinson-white-syndrome/
| 2021-01-27T08:24:43 |
{"gard": ["7897"], "mesh": ["D014927"], "omim": ["194200"], "synonyms": []}
|
Patent urachus is a type of congenital urachal anomaly (see this term) characterized by a persistent communication between the bladder and the umbilicus, secondary to non occlusion of the urachal lumen, manifesting as clear drainage from the umbilicus.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Patent urachus
|
c0266357
| 8,206 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=431341
| 2021-01-23T17:22:42 |
{"icd-10": ["Q64.4"]}
|
Sick sinus syndrome (also known as sinus node dysfunction) is a group of related heart conditions that can affect how the heart beats. "Sick sinus" refers to the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally. In some cases, it does not produce the right signals to trigger a regular heartbeat. In others, abnormalities disrupt the electrical impulses and prevent them from reaching the rest of the heart.
Sick sinus syndrome tends to cause the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia). In some cases, the heartbeat rapidly switches from being too fast to being too slow, a condition known as tachycardia-bradycardia syndrome. Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue). Once symptoms of sick sinus syndrome appear, they usually worsen with time. However, some people with the condition never experience any related health problems.
Sick sinus syndrome occurs most commonly in older adults, although it can be diagnosed in people of any age. The condition increases the risk of several life-threatening problems involving the heart and blood vessels. These include a heart rhythm abnormality called atrial fibrillation, heart failure, cardiac arrest, and stroke.
## Frequency
Sick sinus syndrome accounts for 1 in 600 patients with heart disease who are over age 65. The incidence of this condition increases with age.
## Causes
Sick sinus syndrome can result from genetic or environmental factors. In many cases, the cause of the condition is unknown.
Genetic changes are an uncommon cause of sick sinus syndrome. Mutations in two genes, SCN5A and HCN4, have been found to cause the condition in a small number of families. These genes provide instructions for making proteins called ion channels that transport positively charged atoms (ions) into cardiac cells, including cells that make up the SA node. The flow of these ions is essential for creating the electrical impulses that start each heartbeat and coordinate contraction of the cardiac muscle. Mutations in these genes reduce the flow of ions, which alters the SA node's ability to create and spread electrical signals. These changes lead to abnormal heartbeats and the other symptoms of sick sinus syndrome.
A particular variation in another gene, MYH6, appears to increase the risk of developing sick sinus syndrome. The protein produced from the MYH6 gene forms part of a larger protein called myosin, which generates the mechanical force needed for cardiac muscle to contract. Researchers believe that the MYH6 gene variation changes the structure of myosin, which can affect cardiac muscle contraction and increase the likelihood of developing an abnormal heartbeat.
More commonly, sick sinus syndrome is caused by other factors that alter the structure or function of the SA node. These include a variety of heart conditions, other disorders such as muscular dystrophy, abnormal inflammation, or a shortage of oxygen (hypoxia). Certain medications, such as drugs given to treat abnormal heart rhythms or high blood pressure, can also disrupt SA node function. One of the most common causes of sick sinus syndrome in children is trauma to the SA node, such as damage that occurs during heart surgery.
In older adults, sick sinus syndrome is often associated with age-related changes in the heart. Over time, the SA node may harden and develop scar-like damage (fibrosis) that prevents it from working properly.
### Learn more about the genes associated with Sick sinus syndrome
* HCN4
* MYH6
* SCN5A
## Inheritance Pattern
Most cases of sick sinus syndrome are not inherited. They are described as sporadic, which means they occur in people with no history of the disorder in their family.
When sick sinus syndrome results from mutations in the HCN4 gene, it has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.
When sick sinus syndrome is caused by mutations in the SCN5A gene, it is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Sick sinus syndrome
|
c1837845
| 8,207 |
medlineplus
|
https://medlineplus.gov/genetics/condition/sick-sinus-syndrome/
| 2021-01-27T08:24:35 |
{"gard": ["4880"], "mesh": ["C563907"], "omim": ["608567", "163800", "614090"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) is caused by homozygous mutation in the STRADA gene (608626) on chromosome 17q23.
Clinical Features
Puffenberger et al. (2007) studied 16 distantly related Old Order Mennonite children with a syndrome they designated PMSE for 'polyhydramnios, megalencephaly, and symptomatic epilepsy.' All affected pregnancies were complicated by polyhydramnios. Spontaneous onset of labor occurred between 25 and 36 weeks' gestation in 12 pregnancies. All but 1 affected child had macrocephaly. Seizures started between 3 and 7 months of age in all patients. These were most commonly complex partial seizures that would occasionally spread to involve 1 or both cerebral hemispheres. All patients had severe psychomotor retardation. Four of the 16 patients had atrial septal defects and 1 developed congestive heart failure at 3 months of age. Diabetes insipidus was present in 2 patients who were formally tested, and 2 additional patients had a clinical history suggestive of an osmoregulatory defect. Two patients had bilateral nephrocalcinosis despite essentially normal urinary calcium levels. Six of the 16 children with PMSE syndrome died between ages 7 months and 6 years. Causes of death were status epilepticus in 2, hypovolemic shock secondary to diabetes insipidus, and leukemia.
Bi et al. (2016) reported a 5-year-old boy, born of consanguineous Indian parents, with clinical and genetic features consistent with PMSE. Prenatal ultrasound showed polyhydramnios as early as 12 weeks. He was born at term with feeding difficulties and poor weight gain. At 3 months of age, he developed seizures, which were initially difficult to control. He had global developmental delay, severe psychomotor retardation, severe hypotonia, and marked joint laxity. At age 5, he could cruise with a walker, but remained nonverbal. He had a thin body habitus with decreased muscle mass and minimal subcutaneous fat, tall forehead, narrow face, highly arched eyebrows, wide mouth, tented upper lip, and hypotonic facies with open mouth and drooling. The patient also had nephrocalcinosis with normal renal size and morphology. Head circumference remained at the 75th percentile. Brain imaging showed periventricular white matter signal abnormalities, and EEG showed multifocal epileptiform discharges and generalized background slowing.
Inheritance
The transmission pattern of PMSE in the families reported by Puffenberger et al. (2007) was consistent with autosomal recessive inheritance.
Molecular Genetics
Puffenberger et al. (2007) used single-nucleotide polymorphism (SNP) microarrays to investigate the genetic basis of the disorder in 7 of the 16 children with PMSE available to them for study. Autozygosity mapping was inconclusive, but closer inspection of the data followed by formal SNP copy number analyses showed that all affected patients had homozygous deletions of a single SNP (rs721575), and their parents were hemizygous for this marker. The deleted SNP marked a larger deletion encompassing exons 9 through 13 of the LYK5 gene (608626.0001), which encodes STE20-related adaptor protein (STRAD), a pseudokinase necessary for proper localization and function of serine/threonine kinase 11 (LKB1; 602216).
In an Indian boy with PMSE, Bi et al. (2016) identified a homozygous truncating mutation in the STRADA gene (608626.0002). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.
Pathogenesis
Puffenberger et al. (2007) reported a postmortem neuropathologic study of 1 of the 16 patients, which revealed megalencephaly, ventriculomegaly, cytomegaly, and extensive vacuolization and astrocytosis of white matter. There was abundant antiphosphoribosomal S6 labeling of large cells within the frontal cortex, basal ganglia, hippocampus, and spinal cord, consistent with constitutive activation of the mammalian target of rapomycin (mTOR; 601231) signaling pathway in brain. Puffenberger et al. (2007) postulated that mTOR is constitutively activated as a result of homozygous LYK5 mutations, and that this leads to inappropriate phosphorylation of p70 S6 kinase (see 608938) and phosphorylated S6 protein (180460). Puffenberger et al. (2007) suggested that the cellular mechanisms leading to abnormal brain development from LYK5 deletions may be similar to those of tuberous sclerosis (TSC; see 191100). In both TSC and PMSE syndrome, proliferation of astrocytes may result from constitutive activation of mTOR, either focally, as in TSC, or diffusely, as in PMSE.
Population Genetics
Puffenberger et al. (2007) stated that developmental delay is the presenting problem for 35% of the approximately 125 Amish and Mennonite patients evaluated each year at the Clinic for Special Children in Lancaster County, Pennsylvania. They genotyped 100 healthy Old Order Mennonite controls for the LYK5 deletion and identified four 7-kb deletion carriers, yielding an estimated carrier frequency for the mutant allele in Lancaster County Old Order Mennonites of approximately 4%.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Thin body habitus HEAD & NECK Head \- Macrocephaly Face \- Large forehead \- Long face \- Overgrowth of the mandible \- Hypotonic facies Eyes \- Hypertelorism \- Strabismus \- Peaked eyebrows Nose \- Broad nasal bridge Mouth \- Enlarged mouth \- Open mouth \- Thick lips CARDIOVASCULAR Heart \- Atrial septal defects (in some patients) ABDOMEN Gastrointestinal \- Feeding difficulties GENITOURINARY Kidneys \- Nephrocalcinosis (in some patients) SKELETAL \- Joint laxity (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia \- Skeletal muscle hypoplasia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Seizures, refractory \- Mental retardation \- Poor or absent speech \- Inability to walk \- Difficulty walking \- Multifocal high-voltage spike and slow wave discharges seen on EEG \- Ventriculomegaly \- Cytomegaly seen on brain biopsy \- Vacuolization of the white matter \- Astrocytosis \- Subependymal dysplasia ENDOCRINE FEATURES \- Diabetes insipidus (in some patients) PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Onset of seizures in first months of life \- Developmental stagnation after seizure onset \- Increased frequency among the Amish \- Death in childhood may occur MOLECULAR BASIS \- Caused by mutation in the STE20-related kinase adaptor alpha gene (STRADA, 608626.0001 ) ▲ 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
|
POLYHYDRAMNIOS, MEGALENCEPHALY, AND SYMPTOMATIC EPILEPSY
|
c1970203
| 8,208 |
omim
|
https://www.omim.org/entry/611087
| 2019-09-22T16:03:40 |
{"mesh": ["C567020"], "omim": ["611087"], "orphanet": ["500533"], "synonyms": ["PMSE SYNDROME", "Alternative titles", "PMSE syndrome"]}
|
## Description
Childhood seizures associated with febrile episodes are relatively common and represent the majority of childhood seizures. A febrile convulsion is defined as a seizure event in infancy or childhood, usually occurring between 6 months and 6 years of age, associated with fever but without any evidence of intracranial infection or defined pathologic or traumatic cause (Nabbout et al., 2002). Although the majority of patients do not develop epilepsy, the risk of developing subsequent afebrile seizures is 5 to 7 times higher in those with a history of febrile seizures compared to the general population (Annegers et al., 1987; Hedera et al., 2006).
The FEB1 locus maps to chromosome 8q13-q21.
### Genetic Heterogeneity of Familial Febrile Seizures
FEB3A (604403) is caused by mutation in the SCN1A gene (182389) on chromosome 2q24; FEB3B (see 604403) is caused by mutation in the SCN9A gene (603415) on chromosome 2q24; FEB4 (604352) is caused by mutation in the ADGRV1 gene (602851) on chromosome 5q14; FEB8 (607681) is caused by mutation in the GABRG2 gene (137164) on chromosome 5q31; and FEB11 (614418) is caused by mutation in the CPA6 gene (609562) on chromosome 8q13.
Several loci for familial febrile seizures have been identified: see FEB2 (602477) on chromosome 19p, FEB5 (609255) on chromosome 6q, FEB6 (609253) on chromosome 18p, FEB7 (611515) on chromosome 21q22, FEB9 (611634) on chromosome 3p24.2-p23, and FEB10 (612637) on chromosome 3q26.
A phenotype termed 'generalized epilepsy with febrile seizures plus' (GEFS+; 604233) is a clinical subset of familial febrile convulsions in which affected individuals later develop afebrile seizures. GEFS+ is associated with mutations in several genes.
Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm.
Inheritance
Rich et al. (1987) performed complex segregation analysis on 467 nuclear families ascertained through probands with febrile seizures. Analyses of the entire data indicated that the single-major-locus models could be rejected. However, when families were partitioned on the basis of frequency of febrile seizures in the proband, significant heterogeneity was present. The polygenic model was strongly corroborated in families of probands with a single febrile seizure. In families with probands with multiple febrile seizures, evidence was consistent with a single-major-locus model with nearly dominant seizure susceptibility.
Johnson et al. (1996) carried out a systematic pedigree study of 52 probands; 40 of them (77%) had more than 1 case per family: 1 family had 10 cases, 1 family had 7, 3 families had 6, 2 had 5, 3 had 4, 13 had 3, and 17 had 2 cases. Mode of inheritance in the multicase families best fitted the hypothesis of autosomal dominance with reduced penetrance. Polygenic inheritance could not be excluded for some of the smaller families. There was no support for X-linked or mitochondrial inheritance. Penetrance was calculated to be 0.64. These families had been preselected for increased severity in the probands; thus, 0.64 represents a useful estimate of the upper limit of penetrance and is in agreement with twin studies.
Van Stuijvenberg et al. (1999) studied the characteristics of the first seizure in 51 children with febrile seizures with at least 1 affected first-degree relative compared to 177 affected children with no family history. No evidence for an association between familial febrile seizures and complex characteristics of the initial febrile seizure were demonstrated.
In comparing 83 cases (children with febrile seizures and a first-degree affected relative) and 101 controls (children with febrile seizures but without family history), Pal et al. (2003) found that recurrent febrile seizures were significantly associated with first-degree family history (odds ratio = 2.1). In addition, later occurrence of afebrile seizures was independently associated with recurrent febrile seizures (odds ratio = 3.47).
Population Genetics
Febrile seizures occur in 2 to 5% of all children in the developed world before the age of 5 years (Wallace et al., 1996; Nabbout et al., 2002). In Japanese populations, the incidence is as high as 7% (Bird, 1987). In certain Pacific populations, the incidence is said to be as high as 15%. Approximately 33% of patients who experience a febrile convulsion will have a second one, and 50% of those will have a third. Two to 7% of children who experience febrile convulsions go on to develop afebrile seizure disorders and epilepsy later in life (Johnson et al., 1998).
Mapping
Wallace et al. (1996) identified by linkage analysis an autosomal dominant locus for familial febrile seizures, termed FEB1, on chromosome 8q13-q21. The multipoint lod score of 3.40 was obtained, maximized over different values of penetrance and phenocopy rate, in the region flanked by markers D8S553 and D8S279. The lod score was calculated assuming the disease has a penetrance of 60% and a phenocopy rate of 3%. In the family reported by Wallace et al. (1996), Salzmann et al. (2012) excluded mutations in the CPA6 gene (609562) on chromosome 8q13. However, Salzmann et al. (2012) could not exclude the possibility of a mutation in the promoter or noncoding region, or a copy number variant in that family.
Molecular Genetics
### Associations Pending Confirmation
Dibbens et al. (2010) identified a variant in the HCN2 gene (602781) that resulted in a 9-bp deletion (2156delCGCCGCCGC) removing 3 proline residues at 719 to 721 (delPPP) from a 7-proline repeat close to the cyclic nucleotide-binding domain. The deletion was present in only 3 (0.2%) of 772 controls, but in 3 (2.5%) of 61 patients with febrile seizure and in 3 (2.3%) of 65 patients with generalized epilepsy with febrile seizures plus (GEFS+; 604233). In vitro functional expression studies in Xenopus oocytes showed that the delPPP variant had a 35% increase in current size in response to hyperpolarization compared to wildtype. This current increase would depolarize the membrane potential, taking the neuron closer to the firing potential, and thus could enhance neuronal excitability. The HCN2 delPPP variant was not observed in patients with idiopathic generalized epilepsy (EIG; 600669), who do not have febrile seizures. The findings suggested an association between variation in the HCN2 gene and predisposition to febrile seizures.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, generalized, associated with fever \- Generalized tonic-clonic seizures \- Hypertonic seizures \- Hypotonic seizures \- Seizures occur in absence of intracranial infection or defined pathologic or traumatic cause \- Seizures usually last less than 15 minutes \- Seizures recur in 33% of patients \- Patients show normal psychomotor development \- Between 2 and 7% of children will develop afebrile seizure disorders later in life MISCELLANEOUS \- Onset 3 months of age up to 5 years \- Seizures remit by age 5 years \- Incidence 2-5% of North American children \- Incidence 7-15% in Pacific island populations \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the potassium voltage-gated channel, KQT-like subfamily, member 2 gene (KCNQ2, 602235.0001 ) ▲ 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
|
FEBRILE SEIZURES, FAMILIAL, 1
|
c1852577
| 8,209 |
omim
|
https://www.omim.org/entry/121210
| 2019-09-22T16:42:55 |
{"mesh": ["C565162"], "omim": ["121210"], "synonyms": ["Alternative titles", "CONVULSIONS, FAMILIAL FEBRILE, 1"]}
|
Encephalopathy due to urocanase deficiency is an extremely rare histidine metabolism disorder characterized by urocanic aciduria and other variable manifestations including intellectual deficit and intermittent ataxia in the 4 cases reported to date.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Urocanic aciduria
|
c0268514
| 8,210 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=210128
| 2021-01-23T18:50:51 |
{"gard": ["8539"], "mesh": ["C536479"], "omim": ["276880"], "umls": ["C0268514"], "icd-10": ["E70.8"], "synonyms": ["Encephalopathy due to urocanase deficiency"]}
|
Disease of the lungs
This article is about the disease. For the plant known as "pleurisy root", see Butterfly weed.
Pleurisy
Other namesPleuritis, pleuritic chest pain[1]
Figure A shows normal anatomy. Figure B shows lungs with pleurisy in the right lung, and a pneumothorax of the left lung.
SpecialtyPulmonology
SymptomsSharp chest pain[1]
CausesViral infection, bacterial infection, pneumonia, pulmonary embolism[2]
Diagnostic methodChest X-ray, electrocardiogram (ECG), blood tests[3]
Differential diagnosisPericarditis, heart attack, cholecystitis[3]
TreatmentBased on the underlying cause[3]
MedicationParacetamol (acetaminophen), ibuprofen[4]
Frequency1 million cases per year (United States)[5]
Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity (pleurae).[1] This can result in a sharp chest pain while breathing.[1] Occasionally the pain may be a constant dull ache.[6] Other symptoms may include shortness of breath, cough, fever or weight loss, depending on the underlying cause.[6]
The most common cause is a viral infection.[2] Other causes include bacterial infection, pneumonia, pulmonary embolism, autoimmune disorders, lung cancer, following heart surgery, pancreatitis and asbestosis.[2] Occasionally the cause remains unknown.[2] The underlying mechanism involves the rubbing together of the pleurae instead of smooth gliding.[1] Other conditions that can produce similar symptoms include pericarditis, heart attack, cholecystitis, pulmonary embolism, and pneumothorax.[3] Diagnostic testing may include a chest X-ray, electrocardiogram (ECG), and blood tests.[3][7]
Treatment depends on the underlying cause.[3] Paracetamol (acetaminophen) and ibuprofen may be used to decrease pain.[4] Incentive spirometry may be recommended to encourage larger breaths.[5] About one million people are affected in the United States each year.[5] Descriptions of the condition date from at least as early as 400 BC by Hippocrates.[8]
## Contents
* 1 Signs and symptoms
* 1.1 Related problems
* 1.1.1 Pleural effusion
* 1.1.2 Pneumothorax
* 1.1.3 Hemothorax
* 2 Causes
* 3 Diagnosis
* 3.1 Physical examination
* 3.2 Diagnostic tests
* 3.2.1 Chest x-ray
* 3.2.2 Blood test
* 3.2.3 ECG
* 3.2.4 Ultrasound
* 3.2.5 Computed tomography (CT) scan
* 3.2.6 Magnetic resonance imaging (MRI)
* 3.2.7 Arterial blood gas
* 3.2.8 Thoracentesis
* 3.2.9 Biopsy
* 4 Treatment
* 4.1 Procedures
* 4.2 Medications
* 4.3 Lifestyle changes
* 4.4 Treating the cause
* 4.5 Alternative treatments
* 5 Prognosis
* 6 References
* 7 External links
## Signs and symptoms[edit]
The defining symptom of pleurisy is a sudden sharp, stabbing, burning or dull pain in the right or left side of the chest during breathing, especially when one inhales and exhales.[9] It feels worse with deep breathing, coughing, sneezing, or laughing. The pain may stay in one place, or it may spread to the shoulder or back.[10] Sometimes, it becomes a fairly constant dull ache.[11]
Depending on its cause, pleuritic chest pain may be accompanied by other symptoms:[12]
* Dry cough
* Fever and chills
* Rapid, shallow breathing
* Shortness of breath
* Fast heart rate
* Sore throat followed by pain and swelling in the joints
### Related problems[edit]
Pleurisy is often associated with complications that affect the pleural space.
#### Pleural effusion[edit]
In some cases of pleurisy, excess fluid builds up in the pleural space. This is called a pleural effusion. The buildup of excess fluid, will more often than not force the two layers of the pleura apart so they don't rub against each other when breathing. This can relieve the pain of pleurisy. A large amount of fluid can result in collapse of the lung. This can make it difficult to breathe.
In some cases of pleural effusion, the excess fluid becomes infected and turns into an abscess. This is called an empyema.
Pleural effusion involving fibrinous exudates in the fluid may be called fibrinous pleurisy, which sometimes occurs as a later stage of pleurisy.
A person can develop a pleural effusion in the absence of pleurisy. For example, pneumonia, heart failure, cancer, or a pulmonary embolism can lead to a pleural effusion.
#### Pneumothorax[edit]
Air or gas also can build up in the pleural space. This is called a pneumothorax. It can result from acute lung injury or a lung disease like emphysema. Lung procedures, like surgery, drainage of fluid with a needle, examination of the lung from the inside with a light and a camera, or mechanical ventilation, also can cause a pneumothorax.
The most common symptom is sudden pain in one side of the lung and shortness of breath. A pneumothorax also can put pressure on the lung and cause it to collapse.
If the pneumothorax is small, it may go away on its own. If large, a chest tube is placed through the skin and chest wall into the pleural space to remove the air.
#### Hemothorax[edit]
Blood also can collect in the pleural space. This is called hemothorax. The most common cause is injury to the chest from blunt force or surgery on the heart or chest. Hemothorax also can occur in people with lung or pleural cancer.
Hemothorax can put pressure on the lung and force it to collapse. It also can cause shock, a state of hypoperfusion in which an insufficient amount of blood is able to reach the organs.
## Causes[edit]
Pleurisy
Pleural linings and space (marked in blue)
The pleural space can be invaded by fluid, air, and particles from other parts of the body, which fairly complicates diagnosis.[12][13] Viral infection (coxsackie B virus, HRSV, CMV, adenovirus, EBV, parainfluenza, influenza, COVID-19) is the most common cause of pleurisy. However, many other different conditions can cause pleuritic chest pain:[11]
* Aortic dissections
* Autoimmune disorders such as systemic lupus erythematosus (or drug-induced lupus erythematosus), Autoimmune hepatitis (AIH), rheumatoid arthritis and Behçet's disease.
* Bacterial infections associated with pneumonia and tuberculosis
* Chest injuries (blunt or penetrating)
* Familial Mediterranean fever, an inherited condition that often causes fever and swelling in the abdomen or the lungs
* Fungal or parasitic infections
* Heart surgery, especially coronary-artery bypass grafting
* Cardiac problems (ischemia, pericarditis)
* Inflammatory bowel disease
* Lung cancer and lymphoma
* Other lung diseases like cystic fibrosis, sarcoidosis, asbestosis, lymphangioleiomyomatosis, and mesothelioma
* Pneumothorax
* Pulmonary embolisms, which are blood clots that enter the lungs
When the space between the pleurae starts to fill with fluid, as in pleural effusion, the chest pain can be eased but a shortness of breath can result, since the lungs need room to expand during breathing. Some cases of pleuritic chest pain are idiopathic, which means that the exact cause cannot be determined.
## Diagnosis[edit]
A diagnosis of pleurisy or another pleural condition is based on a medical history, physical examinations, and diagnostic tests.[12] The goals are to rule out other sources of the symptoms and to find the cause of the pleurisy so that the underlying disorder can be treated.
### Physical examination[edit]
A doctor uses a stethoscope to listen to the breathing. This method detects any unusual sounds in the lungs. A person with pleurisy may have inflamed layers of the pleurae that make a rough, scratchy sound as they rub against each other during breathing. This is called pleural friction rub.
### Diagnostic tests[edit]
Depending on the results of the physical examination, diagnostic tests are sometimes performed.
#### Chest x-ray[edit]
A chest X-ray takes a picture of the heart and lungs. It may show air or fluid in the pleural space. It also may show the cause (e.g., pneumonia, a fractured rib, or a lung tumor) of the pleurisy.
Sometimes an x-ray is taken while lying on the painful side. This may show fluid, as well as changes in fluid position, that did not appear in the vertical x-ray.
#### Blood test[edit]
Blood tests can detect bacterial or viral infections, pneumonia, rheumatic fever, a pulmonary embolism, or lupus.
#### ECG[edit]
Electrocardiography test can determine if a heart condition contributes to the symptoms.
#### Ultrasound[edit]
Ultrasonography uses sound waves to create an image. It may show where fluid is located in the chest. It also can show some tumors. Although ultrasound may detect fluid around the lungs, also known as a pleural effusion, sound waves are scattered by air. Therefore, an actual picture of the lungs cannot be obtained with ultrasonography.
#### Computed tomography (CT) scan[edit]
A CT scan provides a computer-generated picture of the lungs that can show pockets of fluid. It also may show signs of pneumonia, a lung abscess, or a tumor.
#### Magnetic resonance imaging (MRI)[edit]
Magnetic resonance imaging (MRI), also called nuclear magnetic resonance (NMR) scanning, uses powerful magnets to show pleural effusions and tumors.
#### Arterial blood gas[edit]
In arterial blood-gas sampling, a small amount of blood is taken from an artery, usually in the wrist. The blood is then checked for oxygen and carbon-dioxide levels. This test shows how well the lungs are taking in oxygen.
#### Thoracentesis[edit]
The illustration shows a person undergoing thoracentesis. The person sits upright and leans on a table. Excess fluid from the pleural space is drained into a bag.
Once the presence of an excess fluid in the pleural cavity, or pleural effusion, is suspected and location of fluid is confirmed, a sample of fluid can be removed for testing.[14] The procedure to remove fluid in the chest is called a diagnostic thoracentesis.[15] The doctor inserts a small needle or a thin, hollow, plastic tube in the chest wall and withdraws fluid.[16]
Thoracentesis can be done in the doctor's office or at the hospital. Ultrasound is used to guide the needle to the fluid that is trapped in small pockets around the lungs.
Thoracentesis usually does not cause serious complications. Generally, a chest x-ray is done after the procedure to evaluate the lungs. Possible complications of thoracentesis include the following:
* Bleeding and bruising where the needle went in. In rare cases, bleeding may occur in or around the lung. The doctor can use a chest tube to drain the blood. In some cases, surgery is needed.
* Infection where the needle went in
* Injury to the liver or spleen (in rare cases)
* Pain.
* Pneumothorax, or buildup of air in the pleural space, with a collapsed or partially collapsed lung. Sometimes air comes in through the needle or the needle makes a hole in the lung. Usually, a hole seals itself—but sometimes air builds up around the lung and makes it collapse. A chest tube removes the air and lets the lung expand again.
The lung fluid is examined under a microscope and is evaluated for the presence of chemicals and for its color and texture. The degree of clarity is an indicator of infection, cancer, or other conditions that may be causing the buildup of fluid or blood in the pleural space.
#### Biopsy[edit]
If tuberculosis or cancer is suspected, a small piece of the pleura may be examined under a microscope to make a definitive diagnosis. This is called a biopsy.
Several approaches to taking tissue samples are available
1. Insertion of a needle through the skin on the chest to remove a small sample of the outer layer of the pleura
2. Insertion of a small tube with a light on the end (endoscope) into tiny cuts in the chest wall to visualize the pleura, and biopsy of small pieces of tissue through the endoscope
3. Removal of a sample of the pleura through a small cut in the chest wall (open pleural biopsy), usually done if the sample from the needle biopsy is too small for accurate diagnosis
## Treatment[edit]
Treatment has several goals:[12]
* Relief of symptoms
* Removal of the fluid, air, or blood from the pleural space
* Treatment of the underlying condition
### Procedures[edit]
If large amounts of fluid, air, or blood are not removed from the pleural space, they may cause the lung to collapse.
The surgical procedures used to drain fluid, air, or blood from the pleural space are as follows:
* During thoracentesis, a needle or a thin, hollow, plastic tube is inserted through the ribs in the back of the chest into the chest wall. A syringe is attached to draw fluid out of the chest. This procedure can remove more than 6 cups (1.5 litres) of fluid at a time.
* When larger amounts of fluid must be removed, a chest tube may be inserted through the chest wall. The doctor injects a local painkiller into the area of the chest wall outside where the fluid is. A plastic tube is then inserted into the chest between two ribs. The tube is connected to a box that suctions the fluid out. A chest x-ray is taken to check the tube's position.
* A chest tube is also used to drain blood and air from the pleural space. This can take several days. The tube is left in place, and the patient usually stays in the hospital during this time.
* Sometimes the fluid contains thick pus or blood clots, or it may have formed a hard skin or peel. This makes it harder to drain the fluid. To help break up the pus or blood clots, the doctor may use the chest tube to put certain medicines into the pleural space. These medicines are called fibrinolytics. If the pus or blood clots still do not drain out, surgery may be necessary.
### Medications[edit]
A couple of medications are used to relieve pleurisy symptoms:
* Paracetamol (acetaminophen) or anti-inflammatory agents to control pain and decrease inflammation. Only indomethacin (brand name Indocin) has been studied with respect to relief of pleurisy.[17]
* Codeine-based cough syrups to control the cough
There may be a role for the use of corticosteroids (for tuberculous pleurisy), tacrolimus (Prograf) and methotrexate (Trexall, Rheumatrex) in the treatment of pleurisy. Further studies are needed.
### Lifestyle changes[edit]
The following may be helpful in the management of pleurisy:
* Lying on the painful side may be more comfortable
* Breathing deeply and coughing to clear mucus as the pain eases. Otherwise, pneumonia may develop.
* Getting rest
### Treating the cause[edit]
Ideally, the treatment of pleurisy is aimed at eliminating the underlying cause of the disease.
* If the pleural fluid is infected, treatment involves antibiotics and draining the fluid. If the infection is tuberculosis or from a fungus, treatment involves long-term use of antibiotics or antifungal medicines.
* If the fluid is caused by tumors of the pleura, it may build up again quickly after it is drained. Sometimes anti-tumor medicines prevent further fluid buildup. If they don't, the doctor may seal the pleural space. This is called pleurodesis. Pleurodesis involves the drainage of all the fluid out of the chest through a chest tube. A substance is inserted through the chest tube into the pleural space. This substance irritates the surface of the pleura. This causes the two layers of the pleurae to squeeze shut so there is no room for more fluid to build up.
* Chemotherapy or radiation treatment also may be used to reduce the size of the tumors.
* If congestive heart failure is causing the fluid buildup, treatment usually includes diuretics and other medicines.
The treatment for pleurisy depends on its origin and is prescribed by a physician on a base of an individual assessment.[18] Paracetamol (acetaminophen) and amoxicillin, or other antibiotics in case of bacterial infections, are common remedies dispensed by doctors to relieve the initial symptoms and pain in the chest, while viral infections are self-limited. Non-steroidal anti-inflammatory drugs (NSAIDs), preferably indometacin, are usually employed as pain control agents.[12]
### Alternative treatments[edit]
A number of alternative or complementary medicines are being investigated for their anti-inflammatory properties, and their use in pleurisy. At this time, clinical trials of these compounds have not been performed.
Extracts from the Brazilian folk remedy Wilbrandia ebracteata ("Taiuia") have been shown to reduce inflammation in the pleural cavity of mice.[19][20] The extract is thought to inhibit the same enzyme, cyclooxygenase-2 (COX-2), as the non-steroidal anti-inflammatory drugs.[20]
## Prognosis[edit]
Pleurisy and other disorders of the pleurae can be serious, depending on what caused them. Generally, pleurisy treatment has an excellent prognosis, but if left untreated it can cause severe complications. For example, a resulting pulmonary heart disease cor pulmonale, which manifests itself with an inflammation of the arms and legs, can lead to heart failure. If the conditions that caused the pleurisy or other pleural disorders were adequately diagnosed and treated early, one can expect a full recovery. Help of a pulmonologist (respiratory physician in the U.K. and Australia) may be enlisted to address the underlying cause and chart post-illness rehabilitation.
## References[edit]
1. ^ a b c d e "What Are Pleurisy and Other Pleural Disorders?". NHLBI. 21 September 2011. Archived from the original on 8 November 2016. Retrieved 1 November 2016.
2. ^ a b c d "What Causes Pleurisy and Other Pleural Disorders?". NHLBI. 21 September 2011. Archived from the original on 8 October 2016. Retrieved 1 November 2016.
3. ^ a b c d e f Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017: 5 Books in 1. Elsevier Health Sciences. p. 981. ISBN 9780323448383. Archived from the original on 3 November 2016.
4. ^ a b "How Are Pleurisy and Other Pleural Disorders Treated?". NHLBI. 21 September 2011. Archived from the original on 3 November 2016. Retrieved 1 November 2016.
5. ^ a b c Disease & Drug Consult: Respiratory Disorders. Lippincott Williams & Wilkins. 2012. p. Pleurisy. ISBN 9781451151947. Archived from the original on 3 November 2016.
6. ^ a b "What Are the Signs and Symptoms of Pleurisy and Other Pleural Disorders". NHLBI. 21 September 2011. Archived from the original on 8 October 2016. Retrieved 1 November 2016.
7. ^ Kass, SM; Williams, PM; Reamy, BV (1 May 2007). "Pleurisy". American Family Physician. 75 (9): 1357–64. PMID 17508531.
8. ^ Light, Richard W.; Lee, Y. C. Gary (2008). Textbook of Pleural Diseases Second Edition (2 ed.). CRC Press. p. 2. ISBN 9780340940174. Archived from the original on 3 November 2016.
9. ^ "The Lung Center: Understanding Pleurisy" (PDF). An online information portal for the community. The Lung Center, New Deli, India. Archived from the original (PDF) on 1 September 2012. Retrieved 22 June 2013.
10. ^ Beth Walsh, MA. Pleurisy (pleuritis). Archived 9 February 2013 at the Wayback Machine
11. ^ a b Ferri, Fred F. Ferri's Clinical Advisor 2012. Philadelphia, PA: Elsevier Mosby, 2012, p. 790.
12. ^ a b c d e Sara M. Kass, CDR, MC, USN, Pamela M. Williams, MAJ, USAF, MC, and Brian V. Reamy, COL, USAF, MC, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Pleurisy. American Family Physician. 2007, 1 May; 75(9):1357–1364. Archived 14 February 2015 at the Wayback MachinePDF Archived 31 January 2016 at the Wayback Machine
13. ^ Maskell, Nick, and Ann Millar. Oxford Desk Reference. Oxford: Oxford University Press, 2009. Chapter 14. Pleural Disease. PDF Archived 8 October 2013 at the Wayback Machine
14. ^ Raed A. Dweik. Cleveland Clinic Center for Continuous Education: Pleural Disease. Archived 8 May 2013 at the Wayback Machine
15. ^ Light, R.W. Diagnostic principles in pleural disease. European Respiratory Journal, 1997 Feb; 10(2): 476–81.[1]
16. ^ Sahn, Steven A. Pleural Disease. Philadelphia: Saunders, 2006.
17. ^ Klein RC (October 1984). "Effects of indomethacin on pleural pain". South. Med. J. 77 (10): 1253–4. doi:10.1097/00007611-198410000-00011. PMID 6207594. S2CID 28649967.
18. ^ Fishman, Alfred P., and Jack A. Elias. Fishman's Pulmonary Diseases and Disorders. New York: McGraw-Hill, Health Professions Division, 1997.
19. ^ Peters RR, Saleh TF, Lora M, et al. (1999). "Anti-inflammatory effects of the products from Wilbrandia ebracteata on carrageenan-induced pleurisy in mice". Life Sci. 64 (26): 2429–37. doi:10.1016/S0024-3205(99)00200-3. PMID 10403502.
20. ^ a b Siqueira JM, Peters RR, Gazola AC, et al. (March 2007). "Anti-inflammatory effects of a triterpenoid isolated from Wilbrandia ebracteata Cogn". Life Sci. 80 (15): 1382–7. doi:10.1016/j.lfs.2006.12.021. PMID 17286991.
## External links[edit]
Classification
D
* ICD-10: J90, R09.1
* ICD-9-CM: 511
* MeSH: D010998
* DiseasesDB: 29361
External resources
* MedlinePlus: 001371
* Tim Kenny; Colin Tidy (2002–2013). "Pleurisy and Pleuritic Pain". patient.info. Retrieved 30 June 2013.
* The Lung Association of Canada explanation of Pleurisy (also available in French)
* Pleurisy by the American Academy of Family Physicians
* v
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Authority control
* NDL: 00569657
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
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*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
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*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
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*[IM]: intramuscular injection
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*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pleurisy
|
c0032231
| 8,211 |
wikipedia
|
https://en.wikipedia.org/wiki/Pleurisy
| 2021-01-18T18:42:50 |
{"mesh": ["D010998"], "umls": ["C0032231"], "icd-10": ["J90", "R09.1"], "wikidata": ["Q55998"]}
|
A rare, genetic lysosomal storage disease characterized by accumulation of glycosaminoglycans in connective tissue which results in progressive multisystem involvement with severity ranging from mild to severe. The most consistent features include musculoskeletal involvement (particularly dysostosis multiplex, joint restriction, thorax abnormalities, and short stature), limited vocabulary, intellectual disability, coarse facies with a short neck, pulmonary involvement (predominantly decreased pulmonary function), corneal clouding, and cardiac valve disease.
## Epidemiology
The prevalence at birth is reported to range between 1/345,000 -5,000,000. However, the frequency of the disease may be underestimated as the most frequent presentation is the antenatal form, which remains underdiagnosed.
## Clinical description
Signs are extremely variable: there are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, small stature and severe hypotonia and neurological involvement that ultimately lead to profound intellectual deficit in patients who survive. At the other end of the spectrum, there are very mild cases that are discovered during adolescence or adulthood following presentation with thoracic kyphosis.
## Etiology
Mutations in the gene GUSB (7q11.21) causes beta-D-glucuronidase deficiency, which leads to accumulation of several glycosaminoglycans (dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS)) in lysosomes.
## Diagnostic methods
Diagnosis is supported by x-ray evidence of dysostosis multiplex and detection of increased levels of urinary glycosaminoglycan (either CS alone or CS+HS+DS) excretion, although this sign may be absent in adult forms. Diagnosis is confirmed by demonstration of beta-D-glucuronidase deficiency in cultured leucocytes or fibroblasts. Pseudodeficient alleles make mild forms more difficult to identify and prenatal diagnosis difficult.
## Differential diagnosis
Differential diagnosis includes other types of mucopolysaccharidosis (MPS) and oligosaccharidosis. The determination of enzymatic activity in leucocytes allows heterozygous individuals to be detected for the severe forms. When the two mutations have been identified in the index patient, the detection of heterozygous relatives can be performed accurately.
## Antenatal diagnosis
Diagnosis is possible in forms with in utero presentation and may prevent recurrence of pregnancies leading to in utero death or late termination of the pregnancy. Prenatal diagnosis (by molecular analysis or measurement of enzyme activity in trophoblasts or amniocytes) can be offered to parents with an affected child. Parents should be made aware of the availability of enzyme replacement therapy (ERT).
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
ERT with recombinant human beta-glucuronidase has been approved in Europe and the USA for MPS type 7, and has shown improvement in walking, lung function and hepatosplenomegaly in clinical trials. Still, multidisciplinary management allows adapted symptomatic treatment, which is essential for improving the quality of life of the patients. In late-onset forms, treatment is mainly orthopedic. Bone marrow transplantation has been successful in three of five patients.
## Prognosis
Prognosis is typically poor for antenatal forms, often leading to death in utero. Neonatal and childhood forms typically have a very limited life expectancy, whereas milder forms have a prolonged survival. Whilst ERT is now available, long term outcome data are not yet available on the ERT treated 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
|
Mucopolysaccharidosis type 7
|
c0085132
| 8,212 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=584
| 2021-01-23T18:57:19 |
{"gard": ["7096"], "mesh": ["D016538"], "omim": ["253220"], "umls": ["C0085132"], "icd-10": ["E76.2"], "synonyms": ["Beta-glucuronidase deficiency", "MPS7", "MPSVII", "Mucopolysaccharidosis type VII", "Sly disease"]}
|
Progressive muscular atrophy
Other namesDuchenne–Aran muscular atrophy, others
SpecialtyNeurology
Progressive muscular atrophy (PMA) is a very rare subtype of motor neuron disease (MND) that affects only the lower motor neurons. PMA is thought to account for around 4% of all MND cases.[1] This is in contrast to amyotrophic lateral sclerosis (ALS), the most common form of MND, which affects both the upper and lower motor neurons, or primary lateral sclerosis, another rare MND variant, which affects only the upper motor neurons. The distinction is important because PMA is associated with a better prognosis than classic ALS.
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 2.1 Differential diagnosis
* 3 Prognosis
* 4 History
* 4.1 Disease or syndrome
* 5 Notable cases
* 6 References
* 7 External links
## Signs and symptoms[edit]
As a result of lower motor neuron degeneration, the symptoms of PMA include:
* atrophy
* fasciculations
* muscle weakness
Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as flail limb either flail arm or flail leg, and are associated with a better prognosis.[1]
## Diagnosis[edit]
PMA is a diagnosis of exclusion, there is no specific test which can conclusively establish whether a patient has the condition. Instead, a number of other possibilities have to be ruled out, such as multifocal motor neuropathy or spinal muscular atrophy. Tests used in the diagnostic process include MRI, clinical examination, and EMG. EMG tests in patients who do have PMA usually show denervation (neuron death) in most affected body parts, and in some unaffected parts too.[2]
It typically takes longer to be diagnosed with PMA than ALS, an average of 20 months for PMA vs 15 months in ALS/MND.
### Differential diagnosis[edit]
In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the absence of:
* brisk reflexes
* spasticity
* Babinski's sign
* emotional lability
## Prognosis[edit]
The importance of correctly recognizing progressive muscular atrophy as opposed to ALS is important for several reasons.
* 1) the prognosis is a little better. A recent study found the 5-year survival rate in PMA to be 33% (vs 20% in ALS) and the 10-year survival rate to be 12% (vs 6% in ALS).[1]
* 2) Patients with PMA do not suffer from the cognitive change identified in certain groups of patients with MND.[3]
* 3) Because PMA patients do not have UMN signs, they usually do not meet the "World Federation of Neurology El Escorial Research Criteria" for “Definite” or “Probable” ALS and so are ineligible to participate in the majority of clinical research trials such as drugs trials or brain scans.[1]
* 4) Because of its rarity (even compared to ALS) and confusion about the condition, some insurance policies or local healthcare policies may not recognize PMA as being the life-changing illness that it is. In cases where being classified as being PMA rather than ALS is likely to restrict access to services, it may be preferable to be diagnosed as "slowly progressive ALS" or "lower motor neuron predominant" ALS.
An initial diagnosis of PMA could turn out to be slowly progressive ALS many years later, sometimes even decades after the initial diagnosis. The occurrence of upper motor neuron symptoms such as brisk reflexes, spasticity, or a Babinski sign would indicate a progression to ALS; the correct diagnosis is also occasionally made on autopsy.[4][5]
## History[edit]
Despite being rarer than ALS, PMA was described earlier, when in 1850 French neurologist François Aran described 11 cases which he termed atrophie musculaire progressive. Contemporary neurologist Guillaume-Benjamin-Amand Duchenne de Boulogne English: /duːˈʃɛn/ also claimed to have described the condition 1 year earlier, although the written report was never found.[6] The condition has been called progressive muscular atrophy (PMA),[7] spinal muscular atrophy (SMA),[7] Aran–Duchenne disease,[6][7] Duchenne–Aran disease,[6] Aran–Duchenne muscular atrophy,[7] and Duchenne–Aran muscular atrophy. The name "spinal muscular atrophy" is ambiguous as it refers to any of various spinal muscular atrophies, including the autosomal recessive spinal muscular atrophy caused by a genetic defect in the SMN1 gene.
### Disease or syndrome[edit]
Since its initial description in 1850, there has been debate in the scientific literature over whether PMA is a distinct disease with its own characteristics, or if lies somewhere on a spectrum with ALS, PLS, and PBP. Jean-Martin Charcot, who first described ALS in 1870, felt that PMA was a separate condition, with degeneration of the lower motor neurons the most important lesion, whereas in ALS it was the upper motor neuron degeneration that was primary, with lower motor neuron degeneration being secondary. Such views still exist in archaic terms for PMA such as "Primary progressive spinal muscular atrophy". Throughout the course of the late 19th century, other conditions were discovered which had previously been thought to be PMA, such as pseudo-hypertrophic paralysis, hereditary muscular atrophy, progressive myopathy, progressive muscular dystrophy, peripheral neuritis, and syringomyelia.[6]
The neurologists Joseph Jules Dejerine and William Richard Gowers were among those who felt that PMA was part of a spectrum of motor neuron disease which included ALS, PMA, and PBP, in part because it was almost impossible to distinguish the conditions at autopsy. Other researchers have suggested that PMA is just ALS in an earlier stage of progression, because although the upper motor neurons appear unaffected on clinical examination there are in fact detectable pathological signs of upper motor neuron damage on autopsy.[6]
Also, no gene has been linked specifically to PMA, and the disorder does not appear in the OMIM database.
In favour of considering PMA a separate disease, some patients with PMA live for decades after diagnosis, which would be unusual in typical ALS.[6]
To this day, terminology around these diseases remains confusing because in the United Kingdom motor neurone disease refers to both ALS specifically and to the spectrum of ALS, PMA, PLS, and PBP. In the United States the most common terms are ALS (both specifically for ALS and as a blanket term) or Lou Gehrig's disease.
## Notable cases[edit]
* Mike Gregory \- Former Great Britain rugby league captain and head coach at Wigan RLFC
* Rob Rensenbrink \- Former Netherlands and Anderlecht football player
## References[edit]
1. ^ a b c d Wijesekera LC, Mathers S, Talman P, Galtrey C, Parkinson MH, Ganesalingam J, Willey E, Ampong MA, Ellis CM, Shaw CE, Al-Chalabi A, Leigh PN (Mar 2009). "Natural history and clinical features of the flail arm and flail leg ALS variants". Neurology. 72 (12): 1087–1094. doi:10.1212/01.wnl.0000345041.83406.a2. PMC 2821838. PMID 19307543.
2. ^ Visser J, de Visser M, Van den Berg-Vos RM, Van den Berg LH, Wokke JH, de Jong JM, Franssen H (May 2008). "Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy". J. Neurol. 255 (6): 903–909. doi:10.1007/s00415-008-0813-y. PMID 18484238.
3. ^ Wicks P, Abrahams S, Leigh PN, Williams T, Goldstein LH (Nov 2006). "Absence of cognitive, behavioral, or emotional dysfunction in progressive muscular atrophy". Neurology. 67 (9): 1718–1719. doi:10.1212/01.wnl.0000242726.36625.f3. PMID 17101922.
4. ^ Tsuchiya K, Sano M, Shiotsu H, Akiyama H, Watabiki S, Taki K, Kondo H, Nakano I, Ikeda K (Sep 2004). "Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists: additional autopsy case with a clinical course of 19 years". Neuropathology. 24 (3): 228–235. doi:10.1111/j.1440-1789.2004.00546.x. PMID 15484701.
5. ^ Ince PG, Evans J, Knopp M, Forster G, Hamdalla HH, Wharton SB, Shaw PJ (Apr 2003). "Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS". Neurology. 60 (8): 1252–1258. doi:10.1212/01.wnl.0000058901.75728.4e. PMID 12707426.
6. ^ a b c d e f Visser J, de Jong JM, de Visser M (Feb 2008). "The history of progressive muscular atrophy: Syndrome or disease?". Neurology. 70 (9): 723–727. doi:10.1212/01.wnl.0000302187.20239.93. PMID 18299524.
7. ^ a b c d Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
## External links[edit]
Classification
D
* ICD-9-CM: 335.21
* MeSH: D009134
* DiseasesDB: 29149
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Progressive muscular atrophy
|
c0917981
| 8,213 |
wikipedia
|
https://en.wikipedia.org/wiki/Progressive_muscular_atrophy
| 2021-01-18T18:58:12 |
{"mesh": ["D009134"], "orphanet": ["454706"], "wikidata": ["Q2279175"]}
|
Confluent and reticulated papillomatosis of Gougerot and Carteaud
Other namesConfluent and reticulated papillomatosis, Familial cutaneous papillomatosis, Familial occurrence of confluent and reticulated papillomatosis[1][2]
SpecialtyDermatology
Confluent and reticulated papillomatosis of Gougerot and Carteaud is an uncommon but distinctive acquired ichthyosiform dermatosis characterized by persistent dark, scaly, papules and plaques that tend to be localized predominantly on the central trunk.[3]
## Contents
* 1 Eponym
* 2 See also
* 3 References
* 4 External links
## Eponym[edit]
Henri Gougerot and Alexandre Carteaud originally described the condition in 1927.[4] The cause remains unknown, but the observation that the condition may clear with Minocycline[5] turned attention to an infectious agent. Actinomycete Dietzia strain X was isolated from one individual.[6] Other antibiotics found useful include azithromycin, fusidic acid, clarithromycin, erythromycin, tetracycline and cefdinir.[7]
## See also[edit]
* Ichthyosis
* Acquired ichthyosis
* List of cutaneous conditions
## References[edit]
1. ^ Odom, Richard B.; Davidsohn, Israel; James, William D.; Henry, John Bernard; Berger, Timothy G.; Clinical diagnosis by laboratory methods; Dirk M. Elston (2006). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders Elsevier. p. 207. ISBN 0-7216-2921-0.
2. ^ Online Mendelian Inheritance in Man (OMIM): 167900
3. ^ Freedberg, Irwin M.; Fitzpatrick, Thomas B. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). New York: McGraw-Hill, Medical Pub. Division. pp. 494–5. ISBN 0-07-138076-0.
4. ^ Gougerot H, Carteaud A (1927). "Papillomatose pigmentee innominee". Bull Soc Fr Dermatol Syphilol. 34: 719.
5. ^ Wiley Interscience
6. ^ Natarajan S, Milne D, Jones AL, Goodfellow M, Perry J, Koerner RJ (October 2005). "Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis". Br. J. Dermatol. 153 (4): 825–7. doi:10.1111/j.1365-2133.2005.06785.x. PMID 16181469. S2CID 40122316.
7. ^ Scheinfeld N (2006). "Confluent and reticulated papillomatosis : a review of the literature". Am J Clin Dermatol. 7 (5): 305–13. doi:10.2165/00128071-200607050-00004. PMID 17007541. S2CID 25749839.
## External links[edit]
Classification
D
* ICD-10: L83
* OMIM: 167900
* MeSH: C566832
* v
* t
* e
Cutaneous keratosis, ulcer, atrophy, and necrobiosis
Epidermal thickening
* keratoderma: Keratoderma climactericum
* Paraneoplastic keratoderma
* Acrokeratosis paraneoplastica of Bazex
* Aquagenic keratoderma
* Drug-induced keratoderma
* psoriasis
* Keratoderma blennorrhagicum
* keratosis: Seborrheic keratosis
* Clonal seborrheic keratosis
* Common seborrheic keratosis
* Irritated seborrheic keratosis
* Seborrheic keratosis with squamous atypia
* Reticulated seborrheic keratosis
* Dermatosis papulosa nigra
* Keratosis punctata of the palmar creases
* other hyperkeratosis: Acanthosis nigricans
* Confluent and reticulated papillomatosis
* Callus
* Ichthyosis acquisita
* Arsenical keratosis
* Chronic scar keratosis
* Hyperkeratosis lenticularis perstans
* Hydrocarbon keratosis
* Hyperkeratosis of the nipple and areola
* Inverted follicular keratosis
* Lichenoid keratosis
* Multiple minute digitate hyperkeratosis
* PUVA keratosis
* Reactional keratosis
* Stucco keratosis
* Thermal keratosis
* Viral keratosis
* Warty dyskeratoma
* Waxy keratosis of childhood
* other hypertrophy: Keloid
* Hypertrophic scar
* Cutis verticis gyrata
Necrobiosis/granuloma
Necrobiotic/palisading
* Granuloma annulare
* Perforating
* Generalized
* Subcutaneous
* Granuloma annulare in HIV disease
* Localized granuloma annulare
* Patch-type granuloma annulare
* Necrobiosis lipoidica
* Annular elastolytic giant-cell granuloma
* Granuloma multiforme
* Necrobiotic xanthogranuloma
* Palisaded neutrophilic and granulomatous dermatitis
* Rheumatoid nodulosis
* Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction
Foreign body granuloma
* Beryllium granuloma
* Mercury granuloma
* Silica granuloma
* Silicone granuloma
* Zirconium granuloma
* Soot tattoo
* Tattoo
* Carbon stain
Other/ungrouped
* eosinophilic dermatosis
* Granuloma faciale
Dermis/
localized CTD
Cutaneous lupus
erythematosus
* chronic: Discoid
* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
This Genodermatoses 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
|
Confluent and reticulated papillomatosis
|
c0263385
| 8,214 |
wikipedia
|
https://en.wikipedia.org/wiki/Confluent_and_reticulated_papillomatosis
| 2021-01-18T18:37:57 |
{"mesh": ["C566832"], "umls": ["C1868648", "C0263385"], "icd-10": ["L83"], "wikidata": ["Q5160236"]}
|
A rare, genetic, neurometabolic disease characterized by early onset encephalopathy with progressive microcephaly, severe global development delay, seizures, hypotonia, feeding difficulties, variable cardiac abnormalities, and cataracts. Brain MRI shows distinct pattern with high T2 signal and restricted diffusion in the posterior limb of the internal capsule in combination with delayed myelination and progressive cerebral atrophy. The disease is typically fatal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement
|
c4225256
| 8,215 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=457375
| 2021-01-23T18:01:57 |
{"omim": ["616647"], "icd-10": ["G40.4"], "synonyms": ["Martsolf-like syndrome"]}
|
A rare congenital limb malformation characterized by partial or total absence of the radius.
## Epidemiology
The disorder occurs in 1/5,000-30,000 live births, and is slightly more common in males than in females (sex ratio of 3:2).
## Clinical description
The disorder is bilateral in 60% of cases and the right side is more commonly involved than the left. The degree of malformation varies greatly. In mild cases, only a minor shortening of the radius is present. In the most severe cases in contrast, the radius is completely absent (including presence of aberrant muscles, nerves, tendons, ligaments and blood vessels). The disorder is thus characterized by varying degree of deficiencies of the radius, carpal bones, and the thumb that produces radial deviation of the hand and marked shortening of the forearm. There may also be underdevelopment or absence of the thumb, and malformation of the elbow joint with restricted motion. Radial longitudinal deficiency is frequently (67%) associated with other congenital anomalies or syndromes, including chromosomal anomalies (trisomy 13, 18 and 21), Holt-Oram syndrome, Roberts syndrome, Rothmund-Thomson syndrome, thrombocytopenia-absent radius (TAR) syndrome, Townes-Brocks syndrome, VACTERL association and Fanconi anemia.
## Etiology
The etiology remains unknown. The deformities are believed to develop early in pregnancy, between the 26th and 52th day of gestation. The disorder is being caused by reduction in FGF function.
## Diagnostic methods
Diagnosis is based on clinical examination and X-rays. In utero, prenatal ultrasound may potentially detect this malformation and thus be a valuable imaging modality for early diagnosis.
## Antenatal diagnosis
Prenatal diagnosis is possible using ultrasound, 3D-ultrasound or fetal magnetic resonance imaging.
## Genetic counseling
Approximately 5-10% of cases are familial. Routine genetic counseling is recommended for these cases.
## Management and treatment
Management aims at reducing the functional deficit. Initial therapy consists of straightening of the hand and stabilization of the wrist by serial splinting or casting that should be undertaken shortly after birth. Various surgical methods of correction have been described, such as soft tissue releases with or without ulnar osteotomy, soft tissue distraction to distalize the hand, centralization and radialization, pollicization, microvascular epiphyseal transfer and forearm lengthening.
## Prognosis
The prognosis is generally good. If an early individualized treatment plan is followed a good clinical outcome can be achieved. However, the more extensive the radial longitudinal deficiency type, the more impaired is the finger function and mobility.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Radial hemimelia
|
c0265582
| 8,216 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93321
| 2021-01-23T18:00:07 |
{"gard": ["225"], "icd-10": ["Q71.4"], "synonyms": ["Congenital longitudinal deficiency of the radius", "Radial clubhand", "Radial longitidinal meromelia", "Radial ray agenesis"]}
|
Susceptibility to respiratory infections associated with CD8 alpha chain mutation is a rare primary immunodeficiency due to a defect in adaptive immunity characterized by the absence of CD8+ T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity range from fatal respiratory insufficiency to mild or asymptomatic phenotypes.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Susceptibility to respiratory infections associated with CD8alpha chain mutation
|
c1837065
| 8,217 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169085
| 2021-01-23T18:59:51 |
{"mesh": ["C563824"], "omim": ["608957"], "umls": ["C1837065"], "icd-10": ["D84.8"], "synonyms": ["Familial CD8 deficiency"]}
|
Human disease caused by the bacteria Bordetella pertussis
Whooping cough
Other namesPertussis, 100-day cough
A young boy coughing due to pertussis.
SpecialtyInfectious disease
SymptomsRunny nose, fever, cough[1]
ComplicationsVomiting, broken ribs, very tired[1][2]
Duration~ 10 weeks[3]
CausesBordetella pertussis (spread through the air)[4]
Diagnostic methodNasopharyngeal swab[5]
PreventionPertussis vaccine[6]
TreatmentAntibiotics (if started early)[7]
Frequency16.3 million (2015)[8]
Deaths58,700 (2015)[9]
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease.[1][10] Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by weeks of severe coughing fits.[1] Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in.[1] The coughing may last for 10 or more weeks, hence the phrase "100-day cough".[3] A person may cough so hard that they vomit, break ribs, or become very tired from the effort.[1][2] Children less than one year old may have little or no cough and instead have periods where they do not breathe.[1] The time between infection and the onset of symptoms is usually seven to ten days.[11] Disease may occur in those who have been vaccinated, but symptoms are typically milder.[1]
Pertussis is caused by the bacterium Bordetella pertussis.[4] It is spread easily through the coughs and sneezes of an infected person.[4][12] People are infectious from the start of symptoms until about three weeks into the coughing fits.[7] Those treated with antibiotics are no longer infectious after five days.[7] Diagnosis is by collecting a sample from the back of the nose and throat.[5] This sample can then be tested by either culture or by polymerase chain reaction.[5]
Prevention is mainly by vaccination with the pertussis vaccine.[6] Initial immunization is recommended between six and eight weeks of age, with four doses to be given in the first two years of life.[13] Protection from pertussis decreases over time, so additional doses of vaccine are often recommended for older children and adults.[14] Antibiotics may be used to prevent the disease in those who have been exposed and are at risk of severe disease.[15] In those with the disease, antibiotics are useful if started within three weeks of the initial symptoms, but otherwise have little effect in most people.[7] In pregnant women and children less than one year old, antibiotics are recommended within six weeks of symptom onset.[7] Antibiotics used include erythromycin, azithromycin, clarithromycin, or trimethoprim/sulfamethoxazole.[7] Evidence to support interventions for the cough, other than antibiotics, is poor.[16] About 50% of infected children less than a year old require hospitalization and nearly 0.5% (1 in 200) die.[1][2]
An estimated 16.3 million people worldwide were infected in 2015.[8] Most cases occur in the developing world, and people of all ages may be affected.[6][16] In 2015, pertussis resulted in 58,700 deaths – down from 138,000 deaths in 1990.[9][17] Outbreaks of the disease were first described in the 16th century.[11] The bacterium that causes the infection was discovered in 1906.[11] The pertussis vaccine became available in the 1940s.[11]
## Contents
* 1 Signs and symptoms
* 1.1 Incubation period
* 2 Cause
* 2.1 Spread from other animals
* 3 Mechanism
* 4 Diagnosis
* 4.1 Based on symptoms
* 4.2 Lab tests
* 4.3 Differential diagnosis
* 5 Prevention
* 5.1 Vaccine
* 6 Treatment
* 7 Prognosis
* 8 Epidemiology
* 8.1 US outbreaks
* 9 History
* 9.1 Discovery
* 9.2 Vaccine
* 10 References
* 11 External links
## Signs and symptoms[edit]
Play media
A boy with pertussis
The classic symptoms of pertussis are a paroxysmal cough, inspiratory whoop, and fainting, or vomiting after coughing.[18] The cough from pertussis has been documented to cause subconjunctival hemorrhages, rib fractures, urinary incontinence, hernias, and vertebral artery dissection.[18] Violent coughing can cause the pleura to rupture, leading to a pneumothorax. Vomiting after a coughing spell or an inspiratory whooping sound on coughing, almost doubles the likelihood that the illness is pertussis. The absence of a paroxysmal cough or posttussive emesis, though, makes it almost half as likely.[18]
The illness usually starts with mild respiratory symptoms include mild coughing, sneezing, or a runny nose (known as the catarrhal stage). After one to two weeks, the coughing classically develops into uncontrollable fits, sometimes followed by a high-pitched "whoop" sound, as the person tries to inhale. About 50% of children and adults "whoop" at some point in diagnosed pertussis cases during the paroxysmal stage.
This stage usually lasts two to eight weeks, or sometimes longer. A gradual transition then occurs to the convalescent stage, which usually lasts one to four weeks. This stage is marked by a decrease in paroxysms of coughing, although paroxysms may occur with subsequent respiratory infection for many months after the onset of pertussis.[19]
Symptoms of pertussis can be variable, especially between immunized and non-immunized people. Those that are immunized can present with a more mild infection; they may only have the paroxysmal cough for a couple of weeks, and it may lack the "whooping" characteristic.[20] Although immunized people have a milder form of the infection, they can spread the disease to others who are not immune.[20]
### Incubation period[edit]
The time between exposure and the development of symptoms is on average 7–14 days (range 6–20 days),[21] rarely as long as 42 days.[22]
## Cause[edit]
Pertussis is caused by the bacterium Bordetella pertussis. It is an airborne disease (through droplets) that spreads easily through the coughs and sneezes of an infected person.[4]
### Spread from other animals[edit]
Uncertainties have existed of B. pertussis and whooping cough as a zoonotic disease since around 1910[23][24] but in the 1930s, knowledge was gained that the bacteria lost their virulent power when repeatedly spread on agar media. This explained the difficulties to reproduce results from different studies as the pre-inoculating handlings of the bacteria were not standardized among scientists.[25]
Today it is established that at least some primate species are highly susceptible to B. pertussis and develop clinical whooping cough in high incidence when exposed to low inoculation doses.[26][27] The bacteria may be present in wild animal populations, but this is not confirmed by laboratory diagnosis, although whooping cough is known among wild gorillas.[28] Several zoos also have a long-standing custom of vaccinating their primates against whooping cough.[29]
## Mechanism[edit]
After the bacteria are inhaled, they initially adhere to the ciliated epithelium in the nasopharynx. Surface proteins of B. pertussis, including filamentous hemaglutinin and pertactin, mediate attachment to the epithelium. The bacteria then multiply.[30][31] In infants, who experience more severe disease, the bacteria spread down to the lungs.[31]
The bacteria secretes a number of toxins. Tracheal cytotoxin, a fragment of peptidoglycan, kills ciliated epithelial cells and thereby inhibits the mucociliary elevator by which mucus and debris are removed.[32] TCT may contribute to the cough characteristic of pertussis.[33] The cough may also be caused by a yet-to-be identified "cough toxin".[34] Pertussis toxin causes lymphocytosis by an unknown mechanism. The elevated number of white blood cells leads to pulmonary hypertension, a major cause of death by pertussis.[32][31] In infants who develop encephalopathy, cerebral hemorrhage and cortical atrophy occur, likely due to hypoxia.[31]
## Diagnosis[edit]
Gram stain of Bordetella pertussis
### Based on symptoms[edit]
A physician's overall impression is most effective in initially making the diagnosis.[35] Single factors are much less useful.[35] In adults with a cough of less than 8 weeks, vomiting after coughing or a "whoop" is supportive.[36] If there are no bouts of coughing or there is a fever the diagnosis is unlikely.[36] In children who have a cough of less than 4 weeks vomiting after coughing is somewhat supportive but not definitive.[36]
### Lab tests[edit]
Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on a nutrient medium (Bordet-Gengou medium), polymerase chain reaction (PCR), direct fluorescent antibody (DFA), and serological methods (e.g. complement fixation test).[37] The bacteria can be recovered from the person only during the first three weeks of illness, rendering culturing and DFA useless after this period, although PCR may have some limited usefulness for an additional three weeks.
Serology may be used for adults and adolescents who have already been infected for several weeks to determine whether antibody against pertussis toxin or another virulence factor of B. pertussis is present at high levels in the blood of the person.[38]
### Differential diagnosis[edit]
A similar, milder disease is caused by B. parapertussis.[39]
## Prevention[edit]
The primary method of prevention for pertussis is vaccination.[40] Evidence is insufficient to determine the effectiveness of antibiotics in those who have been exposed, but are without symptoms.[41] Preventive antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).[6]
### Vaccine[edit]
Pertussis vaccines are effective at preventing illness[42] and are recommended for routine use by the World Health Organization[43] and the United States Centers for Disease Control and Prevention.[44] The vaccine saved an estimated half a million lives in 2002.[43]
The multicomponent acellular pertussis vaccine is 71–85% effective, with greater effectiveness against more severe strains.[42] However, despite widespread vaccination, pertussis has persisted in vaccinated populations and is today "one of the most common vaccine-preventable diseases in Western countries".[45] The 21st-century resurgences in pertussis infections is attributed to a combination of waning immunity and bacterial mutations that elude vaccines.[45][46]
Immunization does not confer lifelong immunity; a 2011 CDC study indicated that protection may only last three to six years. This covers childhood, which is the time of greatest exposure and greatest risk of death from pertussis.[18][47]
An effect of widespread immunization on society has been the shift of reported infections from children aged 1–9 years to infants, adolescents, and adults, with adolescents and adults acting as reservoirs for B. pertussis and infecting infants who have had fewer than three doses of vaccine.[48]
Infection induces incomplete natural immunity that wanes over time.[49] A 2005 study said estimates of the duration of infection-acquired immunity range from 7 to 20 years and the different results could be the result of differences in levels of circulating B. pertussis, surveillance systems, and case definitions used. The study said protective immunity after vaccination wanes after 4–12 years.[50] One study suggested that the availability of vaccine exemptions increases the number of pertussis cases.[51]
Some studies have suggested that while acellular pertussis vaccines are effective at preventing the disease, they have a limited impact on infection and transmission, meaning that vaccinated people could spread pertussis even though they may have only mild symptoms or none at all.[52][53] Pertussis infection in these persons may be asymptomatic, or present as illness ranging from a mild cough to classic pertussis with persistent cough (i.e., lasting more than 7 days). Even though the disease may be milder in older persons, those who are infected may transmit the disease to other susceptible persons, including unimmunized or incompletely immunized infants. Older persons are often found to have the first case in a household with multiple pertussis cases, and are often the source of infection for children.[19]
## Treatment[edit]
The antibiotics erythromycin, clarithromycin, or azithromycin are typically the recommended treatment.[41] Newer macrolides are frequently recommended due to lower rates of side effects.[6] Trimethoprim-sulfamethoxazole (TMP/SMX) may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.[6]
A reasonable guideline is to treat people age >1 year within 3 weeks of cough onset and infants age <1 year and pregnant women within 6 weeks of cough onset. If the person is diagnosed late, antibiotics will not alter the course of the illness, and even without antibiotics, they should no longer be spreading pertussis.[6] When used early, antibiotics decrease the duration of infectiousness, and thus prevent spread.[6] Short-term antibiotics (azithromycin for 3–5 days) are as effective as long-term treatment (erythromycin 10–14 days) in eliminating B. pertussis with fewer and less severe side effects.[41]
People with pertussis are most infectious during the first two weeks following the onset of symptoms.[54]
Effective treatments of the cough associated with this condition have not been developed.[55] The use of over the counter cough medications is discouraged and has not been found helpful.[20]
## Prognosis[edit]
Disability-adjusted life year for pertussis per 100,000 inhabitants as of 2004.
No data
Less than 50
50–100
100–150
150–200
200–250
250–300
300–350
350–400
400–450
450–500
500–550
More than 550
While most healthy older children and adults fully recover, infection in newborns is particularly severe. Pertussis is fatal in an estimated 0.5% of US infants under one year of age.[56] First-year infants are also more likely to develop complications, such as: apneas (31%), pneumonia (12%), seizures (0.6%) and encephalopathy (0.15%).[56] This may be due to the ability of the bacterium to suppress the immune system.[57]
## Epidemiology[edit]
Whooping cough deaths per million persons in 2012
0–0.9
1–1.9
2–3
4–4.9
5–5.9
6–32
33–38
39–44
45–79
Worldwide, whooping cough affects around 16 million people yearly.[16] One estimate for 2013 stated it resulted in about 61,000 deaths – down from 138,000 deaths in 1990.[17] Another estimated 195,000 child deaths yearly from the disease worldwide.[58] This is despite generally high coverage with the DTP and DTaP vaccines. Pertussis is one of the leading causes of vaccine-preventable deaths worldwide.[59] About 90% of all cases occur in developing countries.[59]
Before vaccines, an average of 178,171 cases was reported in the U.S., with peaks reported every two to five years; more than 93% of reported cases occurred in children under 10 years of age. The actual incidence was likely much higher. After vaccinations were introduced in the 1940s, pertussis incidence fell dramatically to approximately 1,000 by 1976. Incidence rates have increased since 1980. In 2015, rates in the United States were 20,762 people.[60]
Pertussis is the only vaccine-preventable disease that is associated with increasing deaths in the U.S. The number of deaths increased from four in 1996 to 17 in 2001, almost all of which were infants under one year.[61] In Canada, the number of pertussis infections has varied between 2,000 and 10,000 reported cases each year over the last ten years, and it is the most common vaccine-preventable illness in Toronto.[62]
In 2009 Australia reported an average of 10,000 cases a year, and the number of cases had increased.[63] In the U.S. pertussis in adults has increased significantly since about 2004.[64]
In 2017, India had a reported 23,766 reported pertussis cases, making it one of the highest reported number of cases of the year.[65] Other countries, such as Germany, had reported 16,183 cases, while Australia and China had a reported number of 12,114 and 10,390 pertussis cases.[65]
### US outbreaks[edit]
An epidemiologist tests blood samples for pertussis during a 2010 outbreak.
In 2010 ten infants in California died, and health authorities declared an epidemic encompassing 9,120 cases.[66][67] They found that doctors had failed to correctly diagnose the infants' condition during several visits.[68] Statistical analysis identified significant overlap in communities with a cluster of nonmedical child exemptions and cases. The number of exemptions varied widely among communities, but tended to be highly clustered. In some schools, more than three-quarters of parents filed for vaccination exemptions. The data suggest vaccine refusal based on nonmedical reasons and personal belief exacerbated the outbreak. Other factors included reduced duration of immunity following the acellular vaccine and, the fact that most vaccinated adults and older children had not received a booster shot.[69][70]
In April and May 2012 pertussis was declared to be at epidemic levels in Washington, with 3,308 cases.[71][72][73] In December 2012 Vermont declared an epidemic of 522 cases.[74] Wisconsin had the highest incidence rate, with 3,877 cases, although it did not make an official epidemic declaration.[73]
## History[edit]
### Discovery[edit]
B. pertussis was discovered in 1906 by Jules Bordet and Octave Gengou, who also developed the first serology and vaccine. Efforts to develop an inactivated whole-cell vaccine began soon after B. pertussis was cultured that year. In the 1920s, Louis W. Sauer developed a weak vaccine for whooping cough at Evanston Hospital (Evanston, IL). In 1925 Danish physician Thorvald Madsen was the first to test a whole-cell vaccine on a wide scale.[75] Madsen used the vaccine to control outbreaks in the Faroe Islands in the North Sea.
### Vaccine[edit]
In 1932 an outbreak of whooping cough hit Atlanta, Georgia, prompting pediatrician Leila Denmark to begin her study of the disease. Over the next six years her work was published in the Journal of the American Medical Association, and in partnership with Emory University and Eli Lilly & Company, she developed the first pertussis vaccine.[76] In 1942 American scientists Grace Eldering, Loney Gordon, and Pearl Kendrick combined the whole-cell pertussis vaccine with diphtheria and tetanus toxoids to generate the first DTP combination vaccine.[77] To minimize the frequent side effects caused by the pertussis component, Japanese scientist Yuji Sato developed an acellular vaccine consisting of purified haemagglutinins (HAs: filamentous strep throat and leukocytosis-promoting-factor HA), which are secreted by B. pertussis. Sato's acellular pertussis vaccine was used in Japan starting in 1981.[78] Later versions of the acellular vaccine in other countries consisted of additional defined components of B. pertussis and were often part of the DTaP combination vaccine.
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76. ^ "Changing the Face of Medicine | Dr. Leila Alice Daughtry Denmark". www.nlm.nih.gov. Archived from the original on 21 March 2015. Retrieved 3 February 2016.
77. ^ Bannink J. "Finding aid for the Michigan women and the whooping cough vaccine collection[s]" (PDF). Archived (PDF) from the original on 5 February 2015. Cite journal requires `|journal=` (help)
78. ^ Sato Y, Kimura M, Fukumi H (January 1984). "Development of a pertussis component vaccine in Japan". Lancet. 1 (8369): 122–6. doi:10.1016/S0140-6736(84)90061-8. PMID 6140441. S2CID 23621152.
## External links[edit]
Classification
D
* ICD-10: A37
* ICD-9-CM: 033
* MeSH: D014917
* DiseasesDB: 1523
External resources
* MedlinePlus: 001561
* eMedicine: emerg/394 ped/1778
* Patient UK: Whooping cough
* Orphanet: 1489
Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app.
Wikimedia Commons has media related to Pertussis.
* Pertussis at Todar's Online Textbook of Bacteriology
* PBS NOVA – Vaccines: Calling The Shots
* "Whooping Cough". MedlinePlus. U.S. National Library of Medicine.
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
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fever
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* Rickettsia rickettsii
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Burkholderiales
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Authority control
* NDL: 00563843
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Whooping cough
|
c0006015
| 8,218 |
wikipedia
|
https://en.wikipedia.org/wiki/Whooping_cough
| 2021-01-18T18:57:24 |
{"gard": ["8692"], "mesh": ["D001885", "D014917"], "umls": ["C0006015"], "icd-9": ["033"], "icd-10": ["A37"], "orphanet": ["1489"], "wikidata": ["Q134859"]}
|
Eto and Kitagawa (1970) described a disorder with features of malabsorption of lipid, vomiting, growth failure, and adrenal calcification. Hypolipoproteinemia and acanthocytosis suggest this is an entity distinct from Wolman disease (278000).
Radiology \- Adrenal calcification Growth \- Growth failure Lab \- Hypolipoproteinemia \- Acanthocytosis GI \- Malabsorption of lipid \- Vomiting Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
WOLMAN DISEASE WITH HYPOLIPOPROTEINEMIA AND ACANTHOCYTOSIS
|
c1848436
| 8,219 |
omim
|
https://www.omim.org/entry/278100
| 2019-09-22T16:21:09 |
{"mesh": ["C564736"], "omim": ["278100"]}
|
A number sign (#) is used with this entry because of evidence that Shohat-type spondyloepimetaphyseal dysplasia (SEMDSH) is caused by homozygous mutation in the DDRGK1 gene (616177) on chromosome 20p13.
Description
Shohat-type spondyloepimetaphyseal dysplasia (SEMDSH) is a chondrodysplasia characterized by vertebral, epiphyseal, and metaphyseal abnormalities, including scoliosis with vertebral compression fractures, flattened vertebral bodies, and hypomineralization of long bones. Affected individuals may exhibit a small trunk, short neck, small limbs, joint laxity, bowlegs, and/or abdominal distention with hepatosplenomegaly (summary by Egunsola et al., 2017).
Clinical Features
Shohat et al. (1993) described 3 patients, 2 brothers and a son of their male cousin, with spondyloepimetaphyseal dysplasia (SEMD). All 3 boys had severe short stature, short neck, small chest, distended abdomen, lumbar lordosis, and marked genu varum. Radiologic manifestations during the first months of life were similar to those in achondroplasia (100800). After 1 year of age, significant metaphyseal changes (widened flared metaphyses with irregularity and ossification defects) and delayed ossification of epiphyses were evident. Other forms of SEMD (see 184250, 271640) were excluded. Egunsola et al. (2017) provided follow-up on this family. At age 18 years, the cousin's son (patient 1) required a lifesaving tracheostomy during orthopedic surgery due to a narrowed trachea, and 1 of the 2 brothers (patient 3) died due to this surgical complication. At age 26, patient 1 had hoarseness due to his severely narrowed larynx and bronchi, as well as joint pain.
Figuera et al. (1994), who reported a Mexican boy with the same type of SEMD, proposed the name 'spondyloepimetaphyseal dysplasia, Shohat type.'
Egunsola et al. (2017) studied 4 Jewish families of Iraqi descent with SEMDSH, including the family originally described by Shohat et al. (1993) (family 1). The 4 affected individuals in the 3 new families were diagnosed with very short limbs in utero, and at birth showed vertebral and long-bone defects similar to those observed in family 1. In 1 of the families (family 4), an affected female (patient 5) had severe scoliosis, vertebral compression fractures, platyspondyly, broadened hypomineralized metaphyses, and hypomineralized epiphyses, as well as a narrow trachea and severe upper airway obstruction requiring a tracheostomy and continuous positive airway pressure (CPAP) therapy while sleeping. Her affected brother (patient 4) died during a surgical procedure due to a narrowed trachea.
Inheritance
Shohat et al. (1993) suggested that spondyloepimetaphyseal dysplasia in the family they reported had autosomal recessive inheritance.
Molecular Genetics
In 2 Jewish families of Iraqi descent with SEMDSH (families 1 and 2), one of which was the family originally reported by Shohat et al. (1993), Egunsola et al. (2017) performed whole-exome sequencing and identified homozygosity for a splice site mutation in the DDRGK1 gene (616177.0001) that segregated fully with disease in both families. Sanger sequencing in 2 more Jewish families of Iraqi descent with SEMDSH revealed homozygosity for the same DDRGK1 splice site mutation in 2 affected individuals, suggesting that this variant represents a founder mutation.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, severe disproportionate HEAD & NECK Mouth \- Thin lips Neck \- Short neck RESPIRATORY Airways \- Tracheal narrowing (in some patients) CHEST External Features \- Bell-shaped chest Ribs Sternum Clavicles & Scapulae \- Short ribs \- Splayed ribs ABDOMEN External Features \- Distended abdomen Liver \- Mild hepatomegaly Spleen \- Mild splenomegaly SKELETAL \- Spondyloepimetaphyseal dysplasia \- Joint laxity Spine \- Severe lumbar lordosis \- Severe scoliosis (rare) \- Platyspondyly (infancy) \- Central vertebral hypoplasia (infancy) \- Squared vertebrae (childhood) \- Mild interpedicular narrowing Pelvis \- Flat acetabulae \- Coxa vara \- Short ilium \- Narrowed greater sciatic notch Limbs \- Short limbs \- Genu varum \- Fibular overgrowth \- Metaphyseal irregularities \- Metaphyseal hypomineralization \- Epiphyseal ossification delay \- Flared, widened metaphyses \- Short femoral neck VOICE \- Hoarseness (in some patients) MISCELLANEOUS \- Waddling gate \- Tracheal narrowing may result in fatal upper airway obstruction MOLECULAR BASIS \- Caused by mutation in the DDRGK domain-containing protein 1 gene (DDRGK1, 616177.0001 ) ▲ 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
|
SPONDYLOEPIMETAPHYSEAL DYSPLASIA, SHOHAT TYPE
|
c1865185
| 8,220 |
omim
|
https://www.omim.org/entry/602557
| 2019-09-22T16:13:35 |
{"mesh": ["C566523"], "omim": ["602557"], "orphanet": ["93352"], "synonyms": ["Alternative titles", "SEMD, SHOHAT TYPE"]}
|
Salicylate poisoning
Other namesSalicylism, salicylate toxicity, aspirin poisoning, aspirin toxicity, aspirin overdose
A skeletal structural formula for aspirin.
SpecialtyEmergency medicine
SymptomsRinging in the ears, nausea, abdominal pain, fast breathing rate[1]
ComplicationsSwelling of the brain or lungs, seizures, low blood sugar, cardiac arrest[1]
Diagnostic methodEarly: Slightly elevated blood aspirin levels ~ 2.2 mmol/L (30 mg/dL, 300 mg/L), respiratory alkalosis[1]
Late: Metabolic acidosis[1]
Differential diagnosisSepsis, heart attack, agitation[1]
PreventionChild-resistant packaging, low number of pills per package[1]
TreatmentActivated charcoal, intravenous sodium bicarbonate with dextrose and potassium chloride, dialysis[2]
Prognosis~1% risk of death[3]
Frequency> 20,000 per year (US)[1]
Salicylate poisoning, also known as aspirin poisoning, is the acute or chronic poisoning with a salicylate such as aspirin.[1] The classic symptoms are ringing in the ears, nausea, abdominal pain, and a fast breathing rate.[1] Early on, these may be subtle, while larger doses may result in fever.[1][4] Complications can include swelling of the brain or lungs, seizures, low blood sugar, or cardiac arrest.[1]
While usually due to aspirin, other possible causes include oil of wintergreen and bismuth subsalicylate.[2] Excess doses can be either on purpose or accidental.[1] Small amounts of oil of wintergreen can be toxic.[2] Diagnosis is generally based on repeated blood tests measuring aspirin levels and blood gases.[1] While a type of graph has been created to try to assist with diagnosis, its general use is not recommended.[1] In overdose maximum blood levels may not occur for more than 12 hours.[2]
Efforts to prevent poisoning include child-resistant packaging and a lower number of pills per package.[1] Treatment may include activated charcoal, intravenous sodium bicarbonate with dextrose and potassium chloride, and dialysis.[2] Giving dextrose may be useful even if the blood sugar is normal.[2] Dialysis is recommended in those with kidney failure, decreased level of consciousness, blood pH less than 7.2, or high blood salicylate levels.[2] If a person requires intubation, a fast respiratory rate may be required.[1]
The toxic effects of salicylates have been described since at least 1877.[5] In 2004, more than 20,000 cases with 43 deaths were reported in the United States.[1] About 1% of those with an acute overdose die, while chronic overdoses may have worse outcomes.[3] Older people are at higher risks of toxicity for any given dose.[5]
## Contents
* 1 Signs and symptoms
* 1.1 Severity
* 2 Pathophysiology
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 5.1 Intravenous fluids
* 5.2 Dialysis
* 6 Epidemiology
* 7 History
* 8 See also
* 9 References
* 10 External links
## Signs and symptoms[edit]
Main symptoms of aspirin overdose[6]
Salicylate toxicity has potentially serious consequences, sometimes leading to significant morbidity and death. Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, ringing in the ears, and dizziness. More significant signs and symptoms occur in more severe poisonings and include high body temperature, fast breathing rate, respiratory alkalosis, metabolic acidosis, low blood potassium, low blood glucose, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.[7]
### Severity[edit]
The severity of toxicity depends on the amount of aspirin taken.
Severity Mild (150 mg/kg) Moderate (150–300 mg/kg) Severe (300–500 mg/kg)
Toxicity No toxicity expected Mild to moderate toxicity expected Life-threatening toxicity expected
Symptoms Nausea, vomiting, dizziness Nausea, vomiting, ringing in the ears, headache, confusion, hyperventilation, tachycardia, fever Delirium, hallucinations, seizures, coma, respiratory arrest
## Pathophysiology[edit]
High levels of salicylates stimulate peripheral chemoreceptors and the central respiratory centers in the medulla causing increased ventilation and a respiratory alkalosis.[8] The increased pH secondary to hyperventilation with respiratory alkalosis causes an increase in lipolysis and ketogenesis which causes the production of lactate and organic keto-acids (such as beta-hydroxybutyrate).[8] The accumulation of these organic acids can cause an acidosis with an increased anion-gap as well as a decreased buffering capacity of the body.[8] Salicylate toxicity also causes an uncoupling of oxidative phosphorylation and a decrease in citric acid cycle activity in the mitochondria.[8] This decrease in aerobic production of adenosine triphosphate (ATP) is accompanied by an increase in anaerobic production of ATP through glycolysis which leads to glycogen depletion and hypoglycemia.[8]The inefficient ATP production through anaerobic metabolism causes the body to shift to a catabolic predominant mode for energy production which consists of increased oxygen consumption, increased heat production (often manifesting as sweating), liver glycogen utilization and increased carbon dioxide production.[8] This increased catabolism accompanied by hyperventilation can lead to severe insensible water losses, dehydration and hypernatremia.[8]
Acute aspirin or salicylates overdose or poisoning can cause initial respiratory alkalosis though metabolic acidosis ensues thereafter. The acid-base, fluid, and electrolyte abnormalities observed in salicylate toxicity can be grouped into three broad phases:
* Phase I is characterized by hyperventilation resulting from direct respiratory center stimulation, leading to respiratory alkalosis and compensatory alkaluria. Potassium and sodium bicarbonate are excreted in the urine. This phase may last as long as 12 hours.[9]
* Phase II is characterized by paradoxic aciduria in the presence of continued respiratory alkalosis occurs when sufficient potassium has been lost from the kidneys. This phase may begin within hours and may last 12–24 hours.[9]
* Phase III is characterized by dehydration, hypokalemia, and progressive metabolic acidosis. This phase may begin 4–6 hours after ingestion in a young infant[10] or 24 hours or more after ingestion in an adolescent or adult.[9]
## Diagnosis[edit]
The acutely toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass.[11] Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 and 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg.[12] Chronic toxicity may occur following doses of 100 mg/kg per day for two or more days.[12]
Monitoring of biochemical parameters such as electrolytes and solutes, liver and kidney function, urinalysis, and complete blood count is undertaken along with frequent checking of salicylate and blood sugar levels. Arterial blood gas assessments typically find respiratory alkalosis early in the course of the overdose due to hyperstimulation of the respiratory center, and may be the only finding in a mild overdose. An anion-gap metabolic acidosis occurs later in the course of the overdose, especially if it is a moderate to severe overdose, due to the increase in protons (acidic contents) in the blood.
The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels generally range from 30–100 mg/l (3–10 mg/dl) after usual therapeutic doses, 50–300 mg/l in patients taking high doses, and 700–1400 mg/l following acute overdose.[13] Patients may undergo repeated testing until their peak plasma salicylate level can be estimated.[14] Optimally, plasma levels should be assessed four hours after ingestion and then every two hours after that to allow calculation of the maximum level, which can then be used as a guide to the degree of toxicity expected.[15] Patients may also be treated according to their individual symptoms.
## Prevention[edit]
A bottle of aspirin with a child-resistant cap bearing the instruction "push down and turn to open"
Efforts to prevent poisoning include child-resistant packaging and a lower number of pills per package.[1]
## Treatment[edit]
There is no antidote for salicylate poisoning.[8] Initial treatment of an overdose involves resuscitation measures such as maintaining an adequate airway and adequate circulation followed by gastric decontamination by administering activated charcoal, which adsorbs the salicylate in the gastrointestinal tract.[8] Stomach pumping is no longer routinely used in the treatment of poisonings, but is sometimes considered if the patient has ingested a potentially lethal amount less than one hour before presentation.[16] Inducing vomiting with syrup of ipecac is not recommended.[11] Repeated doses of activated charcoal have been proposed to be beneficial in cases of salicylate poisoning,[17] especially in ingestion of enteric coated and extended release salicylic acid formulations which are able to remain in the gastrointestinal (GI) tract for longer periods of time.[8] Repeated doses of activated charcoal are also useful to re-adsorb salicylates in the GI tract that may have desorbed from the previous administration of activated charcoal.[8] The initial dose of activated charcoal is most useful if given within 2 hours of initial ingestion.[8] Contraindications to the use of activated charcoal include altered mental status (due to the risk of aspiration), GI bleeding (often due to salicylates) or poor gastric motility.[8] Whole bowel irrigation using the laxative polyethylene glycol can be useful to induce the gastrointestinal elimination of salicylates, particularly if there is partial or diminished response to activated charcoal.[8]
Alkalinization of the urine and plasma, by giving a bolus of sodium bicarbonate then adding sodium bicarbonate to maintenance fluids, is an effective method to increase the clearance of salicylates from the body.[8] Alkalinization of the urine causes salicylates to be trapped in renal tubules in their ionized form and then readily excreted in the urine. Alkalinization of the urine increases urinary salicylate excretion by 18 fold.[8] Alkalinization of the plasma decreases the lipid soluble form of salicylates facilitating movement out of the central nervous system.[8] Oral sodium bicarbonate is contra-indicated in salicylate toxicity as it can cause dissociation of salicylate tablets in the GI tract and subsequent increased absorption.[8]
### Intravenous fluids[edit]
Intravenous fluids containing dextrose such as dextrose 5% in water (D5W) are recommended to keep a urinary output between 1 and 1.5 millilitres per kilogram per hour.[8]
Sodium bicarbonate is given in a significant aspirin overdose (salicylate level greater than 35 mg/dl 6 hours after ingestion) regardless of the serum pH, as it enhances elimination of aspirin in the urine. It is given until a urine pH between 7.5 and 8.0 is achieved.[18]
### Dialysis[edit]
Hemodialysis can be used to enhance the removal of salicylate from the blood, usually in those who are severely poisoned. Examples of severe poisoning include people with high salicylate blood levels: 7.25 mmol/l (100 mg/dl) in acute ingestions or 40 mg/dl in chronic ingestions,[18] significant neurotoxicity (agitation, coma, convulsions), kidney failure, pulmonary edema, or cardiovascular instability.[14] Hemodialysis also has the advantage of restoring electrolyte and acid-base abnormalities while removing salicylate.[19]
Salicylic acid has a small size (low molecular mass), has a low volume of distribution (is more water soluble), has low tissue binding and is largely free (and not protein bound) at toxic levels in the body; all of which make it easily removable from the body by hemodialysis.[8]
Indication for dialysis:
1. Salicylate level higher than 90 mg/dL[8]
2. Severe acid base imbalance
3. Severe cardiac toxicity
4. Acute respiratory distress syndrome[8]
5. Cerebral involvement/ neurological signs and symptoms
6. Rising serum salicylate level despite alkalinization/multidose activated charcoal, or people in which standard approaches to treatment ave failed[8]
7. Unable to tolerate fluids with fluid overload
## Epidemiology[edit]
Acute salicylate toxicity usually occurs after an intentional ingestion by younger adults, often with a history of psychiatric disease or previous overdose, whereas chronic toxicity usually occurs in older adults who experience inadvertent overdose while ingesting salicylates therapeutically over longer periods of time.[8]
During the latter part of the 20th century, the number of poisonings from salicylates declined, mainly because of the increased popularity of other over-the-counter analgesics such as paracetamol (acetaminophen). Fifty-two deaths involving single-ingredient aspirin were reported in the United States in 2000; however, in all but three of these cases, the reason for the ingestion of lethal doses was intentional—predominantly suicidal.[20]
## History[edit]
Aspirin poisoning has controversially been cited as a possible cause of the high mortality rate during the 1918 flu pandemic, which killed 50 to 100 million people.[21]
## See also[edit]
* NSAID hypersensitivity reactions
* Reye syndrome
* Salicylate sensitivity
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r O'Malley, GF (May 2007). "Emergency department management of the salicylate-poisoned patient". Emergency Medicine Clinics of North America. 25 (2): 333–46, abstract viii. doi:10.1016/j.emc.2007.02.012. PMID 17482023.
2. ^ a b c d e f g Walls, Ron (2017). Rosens Emergency Medicine Concepts and Clinical Practice (9th ed.). Elsevier. p. X. ISBN 978-0323354790.
3. ^ a b McNeil Consumer & Specialty Pharmaceuticals (2002). "Assessment of Safety of aspirin and other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)". FDA. Archived from the original on 14 May 2017. Retrieved 27 June 2017.
4. ^ Brenner, George M.; Stevens, Craig (2012). Pharmacology E-Book: with STUDENT CONSULT Online Access (4 ed.). Elsevier Health Sciences. p. 319. ISBN 978-1455702787. Archived from the original on 2017-08-18.
5. ^ a b Roland, Peter S.; Rutka, John A. (2004). Ototoxicity. PMPH-USA. p. 28. ISBN 9781550092639. Archived from the original on 10 September 2017. Retrieved 27 June 2017.
6. ^ MedlinePlus > Aspirin Archived 2009-07-20 at the Wayback Machine Last Reviewed - 02/01/2009.
7. ^ Thisted, B; Krantz, T; Strøom, J; Sørensen, MB (May 1987). "Acute salicylate self-poisoning in 177 consecutive patients treated in ICU". Acta Anaesthesiologica Scandinavica. 31 (4): 312–6. doi:10.1111/j.1399-6576.1987.tb02574.x. ISSN 0001-5172. PMID 3591255. S2CID 21769646.
8. ^ a b c d e f g h i j k l m n o p q r s t u v w x Palmer, Biff F.; Clegg, Deborah J. (25 June 2020). "Salicylate Toxicity". New England Journal of Medicine. 382 (26): 2544–2555. doi:10.1056/NEJMra2010852. PMID 32579814.
9. ^ a b c Salicylate Toxicity at eMedicine
10. ^ "Drugs and Lactation Database (LactMed)". toxnet.nlm.nih.gov. Archived from the original on 2017-09-10. This article incorporates text from this source, which is in the public domain.
11. ^ a b Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, Caravati EM, Nelson LS, Olson KR, Cobaugh DJ, Scharman EJ, Woolf AD, Troutman WG (2007). "Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management". Clinical Toxicology. 45 (2): 95–131. doi:10.1080/15563650600907140. PMID 17364628.
12. ^ a b Temple, AR (February 1981). "Acute and chronic effects of aspirin toxicity and their treatment". Archives of Internal Medicine. 141 (3 Spec No): 364–9. doi:10.1001/archinte.141.3.364. ISSN 0003-9926. PMID 7469627.
13. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 20-23.
14. ^ a b Dargan, PI; Wallace, CI; Jones, AL (May 2002). "An evidenced based flowchart to guide the management of acute salicylate (aspirin) overdose". Emergency Medicine Journal. 19 (3): 206–9. doi:10.1136/emj.19.3.206. ISSN 1472-0205. PMC 1725844. PMID 11971828.
15. ^ Meredith TJ, Vale JA (1986). "Non-narcotic analgesics. Problems of overdosage". Drugs. 32 (Suppl 4): 117–205. doi:10.2165/00003495-198600324-00013. ISSN 0012-6667. PMID 3552583. S2CID 40459545.
16. ^ Vale JA, Kulig K (2004). "Position paper: gastric lavage". Journal of Toxicology: Clinical Toxicology. 42 (7): 933–43. doi:10.1081/CLT-200045006. PMID 15641639. S2CID 29957973.
17. ^ Hillman, RJ; Prescott, LF (Nov 1985). "Treatment of salicylate poisoning with repeated oral charcoal". British Medical Journal (Clinical Research Ed.). 291 (6507): 1472. doi:10.1136/bmj.291.6507.1472. ISSN 0267-0623. PMC 1418067. PMID 3933714.
18. ^ a b Marx, John (2006). Rosen's emergency medicine: concepts and clinical practice. Mosby/Elsevier. p. 2342. ISBN 978-0-323-02845-5.
19. ^ Gaudreault, P; Temple, AR; Lovejoy Fh, FH (October 1982). "The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison". Pediatrics. 70 (4): 566–9. ISSN 0031-4005. PMID 7122154.
20. ^ Litovitz, TL; Klein-Schwartz, W; White, S; Cobaugh, DJ; Youniss, J; Omslaer, JC; Drab, A; Benson, BE (Sep 2001). "2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System". The American Journal of Emergency Medicine. 19 (5): 337–95. doi:10.1053/ajem.2001.25272. ISSN 0735-6757. PMID 11555795.
21. ^ Starko, KM (1 November 2009). "Salicylates and pandemic influenza mortality, 1918-1919 pharmacology, pathology, and historic evidence". Clinical Infectious Diseases. 49 (9): 1405–10. doi:10.1086/606060. PMID 19788357.
## External links[edit]
Classification
D
* ICD-10: T39.0
* ICD-9-CM: 965.1
External resources
* MedlinePlus: 002542
* eMedicine: emerg/514
Wikimedia Commons has media related to Aspirin.
* Reingardiene, D; Lazauskas, R (2006). "[Acute salicylate poisoning]". Medicina (Kaunas, Lithuania). 42 (1): 79–83. PMID 16467617.
* v
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1 including venoms, toxins, foodborne illnesses.
* Category
* Commons
* WikiProject
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Salicylate poisoning
|
c0161544
| 8,221 |
wikipedia
|
https://en.wikipedia.org/wiki/Salicylate_poisoning
| 2021-01-18T18:45:31 |
{"umls": ["C0161544"], "icd-9": ["965.1"], "icd-10": ["T39.0"], "wikidata": ["Q4808101"]}
|
Dermoid cysts are generally benign cystic tumors comprised predominantly of ectodermal elements. However, endodermal and mesodermal elements also may be included. These cysts are often filled with hair, skin, teeth, bones, neural tissue and sebaceous material. Plattner and Oxorn (1973) reported the presence of bilateral ovarian dermoid cysts in a mother and her only 2 daughters. This was the first report of such bilateral ovarian dermoid cysts occurring in consecutive generations of a family. These bilateral teratomas were surgically removed from the mother at age 22 and from both her daughters at age 23. The authors stated that the literature contained 18 cases in 6 families with a familial occurrence of dermoid cysts. Hecht et al. (1976) suggested that there may be an important genetic factor in ovarian teratomas. They observed affected grandmother and granddaughter and pointed to early onset, bilaterality (in 10 to 25% of patients) and the demonstrable genetic factor in mice (Stevens and Varnum, 1974) as supporting evidence.
Ovarian teratomas originate through failure of extrusion of the second polar body or refusion of it with the ovum, i.e., self-fertilization. This is a conclusion based on study of chromosome and biochemical polymorphism in teratoma cells (Linder et al., 1975). (Testicular teratomas may have a different origin.) Study of biochemical traits in cells of teratomas is a means of 'centromere mapping.' The farther from the centromere a given locus is situated, the higher is the proportion of teratomas from hosts heterozygous at that locus which will be heterozygous only. Loci close to the centromere will be homozygous; loci farther from the centromere will have a chance to be heterozygous, up to a limiting proportion of two-thirds. The last follows from the fact that a given chromatid has (at the four-strand stage) three other chromatids with which it can crossover. In a heterozygous host two of the three have a different allele at the given locus.
Deka et al. (1989) studied 62 host-teratoma pairs for chromosomal heteromorphisms and polymorphic DNA loci. Their findings contradicted the assumption of Linder et al. (1975) that teratomas originate only by meiosis II error; 27.3% originated by type I error and 15.9% by type IV error. In this study, 80% of teratomas were found to be useful for gene mapping, a contradiction to the report of Parrington et al. (1984) that most teratomas are not informative for mapping.
GU \- Ovarian teratoma 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
|
TERATOMA, OVARIAN
|
c0280131
| 8,222 |
omim
|
https://www.omim.org/entry/166950
| 2019-09-22T16:36:49 |
{"doid": ["5117"], "omim": ["166950"], "synonyms": ["Alternative titles", "DERMOID CYST, OVARIAN"]}
|
A rare form of autosomal dominant optic atrophy (ADOA) characterized by progressive and isolated visual loss in the first decade of life, decreased reflexes in the lower limbs and a mild cerebellar stance.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing 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 optic atrophy and peripheral neuropathy
|
None
| 8,223 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=250932
| 2021-01-23T17:04:38 |
{"icd-10": ["H47.2"]}
|
Keratoderma
SpecialtyDermatology
Keratoderma is a hornlike skin condition.[1]
## Contents
* 1 Classification
* 1.1 Congenital
* 1.2 Acquired
* 2 See also
* 3 References
* 4 External links
## Classification[edit]
The keratodermas are classified into the following subgroups:[2]:506
### Congenital[edit]
* Simple keratodermas
* Diffuse palmoplantar keratodermas
* Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* mal de Meleda
* Focal palmoplantar keratoderma
* Striate palmoplantar keratoderma
* Punctate palmoplantar keratoderma
* Keratosis punctata palmaris et plantaris
* Spiny keratoderma
* Focal acral hyperkeratosis
* Complex keratodermas
* Diffuse palmoplantar keratoderma
* Erythrokeratodermia variabilis
* Palmoplantar keratoderma of Sybert
* Olmsted syndrome
* Naegeli–Franceschetti–Jadassohn syndrome
* Focal palmoplantar keratoderma
* Papillon–Lefèvre syndrome
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Camisa disease
* Ectodermal dysplasias
* Clouston's hidrotic ectodermal dysplasia
* Acrokeratotic poikiloderma
* Dermatopathic pigmentosa reticularis
* Syndromic keratodermas
* Vohwinkel syndrome
* Palmoplantar keratoderma associated with esophageal cancer
* Palmoplantar keratoderma and spastic paraplegia
* Naxos disease
* Striate palmoplantar keratoderma, woolly hair, and left ventricular dilated cardiomyopathy
* Keratitis-ichthyosis-deafness syndrome
* Corneodermatosseous syndrome
* Huriez syndrome
* Oculocutaneous tyrosinemia
* Cardiofaciocutaneous syndrome
* Schöpf–Schulz–Passarge syndrome
### Acquired[edit]
* Acquired keratodermas
* AIDS-associated keratoderma
* Arsenical keratoses
* Calluses
* Climacteric keratoderma
* Clavi (Corns)
* Eczema
* Human papillomavirus
* Keratoderma blenorrhagicum
* Lichen planus
* Norwegian scabies
* Paraneoplastic keratoderma
* Psoriasis
* Reactive arthritis
* Secondary syphilis
* Tinea pedis
* Sézary syndrome
* Tuberculosis verrucosa cutis
* Drug-induced keratoderma[3]
## See also[edit]
* Palmoplantar keratoderma
* Skin lesion
* List of cutaneous conditions
* List of conditions caused by problems with junctional proteins
## References[edit]
1. ^ WordNet Search - 3.0[permanent dead link]
2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 778. ISBN 978-1-4160-2999-1.
## External links[edit]
Classification
D
* ICD-10: L85.1, L86, Q82.8
* SNOMED CT: 707209001
* v
* t
* e
Cutaneous keratosis, ulcer, atrophy, and necrobiosis
Epidermal thickening
* keratoderma: Keratoderma climactericum
* Paraneoplastic keratoderma
* Acrokeratosis paraneoplastica of Bazex
* Aquagenic keratoderma
* Drug-induced keratoderma
* psoriasis
* Keratoderma blennorrhagicum
* keratosis: Seborrheic keratosis
* Clonal seborrheic keratosis
* Common seborrheic keratosis
* Irritated seborrheic keratosis
* Seborrheic keratosis with squamous atypia
* Reticulated seborrheic keratosis
* Dermatosis papulosa nigra
* Keratosis punctata of the palmar creases
* other hyperkeratosis: Acanthosis nigricans
* Confluent and reticulated papillomatosis
* Callus
* Ichthyosis acquisita
* Arsenical keratosis
* Chronic scar keratosis
* Hyperkeratosis lenticularis perstans
* Hydrocarbon keratosis
* Hyperkeratosis of the nipple and areola
* Inverted follicular keratosis
* Lichenoid keratosis
* Multiple minute digitate hyperkeratosis
* PUVA keratosis
* Reactional keratosis
* Stucco keratosis
* Thermal keratosis
* Viral keratosis
* Warty dyskeratoma
* Waxy keratosis of childhood
* other hypertrophy: Keloid
* Hypertrophic scar
* Cutis verticis gyrata
Necrobiosis/granuloma
Necrobiotic/palisading
* Granuloma annulare
* Perforating
* Generalized
* Subcutaneous
* Granuloma annulare in HIV disease
* Localized granuloma annulare
* Patch-type granuloma annulare
* Necrobiosis lipoidica
* Annular elastolytic giant-cell granuloma
* Granuloma multiforme
* Necrobiotic xanthogranuloma
* Palisaded neutrophilic and granulomatous dermatitis
* Rheumatoid nodulosis
* Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction
Foreign body granuloma
* Beryllium granuloma
* Mercury granuloma
* Silica granuloma
* Silicone granuloma
* Zirconium granuloma
* Soot tattoo
* Tattoo
* Carbon stain
Other/ungrouped
* eosinophilic dermatosis
* Granuloma faciale
Dermis/
localized CTD
Cutaneous lupus
erythematosus
* chronic: Discoid
* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
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
|
Keratoderma
|
c0022579
| 8,224 |
wikipedia
|
https://en.wikipedia.org/wiki/Keratoderma
| 2021-01-18T18:47:09 |
{"umls": ["C0022579"], "wikidata": ["Q1739195"]}
|
A rare neural tube defect characterized by cystic dilatation of the central canal of the spinal cord, herniating posteriorly through a dorsal spinal defect. The malformation can occur anywhere along the spinal cord but appears to be more frequent in the posterior cervical and the lumbosacral region. It may be an isolated anomaly or be associated with other defects, including anorectal and genitourinary anomalies, or sacral agenesis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Myelocystocele
|
c4551677
| 8,225 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268813
| 2021-01-23T17:00:16 |
{"icd-10": ["Q05.0", "Q05.1", "Q05.2", "Q05.3", "Q05.4", "Q05.5", "Q05.6", "Q05.7", "Q05.8", "Q05.9"]}
|
Anemia of prematurity
SpecialtyPediatrics
Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants[1] with decreased hematocrit.[2] AOP is a normochronic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood cell growth factor.[3]
## Contents
* 1 Pathophysiology
* 2 Treatment
* 2.1 Transfusion
* 2.2 EPO
* 2.3 Transfusion management
* 3 See also
* 4 References
* 5 External links
## Pathophysiology[edit]
Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life.[4] Although their anemia is multifactorial, repeated blood sampling and reduced erythropoiesis with extremely low serum levels of erythropoietin (EPO) are major causative factors.[5][6][7] Blood sampling done for laboratory testing can easily remove enough blood to produce anemia.[4] Obladen, Sachsenweger and Stahnke (1987) studied 60 very low birth weight infants during the first 28 days of life. Infants were divided into 3 groups, group 1 (no ventilator support, 24 ml/kg blood loss), group 2(minor ventilated support, 60 ml/kg blood loss), and group 3(ventilated support for respiratory distress syndrome, 67 ml/kg blood loss). Infants were checked for clinical symptoms and laboratory signs of anemia 24 hours before and after the blood transfusion. The study found that groups 2 and 3 who had significant amount of blood loss, showed poor weight gain, pallor and distended abdomen. These reactions are the most frequent symptoms of anemia in very low birth weight infants.[8]
During the first weeks of life, all infants experience a decline in circulating red blood cell (RBC) volume generally expressed as blood hemoglobin concentration (Hb).[9] As anemia develops, there is even more of a significant reduction in the concentration of hemoglobin.[10] Normally this stimulates a significant increased production of erythropoietin (EPO), but this response is diminished in premature infants. Dear, Gill, Newell, Richards and Schwarz (2005) conducted a study to show that there is a weak negative correlation between EPO and Hb. The researchers recruited 39 preterm infants from 10 days of age or as soon as they could manage without respiratory support. They estimated total EPO and Hb weekly and 2 days after a blood transfusion. The study found that when Hb>10, EPO mean was 20.6 and when Hb≤10, EPO mean was 26.8. As Hb goes down, EPO goes up.[11] While the reason for this decreased response is not fully understood, Strauss (n.d.) states that it results from both physiological factors (e.g., the rapid rate of growth and need for a commensurate increase in RBC mass to accompany the increase in blood volume) and, in sick premature infants, from phlebotomy blood losses. In premature infants this decline occurs earlier and more pronounced that it does in healthy term infants. Healthy term infants Hb rarely falls below 9 g/dL at an age of approximately 10–12 weeks, while in premature infants, even in those without complicating illnesses, the mean Hb falls to approximately 8g/dL in infants of 1.0-1.5 kg birth weight and to 7g/dL in infants <1.0 kg. Because this postnatal drop in hemoglobin level is universal and is well tolerated in term infants, it is commonly referred to as the “physiologic” anemia of infancy. However, in premature infants the decline in Hb may be associated with abnormal clinical signs severe enough to prompt transfusions.[citation needed]
## Treatment[edit]
### Transfusion[edit]
AOP is usually treated by blood transfusion but the indications for this are still unclear. Blood transfusions have both infectious and non-infectious risks associated with them. Also, blood transfusions are costly and may add to parental anxiety. The best treatment for AOP is prevention of worsening of anemia by minimizing the amount of blood drawn from the infant (ie, anemia from phlebotomy). It is found that since blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, it would be useful to quantify blood loss attributable to phlebotomy overdraw (ie, blood collected in excess than what is strictly required for the requested lab tests). Lin and colleagues performed a study to see when and if phlebotomy overdraw was actually a significant problem.[4] They recorded all of the data that could be of influence such as the test performed, the blood collection container used, the infants location (neonatal intensive care unit (NICU) and intermediate intensive care unit), the infant’s weight sampling and the phlebotomist’s level of experience, work shift, and clinical role. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood. They found that the mean volume of blood drawn for the 578 tests exceeded that requested by the hospital laboratory by 19.0% ± 1.8% per test. The main factors of overdraw was: collection in blood containers without fill-lines, lighter weight infants and critically ill infants being cared for in the NICU.[4]
### EPO[edit]
Recombinant EPO (r-EPO) may be given to premature infants to stimulate red blood cell production. Brown and Keith studied two groups of 40 very low birth weight (VLBW) infants to compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same dose.[12] They established that more frequent dosing of the same weekly amount of r-EPO generated a significant and continuous increase in Hb in VLBW infants. The infants that received five dosages had higher absolute reticulocyte counts (219,857 mm³) than those infants that received only two dosages (173,361 mm³). However, it was noted that the response to r-EPO typically takes up to two weeks. This study also showed responses between two dosage schedules (two times a week and five times a week). Infants were recruited for gestational age—age since conception—≤27 weeks and 28 to 30 weeks and then randomized into the two groups, each totaling 500 U/kg a week. Brown and Keith found that after two weeks of r-EPO administration, Hb counts had increased and leveled off; the infants who received r-EPO five times a week had significantly higher Hb counts. This was present at four weeks for all infants ≤30 weeks gestation and at 8 weeks for infants ≤27 weeks gestation.[12]
To date, studies of r-EPO use in premature infants have had mixed results. Ohls et al. examined the use of early r-EPO plus iron and found no short-term benefits in two groups of infants (172 infants less than 1000 g and 118 infants 1000–1250 g). All r-EPO treated infants received 400 U/g three times a week until they reached 35 weeks gestational age. The use of r-EPO did not decrease the average number of transfusions in the infants born at less than 1000 g, or the percentage of infants in the 1000 to 1250 group. A multi-center European trial studied early versus late r-EPO in 219 infants with birth weights between 500 and 999 g. An r-EPO close of 750 U/kg/week was given to infants in both the early (1–9 weeks) and late (4–10 weeks) groups. The two r-EPO groups were compared to a control group who did not receive r-EPO. Infants in all three groups received 3 to 9 mg/kg of enteral iron. These investigators reported a slight decrease in transfusion and donor exposures in the early r-EPO group (1–9 weeks): 13% early, 11% late and 4% control group.[13] It is likely that only a carefully selected subpopulation of infants may benefit from its use. Contrary to what just said, Bain and Blackburn (2004) also state in another study the use of r-EPO does not appear to have a significant effect on reducing the numbers of early transfusions in most infants, but may be useful to reduce numbers of late transfusion in extremely low-birth-weight infants.[14] A British task force to establish transfusion guidelines for neonates and young children and to help try to explain this confusion recently concluded that “the optimal dose, timing, and nutritional support required during EPO treatment has yet to be defined and currently the routine use of EPO in this patient population is not recommended as similar reduction in blood use can probably be achieved with appropriate transfusion protocols.”[15]
### Transfusion management[edit]
Other strategies involve the reduction of blood loss during phlebotomy.[16][17]
For extremely low birth weight infants, laboratory blood testing using bedside devices offers a unique opportunity to reduce blood transfusions.[4] This practice has been referred to as point-of-care testing or POC. Use of POC tests to measure the most commonly ordered blood tests could significantly decrease phlebotomy loss and lead to a reduction in the need for blood transfusions among critically ill premature neonates as these tests frequently require much less volume of blood to be collected from the patient. A study was done by Madan and colleagues to test this theory by conducting a retrospective chart review on all inborn infants <1000g admitted to the NICU that survived for 2 weeks of age during two separate 1 year time periods.[18] Conventional bench top laboratory analysis during the first year was done using Radiometer Blood Gas and Electrolyte Analyzer. Bedside blood gas analysis during the second year was performed using a point-of-care analyzer (iSTAT). An estimated blood loss in the two groups was determined based on the number of specific blood tests on individual infants. The study found that there was an estimated 30% reduction in the total volume of blood removed for the blood tests. This study concluded that there is modern technology that can be used to limit the amount of blood removed from these infants thereby reducing the need for blood product transfusions (or the number of transfusions) and r-EPO.[18]
## See also[edit]
* List of circulatory system conditions
* List of hematologic conditions
## References[edit]
1. ^ Widness JA (November 2008). "Pathophysiology of Anemia During the Neonatal Period, Including Anemia of Prematurity". NeoReviews. 9 (11): e520–e525. doi:10.1542/neo.9-11-e520. PMC 2867612. PMID 20463861.
2. ^ "Anemia of prematurity". Retrieved 2010-05-31.
3. ^ Bishara, Nader (February 2009). "Current controversies in the management of anemia of prematurity". Seminars in Perinatology. 33 (1): 29–34. doi:10.1053/j.semperi.2008.10.006. PMID 19167579.
4. ^ a b c d e Lin, James C.; Strauss, Ronald G.; Kulhavy, Jeff C.; Johnson, Karen J.; Zimmerman, M. Bridget; Cress, Gretchen A.; Connolly, Natalie W.; Widness, John A. (2000-08-01). "Phlebotomy Overdraw in the Neonatal Intensive Care Nursery". Pediatrics. 106 (2): e19. doi:10.1542/peds.106.2.e19. ISSN 0031-4005. PMID 10920175.
5. ^ Adams, M., Benitz, W., Geaghan, S., Kumar, R., Madan, A., & Widness, J. (2005). Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants. Journal of Perinatology 25, 21-25. Retrieved November 16, 2007, from EbscoHost Research Databases.
6. ^ Astruc, D., Donato, L., Haddad, J., Matis, J., & Messer, J. (1993). Early treatment of premature infants with recombinant human erythropoietin. Pediatrics 92(4), 519-523. Retrieved December 9, 2007, from EbscoHost Research Databases
7. ^ Connolly, N., Cress, G., Johnson, K., Kulhavy, J., Lin, J., Strauss, R., Widness, J., & Zimmerman, M. (2000). Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics 106(2), 19. Retrieved November 16, 2007, from EbscoHost Research Databases.
8. ^ Obladen, M., Sachsenweger, M., & Stahnke, M. (1988). Blood sampling in very low birth weight infants receiving different levels of intensive care. Abstract retrieved November 27, 2007, from EbscoHost Research Databases.
9. ^ Strauss, R. (n.d.). Neonatal anemia: Pathophysiology and treatment. Transfusion Immunology and Medicine, 341-343. Retrieved December 10, 2007, from Google Scholar Research Databases.
10. ^ Boxwell G. (2000). Chapter 8 hematological problems: Anemia. Neonatal Intensive Care Nursing, 164-187. Retrieved December 12, 2007, from EbscoHost Research Databases.
11. ^ Dear, F., Gill, G., Newell, J., Richards, M., & Schwarz B. (2005). Effects of transfusion in anemia of prematurity. Pediatric Hematology and Oncology 22, 551-559. Retrieved December 9, 2007, from EbscoHost Research Databases.
12. ^ a b Brown, Mark S.; Keith, Julian F. (1999-08-01). "Comparison Between Two and Five Doses a Week of Recombinant Human Erythropoietin for Anemia of Prematurity: A Randomized Trial". Pediatrics. 104 (2): 210–215. doi:10.1542/peds.104.2.210. ISSN 0031-4005. PMID 10428996. S2CID 24961879.
13. ^ Bain, A., & Blackburn, S. (2004). Issues in transfusing preterm infants in the NICU. Journal of Perinatal and Neonatal Nursing 18(2), 170-182. Retrieved December 4, 2007, from EbscoHost Research Databases.
14. ^ Bain, Annamarie; Blackburn, Susan (April 2004). "Issues in Transfusing Preterm Infants in the NICU". The Journal of Perinatal & Neonatal Nursing. 18 (2): 170–182. doi:10.1097/00005237-200404000-00011. ISSN 0893-2190. PMID 15214254. S2CID 21928067.
15. ^ New, H. V.; Stanworth, S. J.; Engelfriet, C. P.; Reesink, H. W.; McQuilten, Z. K.; Savoia, H. F.; Wood, E. M.; Olyntho, S.; Trigo, F. (2009). "Neonatal transfusions". Vox Sanguinis. 96 (1): 62–85. doi:10.1111/j.1423-0410.2008.01105.x. ISSN 1423-0410. PMID 19121200.
16. ^ Bishara N, Ohls RK (February 2009). "Current controversies in the management of the anemia of prematurity". Semin. Perinatol. 33 (1): 29–34. doi:10.1053/j.semperi.2008.10.006. PMID 19167579.
17. ^ Lopriore, Enrico (July 2019). "Updates in red blood cell and platelet transfusions in neonates". Am J Perinatol. 36 (suppl S2): S37–S40 – via PubMed.
18. ^ a b Madan, Ashima; Kumar, Rahi; Adams, Marian M; Benitz, William E; Geaghan, Sharon M; Widness, John A (2004-10-07). "Reduction in Red Blood Cell Transfusions Using a Bedside Analyzer in Extremely Low Birth Weight Infants". Journal of Perinatology. 25 (1): 21–25. doi:10.1038/sj.jp.7211201. ISSN 0743-8346. PMID 15496875.
## External links[edit]
Classification
D
* ICD-10: P61.2
* ICD-9-CM: 776.6
External resources
* eMedicine: article/978238
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Anemia of prematurity
|
c0158996
| 8,226 |
wikipedia
|
https://en.wikipedia.org/wiki/Anemia_of_prematurity
| 2021-01-18T19:01:22 |
{"umls": ["C0158996"], "wikidata": ["Q4761649"]}
|
16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.
People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. In 16p11.2 deletion syndrome, expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Some people with this disorder have recurrent seizures (epilepsy).
Some affected individuals have minor physical abnormalities such as low-set ears or partially webbed toes (partial syndactyly). People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities.
## Frequency
Most people tested for the 16p11.2 deletion have come to medical attention as a result of developmental delay or autistic behaviors. Other individuals with the 16p11.2 deletion have no associated health or behavioral problems, and so the deletion may never be detected. For this reason, the prevalence of this deletion in the general population is difficult to determine but has been estimated at approximately 3 in 10,000.
## Causes
People with 16p11.2 deletion syndrome are missing a sequence of about 600,000 DNA building blocks (base pairs), also written as 600 kilobases (kb), at position p11.2 on chromosome 16. This deletion affects one of the two copies of chromosome 16 in each cell. The 600 kb region contains more than 25 genes, and in many cases little is known about their function. Researchers are working to determine how the missing genes contribute to the features of 16p11.2 deletion syndrome.
### Learn more about the chromosome associated with 16p11.2 deletion syndrome
* chromosome 16
## Inheritance Pattern
16p11.2 deletion syndrome is considered to have an autosomal dominant inheritance pattern because a deletion in one copy of chromosome 16 in each cell is sufficient to cause the condition. However, most cases of 16p11.2 deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, although they can pass the condition to their children. Several examples of inherited 16p11.2 deletion have been reported. In inherited cases, other family members may be affected as well.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
16p11.2 deletion syndrome
|
c3150154
| 8,227 |
medlineplus
|
https://medlineplus.gov/genetics/condition/16p112-deletion-syndrome/
| 2021-01-27T08:25:48 |
{"gard": ["10740"], "omim": ["611913"], "synonyms": []}
|
Ulcerative dermatitis
SpecialtyDermatology
Ulcerative dermatitis is a skin disorder in rodents associated with bacterial growth often initiated by self-trauma due to a possible allergic response. Although other organisms can be involved, bacteria culture frequently shows Staphylococcus aureus. Primarily found on the rib cage, neck, and shoulder, lesions are often irregular, circumscribed, and moist. Intense itching may lead to scratching which may aggravate and perpetuate the lesion. Destruction of the epidermis along with underlying pustules or abscesses, and granulomatous inflammation, may be present.[1]
In cases where topical treatment alone does not resolve the dermatitis and irritants are not known, a secondary bacterial, fungal or yeast infection might be present and may require an anti-fungal or antibiotics to be prescribed by the veterinarian to affect a cure.[1]
In rats, this skin disorder may be observed on the neck and head, often secondary to skin trauma from scratches or fighting.[2]
## See also[edit]
* List of skin diseases
* Skin lesion
* Skin ulcer
## References[edit]
1. ^ a b "Dermatitis/Eczema". Rat Health Guide. June 29, 2003. Retrieved 2009-01-26.
2. ^ "Merck Veterinary Manual - Skin Diseases". Retrieved 2009-01-26.
* v
* t
* e
Dermatitis and eczema
Atopic dermatitis
* Besnier's prurigo
Seborrheic dermatitis
* Pityriasis simplex capillitii
* Cradle cap
Contact dermatitis
(allergic, irritant)
* plants: Urushiol-induced contact dermatitis
* African blackwood dermatitis
* Tulip fingers
* other: Abietic acid dermatitis
* Diaper rash
* Airbag dermatitis
* Baboon syndrome
* Contact stomatitis
* Protein contact dermatitis
Eczema
* Autoimmune estrogen dermatitis
* Autoimmune progesterone dermatitis
* Breast eczema
* Ear eczema
* Eyelid dermatitis
* Topical steroid addiction
* Hand eczema
* Chronic vesiculobullous hand eczema
* Hyperkeratotic hand dermatitis
* Autosensitization dermatitis/Id reaction
* Candidid
* Dermatophytid
* Molluscum dermatitis
* Circumostomy eczema
* Dyshidrosis
* Juvenile plantar dermatosis
* Nummular eczema
* Nutritional deficiency eczema
* Sulzberger–Garbe syndrome
* Xerotic eczema
Pruritus/Itch/
Prurigo
* Lichen simplex chronicus/Prurigo nodularis
* by location: Pruritus ani
* Pruritus scroti
* Pruritus vulvae
* Scalp pruritus
* Drug-induced pruritus
* Hydroxyethyl starch-induced pruritus
* Senile pruritus
* Aquagenic pruritus
* Aquadynia
* Adult blaschkitis
* due to liver disease
* Biliary pruritus
* Cholestatic pruritus
* Prion pruritus
* Prurigo pigmentosa
* Prurigo simplex
* Puncta pruritica
* Uremic pruritus
Other
* substances taken internally: Bromoderma
* Fixed drug reaction
* Nummular dermatitis
* Pityriasis alba
* Papuloerythroderma of Ofuji
* v
* t
* e
Inflammation
Symptoms
* Flushing (Rubor)
* Fever (Calor)
* Swelling (Tumor)
* Pain (Dolor)
* Malaise
Mechanism
Acute
Plasma-derived mediators
* Bradykinin
* complement
* C3
* C5a
* MAC
* coagulation
* Factor XII
* Plasmin
* Thrombin
Cell-derived mediators
preformed:
* Lysosome granules
* biogenic amines
* Histamine
* Serotonin
synthesized on demand:
* cytokines
* IFN-γ
* IL-8
* TNF-α
* IL-1
* eicosanoids
* Leukotriene B4
* Prostaglandins
* Nitric oxide
* Kinins
Chronic
* Macrophage
* Epithelioid cell
* Giant cell
* Granuloma
Other
* Acute-phase reaction
* Vasodilation
* Increased vascular permeability
* Exudate
* Leukocyte extravasation
* Chemotaxis
Tests
* Full blood count
* Leukocytosis
* C-reactive protein
* Erythrocyte sedimentation rate
General
* Lymphadenopathy
* List of inflammed body part states
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ulcerative dermatitis
|
c3687015
| 8,228 |
wikipedia
|
https://en.wikipedia.org/wiki/Ulcerative_dermatitis
| 2021-01-18T19:01:50 |
{"wikidata": ["Q7878801"]}
|
A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-18 (BDPLT18) is caused by homozygous mutation in the RASGRP2 gene (605577) on chromosome 11q13. One such family has been reported.
Clinical Features
Canault et al. (2014) reported 3 sibs, born of consanguineous parents, with a bleeding disorder due to defective platelet function. The patients developed mucocutaneous bleeding around 18 months of age. Features included epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. Bleeding times were increased, and patient platelets showed reduced aggregation in response to ADP or epinephrine.
Inheritance
The transmission pattern of BDPLT18 in the family reported by Canault et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 3 sibs, born of consanguineous parents, with a platelet-type bleeding disorder, Canault et al. (2014) identified a homozygous mutation in the RASGRP2 gene (G248W; 605577.0001). The mutation was found by exome sequencing and segregated with the disorder in the family. In vitro functional studies indicated that the mutation caused defective RASGRP2 function, resulting in defective platelet inside-out and outside-in signaling and interfering with platelet aggregation and spreading. The functional deficiencies were confined to platelets and megakaryocytes with no alterations in leukocytes. Platelets from heterozygous carriers showed impaired platelet adhesion under flow conditions in the absence of clinical bleeding, suggesting that partial inhibition of the RASGRP2 catalytic domain could be a therapeutic target to prevent thrombosis.
INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Epistaxis HEMATOLOGY \- Mucocutaneous bleeding due to platelet dysfunction \- Impaired platelet aggregation and spreading LABORATORY ABNORMALITIES \- Prolonged bleeding time MISCELLANEOUS \- One family has been reported (last curated July 2014) \- Onset in infancy MOLECULAR BASIS \- Caused by mutation in the RAS guanyl nucleotide-releasing protein 2 gene (RASGRP2, 605577.0001 ) ▲ 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
|
BLEEDING DISORDER, PLATELET-TYPE, 18
|
c4014584
| 8,229 |
omim
|
https://www.omim.org/entry/615888
| 2019-09-22T15:50:43 |
{"doid": ["0111051"], "omim": ["615888"], "orphanet": ["420566"], "synonyms": ["Bleeding disorder due to calcium- and DAG-regulated guanine exchange factor-1 deficiency"]}
|
17q23.1-q23.2 microduplication is a newly described cause of familial isolated clubfoot.
## Epidemiology
It has been described in three families.
## Clinical description
All cases with clubfoot were male and clubfoot was bilateral in all except one case. Clinically, the feet were short, with broad and overlapping toes. Mild nail hypoplasia was present in two affected individuals and mild short stature was common.
## Genetic counseling
The microduplication segregated with autosomal-dominant clubfoot in all three families but with incomplete penetrance. This microduplication was identified by array CGH (comparative genomic hybridization).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Familial clubfoot due to 17q23.1q23.2 microduplication
|
c3150880
| 8,230 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238578
| 2021-01-23T18:59:33 |
{"omim": ["613618"], "icd-10": ["Q66.8"], "synonyms": ["Hereditary clubfoot due to 17q23.1-q23.2 microduplication"]}
|
Radioulnar synostosis
Other namesRadioulnar fusion
Congenital radioulnar synostosis in a 7 year old boy
SpecialtyOrthopaedics
Radioulnar synostosis is a rare condition where there is an abnormal connection between the radius and ulna bones of the forearm.[1] This can be present at birth (congenital), when it is a result of a failure of the bones to form separately, or following an injury (post-traumatic).[2]
It typically causes restricted movement of the forearm, in particular rotation (pronation and supination), though is not usually painful unless it causes subluxation of the radial head.[1] It can be associated with dislocation of the radial head which leads to limited elbow extension.[2]
## Contents
* 1 Types
* 1.1 Congenital
* 1.2 Acquired
* 2 Treatment
* 3 References
* 4 External links
## Types[edit]
### Congenital[edit]
Congenital radioulnar synostosis is rare, with approximately 350 cases reported in journals, and it typically affects both sides (bilateral) and can be associated with other skeletal problems such as hip and knee abnormalities, finger abnormalities (syndactyly or clinodactyly), or Madelung's deformity.[1] It is sometimes part of known genetic syndromes such as Klinefelter syndrome (48,XXXY variant), Apert, Williams, Cornelia de Lange, or Holt-Oram.[1][3] It has been reported to run in families typically following an autosomal dominant inheritance pattern which means children of an affected parent have a 50% chance of having the condition.[3] When associated with amegakaryocytic thrombocytopenia this inheritance has been found to be caused by mutations to the HOXA11 gene.[4]
### Acquired[edit]
Post-traumatic cases are most likely to develop following surgery for a forearm fracture, this is more common with high-energy injuries where the bones are broken into many pieces (comminuted).[1] It can also develop following soft tissue injury to the forearm where there is haematoma formation.[citation needed]
## Treatment[edit]
It is sometimes possible to correct the problem with surgery, though this has high failure rates for treatment of post-traumatic radioulnar synostosis. [1] Indication for the surgical treatment of congenital radioulnar synostosis include severe disability due to bilateral disorder or hyperpronation ≥90 [1]
## References[edit]
1. ^ a b c d e f Wurapa, Raymond (7 January 2017). "Radioulnar Synostosis: Background, Pathophysiology, Etiology". eMedicine. Retrieved 2 March 2017.
2. ^ a b "Congenital radio-ulnar synostosis | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2 March 2017.
3. ^ a b "OMIM Entry - RADIOULNAR SYNOSTOSIS". omim.org. Retrieved 2 March 2017.
4. ^ "OMIM Entry - RADIOULNAR SYNOSTOSIS WITH AMEGAKARYOCYTIC THROMBOCYTOPENIA 1; RUSAT1". omim.org. Retrieved 2 March 2017.
## External links[edit]
* Radioulnar synostosis at eMedicine
Classification
D
* ICD-10: Q74.0
* ICD-9-CM: 755.53
* OMIM: 179300
* MeSH: C562408 C562408, C562408
External resources
* Orphanet: 3269
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Radioulnar synostosis
|
c0431795
| 8,231 |
wikipedia
|
https://en.wikipedia.org/wiki/Radioulnar_synostosis
| 2021-01-18T18:37:12 |
{"gard": ["10876"], "mesh": ["C562408"], "umls": ["C0431795"], "orphanet": ["3269"], "wikidata": ["Q16892594"]}
|
A number sign (#) is used with this entry because autosomal dominant spastic paraplegia-3A (SPG3A) is caused by heterozygous mutation in the ATL1 gene (606439) on chromosome 14q22.
See also autosomal dominant hereditary sensory neuropathy type 1D (HSN1D; 613708), an allelic disorder with a different phenotype.
Description
The hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997).
SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see 270800), and X-linked (see 303350)) and whether progressive spasticity occurs in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. The major neuropathologic feature of autosomal dominant, uncomplicated SPG is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Spinocerebellar fibers are involved to a lesser extent. Since the description of 'pure' hereditary spastic paraparesis of late onset by Strumpell (1904), many 'complicated' forms of the disorder have been reported and the question as to whether a 'pure' form exists has been raised off and on. Probably in large part because of their exceptional length, the pyramidal tracts are unusually vulnerable to both acquired and genetic derangement. Although a majority of reported families have displayed recessive inheritance, 10 to 30% of families have a dominant pattern and in fact recessive inheritance of a 'pure' spastic paraplegia may be rare.
### Genetic Heterogeneity of Autosomal Dominant Spastic Paraplegia
In addition to SPG3A, other forms of autosomal dominant spastic paraplegia for which the molecular basis is known include SPG4 (182601), caused by mutation in the SPAST gene (604277) on 2p22; SPG6 (600363), caused by mutation in the NIPA1 gene (608145) on 15q11; SPG8 (603563), caused by mutation in the KIAA0196 gene (610657) on 8q24; SPG9A (601162), caused by mutation in the ALDH18A1 gene (138250) on 10q24; SPG10 (604187), caused by mutation in the KIF5A gene (602821) on 12q13; SPG12 (604805), caused by mutation in the RTN2 gene (603183) on 19q13; SPG13 (605280), caused by mutation in the SSPD1 gene (118190) on 2q33.1; SPG31 (610250), caused by mutation in the REEP1 gene (609139) on 2p11; SPG33 (610244), caused by mutation in the ZFYVE27 gene (610243) on 10q24; SPG72 (615625), caused by mutation in the REEP2 gene (609347) on 5q31; SPG73 (616282), caused by mutation in the CPT1C gene (608846) on 19q13; and SPG80 (618418), caused by mutation in the UBAP1 gene (609787) on chromosome 9p13.
Autosomal dominant spastic paraplegia has been mapped to chromosomes 9q (SPG19; 607152), 1p31-p21 (SPG29; 609727), 12q23-q24 (SPG36; 613096), 8p21.1-q13.3 (SPG37; 611945), 4p16-p15 (SPG38; 612335), and 11p14.1-p11.2 (SPG41; 613364).
Clinical Features
In the Amish of Lancaster County, Pa., a kindred with spastic paraplegia in 3 generations was observed (McKusick, 1965). In this closed community the origin of the de novo mutation could be identified with considerable certainty. The disease was early in onset but very slowly progressive or even static. This same type of congenital stationary familial paraplegia was described in 7 members of 2 generations by Hohmann (1957). In contrast to the early-onset, static form of disease in the Amish family, Thurmon and Walker (1971) reported a family from Deer Isle, Maine, in which many affected members had onset in the second or third decade with steady progression of neurologic defect.
Schwarz and Liu (1956) reported several families including one originally reported by Bayley (1897) which in 1956 contained 22 affected persons in 6 generations. Aagenaes (1959) described a family with 31 cases in 4 generations. Prognosis for life was good. Histopathologic changes were found bilaterally in the lateral corticospinal tracts in the thoracic cord and in the fasciculus gracilis. The confusion of the spinocerebellar degenerations is illustrated by the fact that some members of Aagenaes' family had ataxia in addition to spastic paraplegia. Behan and Maia (1974) studied 6 families. In 2 cases autopsy studies were performed. The authors concluded that distal axonal degeneration of the long ascending and descending tracts in the spinal cord is characteristic. McLeod et al. (1977) found no abnormality of motor and sensory nerve conduction in 10 persons in 3 families. In one family 4 generations were affected, in a second, 3 generations, and in a third 2 brothers were affected, possibly with the X-linked form. Sack et al. (1978) described affected members of 6 generations of a kindred. Onset was in the fourth decade or later, with symptoms of progressive gait difficulties, lower limb spasticity, and weakness. No sensory cerebellar and cranial nerve changes were associated. Anatomic changes in 1 affected person studied at autopsy were confined to the lateral corticospinal tracts and the fasciculus gracilis. Opjordsmoen and Nyberg-Hansen (1980) described a family from northern Norway with spastic paraplegia and type III syndactyly (fusion of fingers 4 and 5). The two traits were transmitted together through 3 generations and 9 affected persons. The spastic paraplegia was of unusual type: neurogenic bladder was the earliest manifestation. Indeed, the spastic paraplegia easily escaped attention. Are these two genes linked? Harding (1981) reviewed 22 families with 'pure' spastic paraplegia and found autosomal dominant inheritance in 19 and autosomal recessive in 3. She identified 2 forms on the basis of age of onset: type I with onset mainly before age 35 years; type II with onset usually after age 35 years.
Cooley et al. (1990) identified 71 affected individuals in 7 generations of a New England family; of these they examined 17 cases. Onset occurred at or before 3 years of age with involvement limited to the lower limbs. They suggested that although in the first year of life the physical examination is normal, in the second year long tract signs are evident on examination and there is a rapid increase in spasticity followed by a delay in walking. Crutches are occasionally necessary in the teens and often necessary after the age of 18. No progression of spasticity was observed after age 7. Cooley et al. (1990) reviewed the medical records of 25 family members and examined 16 of them. They felt that children free of signs by age 3 years could be assumed to be unaffected. They further suggested that early, aggressive, habilitative intervention may result in more functional ambulation for the youngest family members. No significant progression was observed after 3 years of age.
Scheltens et al. (1990) described a Dutch family with 15 affected members in 3 generations. Onset of clinical signs was in the fourth or fifth decade. The disease was mild; only a few of the affected persons became chairbound late in life. Mild sphincter disturbances were noted in 6 patients. There were no sensory changes.
Polo et al. (1993) described the genetic and clinical features of 46 patients in 9 families. Inheritance was autosomal dominant in 7, but was thought to be autosomal recessive in 2. The evidence for recessive inheritance was the occurrence in males and females in one generation with consanguineous parents (see 270800). Among the dominant kindreds, 5 corresponded to type I with onset before 35 years and 2 to type II with onset over 35 years. Irrespective of genetic type, serial evaluation demonstrated that the main symptom was slowly progressive spastic gait, extremely variable in severity, associated in some patients with decreased vibratory sense and micturition disorders (generally as late features). Among dominant families, the disease tended to be more severe in late-onset cases. No patient had symptoms in the upper limbs and plantar responses were flexor in 6 symptomatic patients.
Durr et al. (1994) studied 23 families with pure autosomal dominant spastic paraplegia and found a unimodal distribution of age of onset. The clinical manifestations of early-onset and late-onset patients were not significantly different. There was no evidence of anticipation or imprinting. Spasticity, sphincter disturbance, decreased vibratory sense, and muscle weakness increased with disease duration. Except for 1 family with electrophysiologic evidence of an axonal neuropathy, there were no clinical features by which the families could be distinguished.
Schady and Smith (1994) reported a large kindred transmitting typical 'pure' hereditary spastic paraplegia and found electrophysiologic evidence of a sensory polyneuropathy, with normal motor nerve conduction velocities. Sural nerve biopsies demonstrated severe loss of large diameter fibers and relative preservation of small myelinated and nonmyelinated fibers. Members of this family had previously been shown to have delayed central motor conduction (Schady et al., 1991). The mild sensory changes, the absence of mutilating ulcers, and the dominant mode of inheritance clearly distinguished the disorder in this family from autosomal recessive hereditary sensory neuropathy with spastic paraplegia (256840). Although the sensory changes were subclinical and therefore may have been missed in other cases of 'pure' hereditary spastic paraplegia, the authors speculated that HSP with abnormal sensory action potentials may be a distinct entity. In their own studies of 17 kinships with HSP (Schady et al., 1991; Schady and Sheard, 1990), they had found only 2 other patients with abnormal sensory action potentials.
Thurmon et al. (1999) restudied the large Deer Isle, Maine, family reported by Thurmon and Walker (1971). Analysis of age of onset was found to be consistent with anticipation in this family. The findings were considered consistent with an unstable trinucleotide repeat occurring primarily in the female germline. On reexamination they were impressed with variable spasticity and Babinski responses. Indeed, spasticity was said not to be a prominent aspect of the disorder; most affected relatives exhibited leg paralysis, with little or no spasticity. Only individuals with long duration of the disorder (more than 22 years) typically manifested a combination of paraplegic gait, hyperreflexia, and Babinski sign. One patient was thought to have been homozygous for the mutation. He was affected with spastic quadriplegia and mental retardation and died at the age of 11.5 years of pneumonia. The parents were consanguineous. The father was known to be affected at the time of report in 1971; since that time the boy's mother had become affected.
In a family with 6 members affected with an early-onset severe form of spastic paraplegia, Dalpozzo et al. (2003) identified a heterozygous mutation in the SPG3A gene (606439.0006). All affected members had onset in infancy with delayed motor milestones, gait impairment, spastic paraparesis, distal atrophy, and lower limb weakness. Because of the early onset, the first patients were misdiagnosed with cerebral palsy, and the index patient (mother of 5 affected members) was unaware that she had a genetically transmissible disease. Two patients had the unusual sign of mild hand atrophy.
Durr et al. (2004) identified mutations in the atlastin gene in 12 of 31 (39%) families in France with early-onset autosomal dominant SPG. Mean age at onset was 4.6 years (range, birth to 14 years). The overall clinical phenotype was of a pure spastic gait disorder. Scoliosis was present in 22% of patients, mild pes cavus in 15%, and brisk upper limb reflexes in 10%. Sensation was not impaired, and only 13% of patients reported decreased vibration sense in the ankles. Two patients had postural tremor in the upper limbs. One family showed incomplete penetrance.
Rainier et al. (2006) reported a mother and son with SPG3A confirmed by the finding of a mutation in the SPG3A gene (L157W; 606439.0008). Genetic analysis of family members indicated that the mutation occurred de novo in the mother. The mother was a 34-year-old woman with uncomplicated nonprogressive spastic paraplegia since infancy who was originally diagnosed with spastic diplegic cerebral palsy. She was correctly diagnosed with SPG after her son developed similar clinical symptoms at age 10 months. Both patients showed brisk lower limb reflexes, clonus, and spastic gait with normal bulbar and upper limb function, normal bowel and urinary control, and normal intelligence. Rainier et al. (2006) emphasized the importance of the correct diagnosis of SPG for genetic counseling because the recurrence risk may be as high as 50%.
Ivanova et al. (2007) identified SPG3A mutations in 12 (6.6%) of 182 European or Australian probands with spastic paraplegia. Mean age at onset in SPG3A probands was 3 years. In the 12 probands and 24 affected family members, age of onset was before 10 years of age, except in 1 family with mean onset of 14 years and notable variability (range, 8 to 28 years). In addition to typical features of SPG, 6 (17%) of 36 affected individuals had an axonal, predominantly motor peripheral polyneuropathy, confirmed by pathologic and electrophysiologic studies. The 6 patients with neuropathy originated from 5 unrelated families, and 4 of these patients had pes cavus.
### Clinical Variability
Orlacchio et al. (2011) reported a 3-generation Zulu family from South Africa with an unusual form of late-onset SPG3A. The 68-year-old proband presented with progressive walking difficulties at age 56, and required a walking aid since age 66. He had mild mental retardation (IQ of 62), urinary incontinence, and thin corpus callosum without cerebellar involvement or white matter abnormalities. Inheritance was clearly autosomal dominant. Other affected family members had a similar disease course, with late onset (range, 38-51 years), spasticity restricted to the lower limbs, mental impairment, and thin corpus callosum on brain imaging. Genomewide linkage analysis followed by direct sequencing identified a heterozygous mutation in exon 12 of the ATL1 gene in affected individuals (R416C; 606439.0013).
Inheritance
SPG3A is transmitted in an autosomal dominant pattern and may show incomplete penetrance (Durr et al., 2004).
Varga et al. (2013) reported 2 unrelated families with hereditary spastic paraplegia in which family pedigree analysis suggested different inheritance patterns, but whole-exome sequencing identified pathogenic mutations in the ATL1 gene, consistent with SPG3A. Four Moroccan sibs in the first family, in which there were several consanguineous marriages, showed onset of lower limb spasticity in the first decade. Two patients also had upper limb involvement. The pedigree pattern suggested autosomal recessive inheritance of the disorder, but whole-exome sequencing identified an ATL1 mutation (R415Q; 606439.0014): 3 sibs were homozygous and 1 was heterozygous for the mutation. The heterozygous R415Q mutation was then found in 3 unaffected family members and in 2 family members who had very subtle signs of the disorder (hyperreflexia). These findings suggested complete penetrance for the mutation in homozygous state and incomplete penetrance for the mutation in heterozygous state. The second family had previously been reported by Raggio et al. (1973) as showing X-linked transmission of a pure spastic paraplegia. Whole-exome sequencing of 1 of the affected males identified a heterozygous ATL1 mutation (R415W; 606439.0007). The mutation was then identified in 3 affected and 3 unaffected members of the family, consistent with incomplete penetrance. Two of the unaffected carriers were women, and family history indicated that most unaffected women were obligate carriers. These findings were consistent with sex-associated reduced penetrance of this mutation. Varga et al. (2013) also identified heterozygosity for the R415W mutation in 1 of 83 Spanish patients with apparent sporadic HSP and in 2 of 28 Russian patients with dominant HSP. Evidence again suggested incomplete penetrance in these families. Both mutations, c.1244A-G (R415Q) and c.1243C-T (R415W), occur at a CpG nucleotide (on the plus and minus strands, respectively) and thus may represent a mutation hotspot due to spontaneous deamination of methylated cytosines. R415 is a highly conserved residue that does not localize to a known protein domain. Varga et al. (2013) suggested that female ATL1 mutation carriers may be more protected from developing disease compared to male carriers.
### Possible Autosomal Recessive Inheritance
Khan et al. (2014) reported a consanguineous Pakistani family in which 6 males presented with pure SPG before 2 years of age. Clinical features included spastic gait, toe walking, hyperreflexia of the lower limbs, pes cavus, reduced vibration sense, peripheral numbness and tingling, urinary bladder hyperactivity, and scoliosis. Cognitive function was normal. Whole-exome sequencing identified a homozygous missense variant in the ATL1 gene (R118Q; 606439.0015) that was present in all affected family members. Seven family members were heterozygous for the variant, all of whom were asymptomatic except for 1 woman who had subclinically reduced vibration sensation. Functional studies of the variant were not performed. Khan et al. (2014) concluded that SPG3A in this family was transmitted in an autosomal recessive pattern, adding to the clinical complexity of the disorder.
Diagnosis
Schule et al. (2006) presented a 13-item scale designed to rate functional impairment in pure forms of spastic paraplegia. The scale measures items including walking distance, gait quality, maximum gait speed, spasticity, weakness, and pain. The scale can be performed in an outpatient setting, requires no special equipment, and was found to be a reliable and valid measure of disease severity.
Population Genetics
In a nationwide survey of Japanese patients, Hirayama et al. (1994) estimated the prevalence of all forms of spinocerebellar degeneration to be 4.53 per 100,000; of these, 3.9% were thought to have hereditary spastic paraplegia.
Mapping
Boustany et al. (1987) studied a family with 33 members affected with autosomal dominant 'pure' familial spastic paralysis. Linkage studies excluded close linkage to HLA, C8, PGM1, and P blood group. Positive lod scores were obtained with GC (139200) and Rh (111700). In 1 of 3 families, Hazan et al. (1993) found close linkage to a group of markers on 14q; maximum multipoint lod score = 10. On the other hand, the chromosome 14q candidate region was entirely excluded in the 2 other families, providing evidence of genetic heterogeneity within a clinically homogeneous form of familial spastic paraplegia.
Gispert et al. (1995) reported 3 large German pedigrees with autosomal dominant pure familial spastic paraplegia. One of the pedigrees demonstrated linkage to a 7-cM region on 14q, whereas the other 2 pedigrees were excluded from this region, confirming genetic heterogeneity of the disease.
Dube et al. (1997) undertook linkage analysis with 21 families with uncomplicated autosomal dominant hereditary spastic paraplegia, testing for linkage to the 3 known loci: SPG3 on 14q, SPG4 on 2p, and SPG4a on 15q. (The chromosome 15-linked form of hereditary spastic paraplegia, referred to as SPG4a by Dube et al. (1997), is referred to here as SPG6.) Linkage to SPG4 was found in 3 of the families and was excluded in several other families by multipoint linkage analysis. They developed a combined analytical approach which permitted conclusive linkage analysis on small-to-medium sized families, under the restrictions of genetic heterogeneity.
Among the 33 SPG kindreds reported by the hereditary spastic paraplegia working group (Fink et al., 1996), linkage to 2p was the most common, being observed in 15 kindreds (45%). Two kindreds (6%) were linked to 14q, and linkage to 15q was observed in 1 kindred (3%). Known SPG loci on these 3 chromosomes were excluded in 15 (45%) of 33 autosomal dominant SPG kindreds.
Huang et al. (1997) mapped autosomal dominant spastic paresis in a family in Northern Tibet to 14q11.2-q24.3 using microsatellite markers. Linkage to 2p24-p21 (SPG4) and 15q11.1 (SPG6), which have been found for other pedigrees with dominant spastic paresis, was excluded. In all affected individuals in the Tibetan family, signs of spastic paraplegia were confined to the legs. The younger individuals showed a positive Babinski. All managed to survive and provide adequately for their living, despite the extreme conditions in Northern Tibet, at an altitude of about 4,300 m.
### Heterogeneity
Subramony et al. (2009) reported a large 6-generation Caucasian American family in which 8 living individuals had adult-onset spastic paraplegia inherited in an autosomal dominant pattern. Linkage to 14 known autosomal dominant SPG loci was excluded. The phenotype was relatively homogeneous, with onset after age 35 years (except in 1 individual) of a pure spastic paraplegia mainly affecting the lower limbs and hyperreflexia of the upper limbs. Most individuals had loss of vibratory sense in the lower limbs, and 3 had urinary urgency. Two complained of mild recall deficits at age 77 and 80 years, respectively. There was also evidence of anticipation in later generations. Subramony et al. (2009) referred to the candidate locus as SPG40.
Molecular Genetics
Zhao et al. (2001) analyzed 5 autosomal dominant hereditary spastic paraplegia kindreds showing linkage to the SPG3A locus on 14q. They identified an obligate recombinant individual, permitting a reduction of the interval containing the SPG3A locus to 2.7 cM, and screened candidate genes in this interval for disease-causing mutations (Rainier et al., 2001). Zhao et al. (2001) reported the identification of disease-specific missense mutations in a novel gene, SPG3A (ATL1; 606439), in affected individuals from these 5 SPG3A-linked kindreds. SPG3A is expressed predominantly in the central nervous system. It does not have homology to genes that cause other forms of HSP. By contrast, the peptide encoded by SPG3A, termed atlastin, shows significant homology with several GTPases, particularly guanylate-binding protein-1 (GBP1; 600411), which maps to chromosome 1 and is a member of the dynamin family of large GTPases. The hereditary spastic paraplegia in the families of the SPG3A variety is characterized by early onset (before age 10 and usually before age 5 years).
In an Italian family with HSP characterized by a mean age of onset of 8.3 years and progressive lower extremity weakness and spasticity, Muglia et al. (2002) identified a mutation in the ATL1 gene (606439.0004), which resulted in an arg217-to-gln substitution in a conserved area of GTPases.
Abel et al. (2004) identified mutations in the ATL1 gene (see, e.g., 606439.0001) in affected members of the families reported by Hazan et al. (1993) and Gispert et al. (1995).
Namekawa et al. (2006) stated that 19 mutations in the ATL1 gene had been identified in 40 different families. More than 90% of the mutations were located in exons 4 (12.5%), 7 (27.5%), 8 (17.5%), and 12 (35%). They identified mutations in the ATL1 gene in 7 (13.5%) of 52 families with autosomal dominant SPG with onset before age 20 years and 7 (31.8%) of 22 families with onset before age 10 years. Among a total of 106 mostly European families, no ATL1 mutations were identified in patients with onset after age 10 years. ATL1 mutations were twice as frequent as SPAST (604277) mutations in patients with onset before age 10 years.
Rainier et al. (2006) stated that SPG3A accounts for approximately 10% of dominantly inherited, uncomplicated SPG.
Ivanova et al. (2007) identified 12 different heterozygous ATL1 mutations in 12 (6.6%) of 182 European or Australian probands with spastic paraplegia. Seven mutations were novel, and 3 were de novo.
INHERITANCE \- Autosomal dominant GENITOURINARY Bladder \- Urinary urgency \- Urinary incontinence \- Sphincter disturbances SKELETAL Spine \- Scoliosis Feet \- Pes cavus in patients with early onset NEUROLOGIC Central Nervous System \- Delayed motor development \- Lower limb spasticity \- Lower limb weakness \- Lower limb atrophy \- Spastic gait \- Upper limbs may show mild involvement \- Hyperreflexia \- Extensor plantar responses \- Mental retardation, mild (1 family) \- Thin corpus callosum (1 family) Peripheral Nervous System \- Decreased vibratory sense in lower limbs after long disease duration \- Degeneration of the lateral corticospinal tracts MISCELLANEOUS \- Usually shows early age at onset (range 1 to 7 years, mean 4.6 years) \- Later onset has been rarely reported (up to age 68 years) \- Most patients need assistance walking or are wheelchair-bound \- Insidious onset \- Highly variable severity \- Variable progression \- Reduced penetrance \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the atlastin gene (SPG3A, 606439.0001 ) ▲ 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
|
SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT
|
c2931355
| 8,232 |
omim
|
https://www.omim.org/entry/182600
| 2019-09-22T16:34:42 |
{"doid": ["0110791"], "mesh": ["C536864"], "omim": ["182600"], "orphanet": ["100984"], "synonyms": ["Alternative titles", "SPG3", "STRUMPELL DISEASE", "FAMILIAL SPASTIC PARAPLEGIA, AUTOSOMAL DOMINANT, 1"], "genereviews": ["NBK45978"]}
|
A rare, genetic disorder of urea cycle metabolism and ammonia detoxification characterized by either a severe, neonatal-onset disease found mainly in males, or later-onset (partial) forms of the disease. Both present with episodes of hyperammonemia that can be fatal and which can lead to neurological sequelae.
## Epidemiology
Ornithine transcarbamylase deficiency (OTCD) is the most common type of urea cycle disorder. Worldwide prevalence estimates range between 1/56,500 to 1/113,000 live births.
## Clinical description
Males with the severe, neonatal-onset type are normal at birth but develop poor sucking, hypotonia and lethargy after a few days, rapidly progressing into somnolence and coma. Seizures and hyperventilation may also be present. If untreated, severe encephalopathy will develop with a high risk for death. Patients with a milder form can present at any age. In infants, symptoms can be induced when switching from breast milk to whole milk. In children and adults, environmental stressors (i.e. fasting, high protein diet, pregnancy and the postpartum period, intercurrent illness, surgery) can trigger episodes of hyperammonemic encephalopathy along with nausea, vomiting, headaches, erratic behavior, delirium and combativeness. These episodes can also result in hyperammonemic coma. Neurological complications of hyperammonemic coma include developmental delay and, sometimes, severe cognitive impairment. Many female carriers are asymptomatic; however, they can be affected to the same extent as males if the degree of X-inactivation of the disease allele is unfavorable. Coagulopathy is a frequent finding during metabolic decompensation and sometimes evolves into acute liver failure.
## Etiology
OTCD is due to mutations in the OTC gene (Xp21.1) which encodes OTC, responsible for catalyzing the synthesis of citrulline (in liver and small intestine) from carbamoyl phosphate and ornithine. Mutations that abolish OTC activity completely result in the severe, neonatal-onset form while mutations leading to decreased OTC activity result in the late-onset phenotypes.
## Diagnostic methods
Diagnosis is based on clinical manifestations and plasma ammonia levels are typically high (>200 µmol/L) when encephalopathy is present. Plasma amino acid analysis reveals low citrulline and arginine levels and high glutamine. Urine organic acid analysis usually reveals elevated orotic acid levels. Molecular genetic testing confirms diagnosis.
## Differential diagnosis
Differential diagnoses include carbamoyl-phosphate synthetase deficiency, argininosuccinic aciduria, hyperammonemia due to N-acetylglutamate synthase deficiency, citrullinemia type 1 and argininemia.
## Antenatal diagnosis
Prenatal diagnosis is possible in families with a known disease causing mutation.
## Genetic counseling
OTCD is inherited in an X-linked manner. Where the female parent is a carrier, male offspring have a 50% risk of inheriting the disease. Where the male is affected, male offspring are unaffected and females are obligate carriers. Female heterozygotes may be symptomatic due to skewed X-chromosome inactivation.
## Management and treatment
Patients presenting with a hyperammonemic coma must be treated immediately in a tertiary care center where plasma ammonia levels must be lowered (by hemodialysis or hemofiltration methods), ammonia scavenger therapy implemented, catabolism reversed (through glucose and lipid infusions) and special care taken to reduce the risk of neurological damage (electroencephalogram surveillance and treatment of seizures if necessary). Long-term therapy involves life-long restriction of protein intake and nitrogen scavenger therapy (with sodium benzoate and/or sodium or glycerol phenylbutyrate). A liver transplantation may also be considered in patients with severe, neonatal-onset OTCD (usually performed by 3-6 months of age) or those with frequent hyperammonemic episodes. Valproate, haloperidol, fasting and known stressors should be avoided. Pregnant women with OTCD should be carefully monitored, especially also in the postpartum period.
## Prognosis
Prognosis depends on disease severity but is considered bleak in patients with early neonatal disease. Without early diagnosis and treatment of hyperammonemic episodes, the neurological outcome is poor.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ornithine transcarbamylase deficiency
|
c0268542
| 8,233 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=664
| 2021-01-23T18:27:57 |
{"gard": ["8391"], "mesh": ["D020163"], "omim": ["311250"], "umls": ["C0268542"], "icd-10": ["E72.4"], "synonyms": ["OCT deficiency", "OTC deficiency", "Ornithine carbamoyltransferase deficiency"]}
|
Caustic ingestion
SpecialtyGastroenterology, Intensive care medicine, Pulmonology
SymptomsPain, drooling, vomiting, bleeding, mouth and tongue swelling, eye irritation[1]
ComplicationsEsophageal stricture, esophageal cancer, aspiration pneumonia[1][2]
Usual onsetImmediate
PreventionSafe storage of caustic substances[3]
TreatmentSurgery, medications, observation [1]
Caustic ingestion occurs when someone accidentally or deliberately ingests a caustic or corrosive substance. Depending on the nature of the substance, the duration of exposure and other factors it can lead to varying degrees of damage to the oral mucosa, the esophagus, and the lining of the stomach.[4]
The severity of the injury can be determined by endoscopy of the upper digestive tract, although CT scanning may be more useful to determine whether surgery may be required.[4]
During the healing process, strictures of the oesophagus may form, which may require therapeutic dilatation and insertion of a stent.[4]
## Contents
* 1 Signs and symptoms
* 2 Classification
* 3 Pathophysiology
* 4 Treatment
* 5 Epidemiology
* 6 Prevention
* 7 References
## Signs and symptoms[edit]
Immediate manifestations of caustic substance ingestions include erosions of mucosal surfaces of the gastrointestinal tract or airway (which can cause bleeding if the erosions extend to a blood vessel), mouth and tongue swelling, drooling or hypersalivation, nausea, vomiting, dyspnea, dysphonia/aphonia irritation of the eyes and skin.[1][2] Perforation of the esophagus can lead to mediastinitis or perforation of the stomach or bowel can lead to peritonitis[1] Swelling of the airway or laryngospasm can occur leading to compromised breathing. Injuries affecting the respiratory system include aspiration pneumonia and laryngeal sores.[3] Signs of respiratory compromise include stridor and a change in a person's voice.
Later manifestations of caustic substance ingestions include esophageal strictures or stenosis; which can result in chronic pain and malnutrition.[1] Esophageal strictures more commonly occur after more severe mucosal injury, occurring in to 71% and 100% of grade 2b and 3 mucosal lesions respectively.[2] Remote manifestations of caustic ingestions include esophageal cancer. People who have a history of caustic substance ingestion are 1000-3000 times more likely to develop esophageal cancer with most cases occurring 10-30 years after the ingestion.[2]
## Classification[edit]
The severity of injuries to the mucosa of the gastrointestinal tract is commonly rated using the Zargar criteria.[5]
Category Findings
0 Normal examination
1 Mucosal edema and erythema
2a Superficial ulcerations or erosions, friability, blister formation, exudates, hemorrhages
2b Deep ulcerations (either discrete or circumferential) as well as the findings described in 2a
3a Multiple small, scattered areas of necrosis
3b Extensive necrosis
## Pathophysiology[edit]
Acids with a pH of less than 2 or alkalis with a pH above 12 are capable of causing the most extensive injuries in ingestions.[1] Alkalis damage tissue by saponifying fats, leading to liquefaction necrosis which allows the alkalis to reach deeper tissues. Acids denature proteins via coagulation necrosis, this type of necrosis is thought to prevent the acid from reaching deeper tissues.[1][2] Clinically, the pH, concentration, volume of ingested substance in addition to the duration of time in contact with tissue as well as percentage of body surface area involved determine the severity of the injury.[1]
## Treatment[edit]
Common treatments used for toxic substance ingestions are ineffective, or are even harmful, when implemented in ingestions of caustic substances. Clinical attempts to empty the stomach can cause further injuries.[1] Activated charcoal does not neutralize caustics and can also obscure endoscopic visualization.[1] There is no known clinical benefit of neutralization of the caustic substances; neutralization releases heat as well as causing gaseous distention and vomiting, all of which can worsen injuries.[1]
Signs of airway compromise including decreased level of consciousness, stridor, change in voice, inability to control oral secretions necessitate intubation and mechanical ventillation.[1] IV fluids are often needed to maintain hydration and replace insensible water losses.
Endoscopy should be done within the first 24-48 hours of ingestion as subsequent wound softening increases the risk of perforation. [1] Endoscopically inserted nasogastric tubes can serve as a stent to prevent esophageal strictures as well as allow tube feedings.[1] A CT scan, often enchanced with contrast, can also be used to evaluate injuries.[1]
The most common surgical methods of treatment in children include esophageal dilation and esophageal replacement as less commonly implantation of an esophageal stent.[3]
## Epidemiology[edit]
In general, most ingestions in children involve exploratory ingestions of small amounts of caustic substances, with the rare exception being cases of child abuse where larger amounts are often ingested. Caustic ingestions in adults usually involve larger amounts of ingested material during attempts of self harm.[1] Due to the greater amount of material usually ingested; injuries are often more severe in the intentional ingestions of adolescents and adults as compared to those of children.[1] Commonly ingested substances include ammonium hydroxide (found in general cleaner and grease remover), sodium hydroxide or potassium hydroxide (found in drain opener or oven cleaner), sodium hypochlorite (bleach), oxalic acid (metal polish) and hydrochloric acid (toilet bowl cleaner).[1] Storage of caustic substances in water or drink containers is a risk factor for accidental ingestion of these materials, particularly in children.[2] Boys of preschool age are at the greatest risk of accidental caustic ingestion.[3]
## Prevention[edit]
Preventative measures have been recommended that are intended to decrease the risk of accidental ingestion of caustic substances including":[3]
* Keeping caustic substances in locked cabinets or on upper shelves
* Not storing chemical substances in food or drink containers
* Not keeping large amounts of detergent in the home
* Not mentioning a drug as "candy" when giving it as medication
* Keeping the phone number for poison control in the home
* Keeping caustic substances in labelled containers
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s Longo, Dan L.; Hoffman, Robert S.; Burns, Michele M.; Gosselin, Sophie (30 April 2020). "Ingestion of Caustic Substances". New England Journal of Medicine. 382 (18): 1739–1748. doi:10.1056/NEJMra1810769. PMID 32348645.
2. ^ a b c d e f Hall, Alan H.; Jacquemin, Denise; Henny, Danièlle; Mathieu, Laurence; Josset, Patrice; Meyer, Bernard (3 February 2020). "Corrosive substances ingestion: a review". Critical Reviews in Toxicology. 49 (8): 637–669. doi:10.1080/10408444.2019.1707773. PMID 32009535.
3. ^ a b c d e Rafeey, Mandana; Ghojazadeh, Morteza; Sheikhi, Saeede; Vahedi, Leila (1 September 2016). "Caustic Ingestion in Children: a Systematic Review and Meta-Analysis". Journal of Caring Sciences. 5 (3): 251–265. doi:10.15171/jcs.2016.027. PMC 5045959. PMID 27757390.
4. ^ a b c Chirica, Mircea; Bonavina, Luigi; Kelly, Michael D; Sarfati, Emile; Cattan, Pierre (2017). "Caustic ingestion". The Lancet. 389 (10083): 2041–2052. doi:10.1016/S0140-6736(16)30313-0. PMID 28045663.
5. ^ Ali Zargar, Showkat; Kochhar, Rakesh; Mehta, Saroj; Kumar Mehta, Satish (March 1991). "The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns". Gastrointestinal Endoscopy. 37 (2): 165–169. doi:10.1016/S0016-5107(91)70678-0. PMID 2032601.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Caustic ingestion
|
c0267097
| 8,234 |
wikipedia
|
https://en.wikipedia.org/wiki/Caustic_ingestion
| 2021-01-18T18:58:16 |
{"umls": ["C0267097"], "wikidata": ["Q30314985"]}
|
BRCA2 hereditary breast and ovarian cancer syndrome (BRCA2 HBOC) is an inherited condition that is characterized by an increased risk for a variety of different cancers. Women with this condition have a 49-55% risk of developing breast cancer, a 16-18% risk of developing ovarian cancer and a 62% risk of developing contralateral breast cancer by age 70. Men have a 6% lifetime risk of breast cancer and an increased risk for prostate cancer. Both men and women with BRCA2 HBOC have an elevated risk for pancreatic cancer. BRCA2 HBOC may also be associated with cancers of the stomach, gallbladder, bile duct, esophagus, stomach, fallopian tube, primary peritoneum, and skin; however, these risks are not well defined. This condition is caused by changes (mutations) in the BRCA2 gene and is inherited in an autosomal dominant manner. Management may include high risk cancer screening, chemopreventation and/or prophylactic surgeries.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
BRCA2 hereditary breast and ovarian cancer syndrome
|
c0677776
| 8,235 |
gard
|
https://rarediseases.info.nih.gov/diseases/12352/brca2-hereditary-breast-and-ovarian-cancer-syndrome
| 2021-01-18T18:01:43 |
{"mesh": ["D061325"], "orphanet": ["145"], "synonyms": ["HBOC", "Familial susceptibility to breast-ovarian cancer 2", "BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2, INCLUDED", "OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2, INCLUDED", "Breast-ovarian cancer, familial 2", "BRCA2 Hereditary Breast and Ovarian Cancer; Breast cancer, familial 2", "BROVCA2"]}
|
Renal cortical necrosis
Other namesDiffuse bilateral renal cortical necrosis (BRCN), diffuse cortical necrosis, acute cortical necrosis, acute kidney failure with acute cortical necrosis
SpecialtyNephrology
Renal cortical necrosis (RCN) is a rare cause of acute kidney failure. The condition is "usually caused by significantly diminished arterial perfusion of the kidneys due to spasms of the feeding arteries, microvascular injury, or disseminated intravascular coagulation" and is the pathological progression of acute tubular necrosis.[1] It is frequently associated with obstetric catastrophes such as abruptio placentae and septic shock, and is three times more common in developing nations versus industrialized nations (2% versus 6% in causes of acute kidney failure).[citation needed]
## Contents
* 1 Causes
* 1.1 Adults
* 1.2 Babies
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 References
* 7 External links
## Causes[edit]
### Adults[edit]
* Pregnancy related (>50% of cases)
* Placental abruption
* Infected abortion
* Prolonged intrauterine fetal death
* Severe eclampsia
* HIV[2]
* Snake bites[3]
* Binge drinking[4]
* Shock
* Trauma
* Sickle cell disease[5]
* Systemic lupus erythematosus (SLE)[6]
* Sepsis[7]
* SLE-associated antiphospholipid syndrome[8]
* Vitamin deficiency[9]
* Pancreatitis[10]
* Malaria[11]
* Meningococcemia[12]
* Drug-induced toxicity (e.g. NSAIDs, Contrast Media, Quinine,[13] or ATRA[14])
### Babies[edit]
* Congenital heart disease
* Fetal-maternal transfusion
* Dehydration
* Perinatal asphyxia
* Anemia
* Placental hemorrhage
* Severe hemolytic disease
* Sepsis[7]
## Pathophysiology[edit]
The exact pathologic mechanism for RCN is unclear, however the onset of small vessel pathology is likely an important aspect in the cause of this condition. In general the renal cortex is under greater oxygen tension and more prone to ischemic injury, especially at the level of the proximal collecting tubule, leading to its preferential damage in a sudden drop in perfusion. Rapidly corrected acute renal ischemia leads to acute tubular necrosis, from which complete recovery is possible, while more prolonged ischemia may lead to RCN. Pathologically, the cortex of the kidney is grossly atrophied with relative preservation of the gross structure of the medulla. The damage is usually bilateral owing to its underlying systemic causes, and is most frequently associated with pregnancy (>50% of cases).[1] It accounts for 2% of all cases of acute kidney failure in adults and more than 20% of cases of acute kidney failure during late pregnancy.[15][16]
## Diagnosis[edit]
While the only diagnostic "gold standard" mechanism of diagnosis en vivo is via kidney biopsy, the clinical conditions and blood clotting disorder often associated with this disease may make it impractical in a clinical setting. Alternatively, it is diagnosed clinically, or at autopsy, with some authors suggesting diagnosis by contrast enhanced CT.[17]
## Treatment[edit]
Patients will require dialysis to compensate for the function of their kidneys.
## Prognosis[edit]
This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (March 2012) (Learn how and when to remove this template message)
Cortical necrosis is a severe and life-threatening condition, with mortality rates over 50%.[citation needed] Those mortality rates are even higher in neonates with the condition due to the overall difficult nature of neonatal care and an increased frequency of comorbid conditions. The extent of the necrosis is a major determinant of the prognosis, which in turn is dependent on the duration of ischemia, duration of oliguria, and the severity of the precipitating conditions. Of those that survive the initial event, there are varying degrees of recovery possible, depending on the extent of the damage.
## References[edit]
1. ^ a b Deverajan, Prasad (May 26, 2011). Langman, Craig B (ed.). "eMedicine: Renal Cortical Necrosis". Medscape. Retrieved 27 March 2012.
2. ^ Singh, B.; Gupta, A.; Mahajan, S.; Gupta, R. (2012). "Acute cortical necrosis and collapsing glomerulopathy in an HIV-infected patient: A rare clinical scenario". Saudi Journal of Kidney Diseases and Transplantation. 23 (2): 363–366. PMID 22382240.
3. ^ Kumar, S.; Sharma, A.; Sodhi, K. S.; Wanchu, A.; Khandelwal, N.; Singh, S. (2012). "Renal cortical necrosis, peripheral gangrene, perinephric and retroperitoneal haematoma in a patient with a viper bite". Tropical Doctor. 42 (2): 116–117. doi:10.1258/td.2011.110281. PMID 22316624.
4. ^ Jung, Y. S.; Shin, H. S.; Rim, H.; Jang, K.; Park, M. H.; Park, J. -S.; Lee, C. -H.; Kim, G. -H.; Kang, C. M. (2012). "Bilateral Renal Cortical Necrosis Following Binge Drinking". Alcohol and Alcoholism. 47 (2): 140–142. doi:10.1093/alcalc/agr154. PMID 22215004.
5. ^ Jha, R.; Narayan, G.; Swarnalata, G.; Shiradhonkar, S.; Rao, B. S.; Sinha, S. (2011). "Acute cortical necrosis following renal transplantation in a case of sickle cell trait". Indian Journal of Nephrology. 21 (4): 286–288. doi:10.4103/0971-4065.78066. PMC 3193676. PMID 22022093.
6. ^ Uppin, M. S.; Rajasekhar, L.; Swetha, H.; Srinivasan, V. R.; Prayaga, A. K. (2010). "Renal cortical necrosis at presentation in a patient with systemic lupus erythematosus: An autopsy case report". Clinical Rheumatology. 29 (7): 815–818. doi:10.1007/s10067-010-1395-5. PMID 20169460.
7. ^ a b Huang, C. C.; Huang, J. K. (2011). "Sepsis-Induced Acute Bilateral Renal Cortical Necrosis". Nephrology. 16 (8): 787. doi:10.1111/j.1440-1797.2011.01478.x. PMID 22029648.
8. ^ Kim, J. O.; Kim, G. H.; Kang, C. M.; Park, J. S. (2011). "Bilateral Acute Renal Cortical Necrosis in SLE-Associated Antiphospholipid Syndrome". American Journal of Kidney Diseases. 57 (6): 945–947. doi:10.1053/j.ajkd.2011.02.381. PMID 21514023.
9. ^ Novembrino, C.; De Giuseppe, R.; De Liso, F.; Bonara, P.; Bamonti, F. (2010). "Vitamin deficiency and renal cortical necrosis". The Lancet. 376 (9736): 160. doi:10.1016/S0140-6736(10)61101-4. PMID 20638557.
10. ^ Kumar, S.; Krishna, G. S.; Kishore, K. C.; Sriram, N. P.; Sainaresh, V. V.; Lakshmi, A. Y. (2009). "Bilateral renal cortical necrosis in acute pancreatitis". Indian Journal of Nephrology. 19 (3): 125. doi:10.4103/0971-4065.57112. PMC 2859480. PMID 20436735.
11. ^ Baliga, K. V.; Narula, A. S.; Khanduja, R.; Manrai, M.; Sharma, P.; Mani, N. S. (2008). "Acute Cortical Necrosis inFalciparumMalaria: An Unusual Manifestation". Renal Failure. 30 (4): 461–463. doi:10.1080/08860220801964293. PMID 18569922.
12. ^ Toh, H. -S.; Cheng, K. -C.; Kuar, W. -K.; Tan, C. -K. (2008). "The Case ∣ Generalized petechiae and acute renal failure". Kidney International. 73 (12): 1443–1444. doi:10.1038/ki.2008.143. PMID 18516063.
13. ^ Leroy, F.; Bridoux, F.; Abou-Ayache, R.; Belmouaz, S.; Desport, E.; Thierry, A.; Bauwens, M.; Touchard, G. (2008). "Nécrose corticale rénale bilatérale induite par la quinine". Néphrologie & Thérapeutique. 4 (3): 181–186. doi:10.1016/j.nephro.2008.01.001. PMID 18343736.
14. ^ Sastre López, A.; Gago González, E.; Baños Gallardo, M.; Gómez-Huertas, E.; Ortega Suárez, F. (2007). "All-trans retinoic acid syndrome corrected and renal cortical necrosis". Anales de Medicina Interna (Madrid, Spain : 1984). 24 (11): 551–553. doi:10.4321/s0212-71992007001100009. PMID 18275266.
15. ^ Prakash, J.; Niwas, S. S.; Parekh, A.; Pandey, L. K.; Sharatchandra, L.; Arora, P.; Mahapatra, A. K. (2010). "Acute kidney injury in late pregnancy in developing countries". Renal Failure. 32 (3): 309–313. doi:10.3109/08860221003606265. PMID 20370445.
16. ^ Pertuiset, N.; Grünfeld, J. P. (1994). "Acute renal failure in pregnancy". Baillière's Clinical Obstetrics and Gynaecology. 8 (2): 333–351. doi:10.1016/s0950-3552(05)80324-4. PMID 7924011.
17. ^ Kim, H. J.; Cho, O. K. (1996). "CT scan as an important diagnostic tool in the initial phase of diffuse bilateral renal cortical necrosis". Clinical Nephrology. 45 (2): 125–130. PMID 8846525.
## External links[edit]
Classification
D
* ICD-10: N17.1
* ICD-9-CM: 583.6
* MeSH: D007673
* SNOMED CT: 444691002
* 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]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing 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 cortical necrosis
|
c0022656
| 8,236 |
wikipedia
|
https://en.wikipedia.org/wiki/Renal_cortical_necrosis
| 2021-01-18T19:01:19 |
{"mesh": ["D007673"], "umls": ["C0022656"], "icd-9": ["583.6"], "wikidata": ["Q2860302"]}
|
A number sign (#) is used with this entry because hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2) is caused by heterozygous mutation in the SLC9A3R1 gene (604990) on chromosome 17q25.1.
See also NPHLOP1 (612286), caused by mutation in the SLC34A1 gene (182309).
Clinical Features
Karim et al. (2008) reported 4 unrelated probands with hypophosphatemia and decreased renal phosphate resorption. Three of the patients had calcium nephrolithiasis, and 1 had a spinal deformity and decreased bone mineral density (BMD). All had significantly decreased tubular maximum for phosphate resorption per glomerular filtration rate (TmP/GFR) values compared to normal, indicating impaired proximal renal tubular phosphate absorption. None of the patients had proximal-tubule dysfunction other than the low TmP/GFR value; they did not have glycosuria, and serum bicarbonate concentrations and blood pH values were normal. Other biochemical findings included increased urinary cAMP excretion and increased serum 1,25-dihydroxyvitamin D (calcitriol).
Molecular Genetics
In 4 of 92 unrelated patients with calcium-containing renal stones (50 patients), bone demineralization (30), or both (12), Karim et al. (2008) identified heterozygous mutations in the SLC9A3R1 gene (604990.0001-604990.0003). In vitro studies indicated that the mutations had no effect on basal phosphate uptake but potentiated parathyroid hormone (PTH; 168450)-induced AMP generation and the inhibition of phosphate transport. The results demonstrated that mutations in the SLC9A3R1 gene can cause renal phosphate loss that may increase the risk of renal stone formation or bone demineralization.
INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Nephrolithiasis \- Renal phosphate wasting SKELETAL \- Osteopenia \- Osteoporosis \- Increased susceptibility to fractures Spine \- Spinal deformity LABORATORY ABNORMALITIES \- Hypophosphatemia \- Hyperphosphaturia \- Increased serum 1,25-dihydroxyvitamin D MOLECULAR BASIS \- Caused by mutation in the solute carrier family 9, isoform A3, regulatory factor 1 gene (SLC9A3R1, 604990.0001 ) ▲ 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
|
NEPHROLITHIASIS/OSTEOPOROSIS, HYPOPHOSPHATEMIC, 2
|
c2676782
| 8,237 |
omim
|
https://www.omim.org/entry/612287
| 2019-09-22T16:01:56 |
{"doid": ["0080078"], "mesh": ["C567362"], "omim": ["612287"], "orphanet": ["244305"], "synonyms": []}
|
IPEX syndrome
Other namesAutoimmune enteropathy type 1[1]
IPEX syndrome is inherited via X-linked recessive
SpecialtyImmunology
SymptomsLymphadenopathy[2]
CausesFOXP3 gene mutation[1]
Diagnostic methodFamily history, Genetic test[1]
TreatmentTPN(nutritional purpose), Cyclosporin A and FK506, Bone marrow transplant[3][4]
Immunodysregulation polyendocrinopathy enteropathy X-linked (or IPEX) syndrome is a rare disease linked to the dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the regulatory T cell lineage.[5][6] It leads to the dysfunction of regulatory T-cells and the subsequent autoimmunity.[7] The disorder is one of the autoimmune polyendocrine syndromes and manifests with autoimmune enteropathy, psoriasiform or eczematous dermatitis, nail dystrophy, autoimmune endocrinopathies, and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid.[7][2] Management for IPEX has seen limited success in treating the syndrome by bone marrow transplantation.[8]
## Contents
* 1 Symptoms and signs
* 2 Genetics
* 3 Mechanism
* 4 Diagnosis
* 5 Treatment
* 6 Research
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Symptoms and signs[edit]
Eczema
Some of the symptoms and signs of IPEX syndrome are the following:[2]
* Lymphadenopathy
* Eczema
* Hypothyroidism
* Diarrhea
## Genetics[edit]
Mutations in FOXP3 gene causing IPEX syndrome - known in year 2012.
IPEX syndrome is inherited in males via an x-linked recessive manner, as the FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of this condition.[5][6]
Mutation of FOXP3 leading to expression of malfunctioning protein is often localised in DNA-binding domain called the forkhead domain. The truncated protein can not bind to its binding-spot on the DNA and thus its function concerning T regulatory lymphocytes development and functioning is impaired. The absence or dysfunction of regulatory T cells is the cause of autoimmune symptoms.[9]
Data from 2018 describes over 70 mutations in FOXP3 gene leading to IPEX syndrome. Nonetheless, this number is still changing with new cases and discoveries coming.[10] For example in 2010 there were only 20 mutations of FOXP3 known in the literature.[9]
## Mechanism[edit]
This autoimmunity called IPEX is an attack from the body's own immune system against the body's own tissues and organs.[4] Early age onset of this disease in males causes severe enlargement of the secondary lymphoid organs, and insulin dependent diabetes[medical citation needed]
This condition indicates the loss of CD4+ CD25+ T regulatory cells, and express the transcription factor Foxp3. Foxp3 decrease is a consequence of unchecked T cell activation, which is secondary to loss of regulatory T cells.[11]
## Diagnosis[edit]
The diagnosis of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is consistent with the following criteria:[1]
* Clinical examination
* Family history
* Laboratory findings
* Genetic testing
## Treatment[edit]
FK506(Tacrolimus)
In terms of treatment the following are done to manage the IPEX syndrome in those affected individuals (corticosteroids are the first treatment that is used):[4][3]
* TPN (nutritional purpose)
* Cyclosporin A and FK506
* Sirolimus (should FK506 prove non-effective)
* Granulocyte colony stimulating factor
* Bone marrow transplant
* Rituximab
## Research[edit]
There is as well a special mouse model simulating the development and progression of the IPEX syndrome. The model mice are called "scurfy mice" and they have had 2 base pairs inserted within the Foxp3 gene. Consequently, this leads to a frameshift and the expressed protein is truncated, causing the same effects as FOXP3 mutation in humans. The mice suffer from enlarged spleen and lymph nodes, redness in eyes, and skin abnormalities. The mice as well suffer from immunity problems and after approximately 3 weeks they die.[10]
## See also[edit]
* Autoimmune polyendocrine syndrome
* FOXP3
* Autoimmune polyendocrine syndrome type 2
## References[edit]
1. ^ a b c d RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Immune dysregulation polyendocrinopathy enteropathy X linked syndrome". www.orpha.net. Retrieved 2017-04-18.
2. ^ a b c "Immunodysregulation, polyendocrinopathy and enteropathy X-linked | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-04-16.
3. ^ a b Eisenbarth, George S. (2010-12-13). Immunoendocrinology: Scientific and Clinical Aspects. Springer Science & Business Media. pp. 129–138. ISBN 9781603274784.
4. ^ a b c Hannibal, Mark C.; Torgerson, Troy (1993-01-01). "IPEX Syndrome". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Ledbetter, Nikki; Mefford, Heather C. (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301297.update 2011
5. ^ a b Reference, Genetics Home. "IPEX syndrome". Genetics Home Reference. Retrieved 2017-04-16.
6. ^ a b Reference, Genetics Home. "FOXP3 gene". Genetics Home Reference. Retrieved 2017-04-16.
7. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 72. ISBN 978-1-4160-2999-1.
8. ^ Wildin RS, Smyk-Pearson S, Filipovich AH (August 2002). "Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome". J Med Genet. 39 (8): 537–45. doi:10.1136/jmg.39.8.537. PMC 1735203. PMID 12161590.
9. ^ a b Michels, Aaron W.; Gottlieb, Peter A. (2010). "Autoimmune polyglandular syndromes". Nature Reviews Endocrinology. 6 (5): 270–277. doi:10.1038/nrendo.2010.40. ISSN 1759-5029. PMID 20309000. S2CID 20395564.
10. ^ a b Bacchetta, Rosa; Barzaghi, Federica; Roncarolo, Maria-Grazia (2018). "From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation: IPEX syndrome and FOXP3". Annals of the New York Academy of Sciences. 1417 (1): 5–22. doi:10.1111/nyas.13011. PMID 26918796.
11. ^ Verbsky, James W.; Chatila, Talal A. (2017-04-18). "Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-Related Disorders: an Evolving Web of Heritable Autoimmune Diseases". Current Opinion in Pediatrics. 25 (6): 708–714. doi:10.1097/MOP.0000000000000029. ISSN 1040-8703. PMC 4047515. PMID 24240290.
## Further reading[edit]
* Bacchetta, Rosa; Barzaghi, Federica; Roncarolo, Maria-Grazia (25 February 2016). "From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation". Annals of the New York Academy of Sciences. 1417 (1): 5–22. doi:10.1111/nyas.13011. ISSN 1749-6632. PMID 26918796.
* Barzaghi, Federica; Passerini, Laura; Bacchetta, Rosa (1 January 2012). "Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity". Frontiers in Immunology. 3: 211. doi:10.3389/fimmu.2012.00211. ISSN 1664-3224. PMC 3459184. PMID 23060872.
* Elzouki, A. Y.; Harfi, H. A.; Nazer, H.; Stapleton, F. B.; Oh, William; Whitley, R. J. (2012-01-10). Textbook of Clinical Pediatrics. Springer Science & Business Media. ISBN 9783642022029.
## External links[edit]
* PubMed
Classification
D
* ICD-10: E31.0
* OMIM: 304790
* MeSH: C580192
* DiseasesDB: 33417
External resources
* GeneReviews: IPEX Syndrome
* Orphanet: 37042
Scholia has a topic profile for IPEX syndrome.
* v
* t
* e
X-linked disorders
X-linked recessive
Immune
* Chronic granulomatous disease (CYBB)
* Wiskott–Aldrich syndrome
* X-linked severe combined immunodeficiency
* X-linked agammaglobulinemia
* Hyper-IgM syndrome type 1
* IPEX
* X-linked lymphoproliferative disease
* Properdin deficiency
Hematologic
* Haemophilia A
* Haemophilia B
* X-linked sideroblastic anemia
Endocrine
* Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
* KAL1 Kallmann syndrome
* X-linked adrenal hypoplasia congenita
Metabolic
* Amino acid: Ornithine transcarbamylase deficiency
* Oculocerebrorenal syndrome
* Dyslipidemia: Adrenoleukodystrophy
* Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
* Pyruvate dehydrogenase deficiency
* Danon disease/glycogen storage disease Type IIb
* Lipid storage disorder: Fabry's disease
* Mucopolysaccharidosis: Hunter syndrome
* Purine–pyrimidine metabolism: Lesch–Nyhan syndrome
* Mineral: Menkes disease/Occipital horn syndrome
Nervous system
* X-linked intellectual disability: Coffin–Lowry syndrome
* MASA syndrome
* Alpha-thalassemia mental retardation syndrome
* Siderius X-linked mental retardation syndrome
* Eye disorders: Color blindness (red and green, but not blue)
* Ocular albinism (1)
* Norrie disease
* Choroideremia
* Other: Charcot–Marie–Tooth disease (CMTX2-3)
* Pelizaeus–Merzbacher disease
* SMAX2
Skin and related tissue
* Dyskeratosis congenita
* Hypohidrotic ectodermal dysplasia (EDA)
* X-linked ichthyosis
* X-linked endothelial corneal dystrophy
Neuromuscular
* Becker's muscular dystrophy/Duchenne
* Centronuclear myopathy (MTM1)
* Conradi–Hünermann syndrome
* Emery–Dreifuss muscular dystrophy 1
Urologic
* Alport syndrome
* Dent's disease
* X-linked nephrogenic diabetes insipidus
Bone/tooth
* AMELX Amelogenesis imperfecta
No primary system
* Barth syndrome
* McLeod syndrome
* Smith–Fineman–Myers syndrome
* Simpson–Golabi–Behmel syndrome
* Mohr–Tranebjærg syndrome
* Nasodigitoacoustic syndrome
X-linked dominant
* X-linked hypophosphatemia
* Focal dermal hypoplasia
* Fragile X syndrome
* Aicardi syndrome
* Incontinentia pigmenti
* Rett syndrome
* CHILD syndrome
* Lujan–Fryns syndrome
* Orofaciodigital syndrome 1
* Craniofrontonasal dysplasia
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
IPEX syndrome
|
c0342288
| 8,238 |
wikipedia
|
https://en.wikipedia.org/wiki/IPEX_syndrome
| 2021-01-18T18:51:18 |
{"gard": ["1850"], "mesh": ["C580192"], "umls": ["C1844663", "C0342288"], "orphanet": ["37042"], "wikidata": ["Q3508566"]}
|
A number sign (#) is used with this entry because spinocerebellar ataxia-6 (SCA6) is caused by heterozygous mutation in the CACNA1A gene (601011) on chromosome 19p13.
The most common mutation is an expanded CAG(n) repeat in exon 47 of the CACNA1A gene (601011.0007). Normal alleles contain 4 to 18 repeats, whereas pathogenic alleles contain 19 to 33 repeats (Li et al., 2009).
For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Clinical Features
Subramony et al. (1996) described a family segregating late-onset progressive cerebellar ataxia with onset of gait difficulties at age 50. There was no pontine atrophy at autopsy nor was there evidence of hypogonadism. The segregation appeared to be autosomal dominant with multiple instances of male-to-male transmission. Direct DNA analysis excluded expansions at the SCA1 (164400), Machado-Joseph (607047), and DRPLA (125370) loci.
Zhuchenko et al. (1997) reported 8 unrelated families who showed a very similar clinical picture consisting predominantly of mild but slowly progressive cerebellar ataxia of the limbs and gait, dysarthria, nystagmus, and mild vibratory and proprioceptive sensory loss. The disease is insidious and most patients do not realize they are affected initially but do describe a sense of momentary imbalance and 'wooziness' when they make a quick turn or a rapid movement. Typically, it is years after this initial sensation when the patients realize they have developed balance and coordination difficulties. The disease usually progresses over 20 to 30 years, leading to impairment of gait and causing the patient to become wheelchair-bound. In a few older patients, choking has been observed, suggesting involvement of the brainstem. The disease was the cause of death in several members of 2 kindreds. Magnetic resonance imaging (MRI) of the brain in affected individuals demonstrated isolated cerebellar atrophy. By genotype survey, Zhuchenko et al. (1997) found a CAG repeat expansion in the CACNA1A gene (see MOLECULAR GENETICS).
The clinical and genetic features of 38 genetically confirmed cases of SCA6 from 8 families were described by Ishikawa et al. (1997). Gait ataxia was invariably the initial symptom and was the chief symptom throughout the clinical course. Other symptoms were cerebellar speech, limb ataxia, decreased muscle tonus, and horizontal gaze nystagmus. Tendon reflexes were normal or slightly increased. Extracerebellar symptoms, such as pyramidal or extrapyramidal tract signs, ophthalmoparesis, or decreased sensation, were not seen. None of the patients complained of migraine. Magnetic resonance imaging demonstrated atrophy restricted to the cerebellum. The age at onset ranged from 20 to 66 years, and the average age at onset was 45 years.
Gomez et al. (1997) described clinical, genetic, neuroimaging, neuropathologic, and quantitative oculomotor studies in 4 kindreds with genotypically confirmed SCA6. The age of onset of ataxia ranged from 24 to 63 years among affected individuals. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of oculomotor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibuloocular reflex. In 2 of the kindreds, they found strong linkage to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles, which were a single size in the 2 kindreds (22 and 23 units). These studies identified a distinct phenotype associated with SCA6, just as SCA7 (164500) is associated with retinopathy and blindness, and SCA2 (183090) is associated with pronounced slowing or loss of saccadic eye movements. One of the families in which the expanded CAG repeat was identified was the family previously reported by Zee et al. (1976).
Schols et al. (1998) studied 9 German families with spinocerebellar ataxia-6 and found that the phenotype comprised predominantly cerebellar signs in accord with isolated cerebellar atrophy on MRI. Noncerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of autosomal dominant cerebellar ataxia. Although age at onset correlated inversely with CAG repeat length, other clinical signs and progression rate did not. By comparison with SCA1, SCA2, and SCA3, no clinical or electrophysiologic findings were specific for SCA6. Moreover, the molecular defect could not be predicted from clinical investigations.
Fukutake et al. (2002) described a 55-year-old man, the offspring of first-cousin parents, who presented not only with cerebellar ataxia and vertical antidirectional nystagmus but also with retinitis pigmentosa. The numbers of CAG repeats in the expanded alleles of the SCA6 gene were 21 on each chromosome. The retinal degeneration was thought to be secondary to a genetic disorder of either autosomal or X-linked recessive inheritance rather than SCA6. The association of retinitis pigmentosa with spinocerebellar ataxia is most characteristic of SCA7 (164500). Both parents had staggering gait and slurred speech late in life, but were not available for study.
In 7 SCA6 patients, van de Warrenburg et al. (2004) found no significant electrophysiologic evidence of peripheral nerve involvement.
### Pathologic Findings
Tsuchiya et al. (1998) described a Japanese family with 2 affected sisters and an affected father. The proband developed gait disturbance at age 62 years and died at age 67 years due to subarachnoid hemorrhage. Neuropathologic examination showed severe loss of Purkinje cells in the cerebellum, predominantly in the dorsal vermis, and absence of neuronal loss in the inferior olives. The younger sister developed gait disturbance also at age 62 years. Neuroimaging at the age of 66 years showed cerebellar atrophy, predominantly in the vermis. Tsuchiya et al. (1998) performed a neuropathologic review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy and found 2 patterns in the distribution of cerebellar cortical lesions. The distribution of cerebellar cortical lesions in genetically confirmed Japanese patients with SCA6 was more prominent in the vermis than in the hemisphere.
Takahashi et al. (1998) described a family with dominantly inherited ataxia of late adult onset with affected individuals in 4 generations. Expansion of a CAG repeat in the CACNA1A gene was identified at autopsy in 1 patient, a 65-year-old woman with a disease duration of 11 years. In this patient, pathologic changes were confined to the cerebellar cortex and inferior olivary complex. The cerebellar cortex showed severe loss of Purkinje cells with proliferation of Bergmann glia, more pronounced in the superior parts of the vermis and hemispheres. In the inferior olivary complex, a reduced neuronal cell population, which could be interpreted as a change secondary to the cerebellar cortical lesion, was evident. They concluded that the pathologic phenotype of SCA6 is cerebelloolivary atrophy, or more strictly cerebellar cortical atrophy.
Other Features
Soong et al. (2001) performed positron emission tomography using labeled glucose on 7 patients with SCA6 and 7 healthy controls to elucidate metabolic features of SCA6. They found significant hypometabolism in the patients with SCA6, ranging from 63 to 78% that of controls, in the brainstem, cerebellar hemisphere, basal ganglia, and various areas of the cortex. None of the patients manifested symptoms referable to the basal ganglia or cerebral cortices. Although Soong et al. (2001) postulated that the differences may be due to subclinical neuronal cell dysfunction, variation in regional blood flow, or metabolic dysfunction in structurally intact neurons, they suggested that the findings may indicate that SCA6 is not a purely cerebellar syndrome.
Christova et al. (2008) observed abnormal ocular motor anomalies in 4 presymptomatic SCA6 patients with CACNA1A mutations. Two patients had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks, and a fourth had a reduced gain for pursuit tracking. Multivariate analysis discriminated the presymptomatic patients as a group from healthy controls and 5 manifesting SCA6 patients. Christova et al. (2008) suggested that early functional oculomotor impairments in SCA6 are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus.
Mapping
Ishikawa et al. (1997) carried out genomewide linkage analysis in 15 Japanese families with autosomal dominant pure cerebellar ataxia (ADPCA). Evidence for linkage to chromosome 19p markers was found in 8 families, all of whom showed expansion of a CAG repeat in the CACNA1A gene, and combined multipoint analysis refined the candidate region to a 13.3-cM interval in 19p13.2-p13.1. 6 families were excluded for this region and 1 family was inconclusive.
Pathogenesis
Expansion of repeat sequences involving the trinucleotides CAG, CTG, CGG, or GAA is the primary cause of several dominantly inherited neurologic disorders. Among them, CAG repeat expansions have been associated with Huntington disease (HD; 143100), X-linked spinobulbar muscular atrophy (313200), and several spinocerebellar ataxias. Zhuchenko et al. (1997) noted that the CAG repeat arrays in these diseases are located in the coding region of the involved gene and are translated into polyglutamine tracts in the protein product. It is postulated that an expansion of the polyglutamine tract produces a gain of function in the protein product in each disease, accounting for the dominant inheritance.
Ishikawa et al. (1999) used RT-PCR and in situ hybridization to demonstrate that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of normal human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intranuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The authors concluded that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the alpha-1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A.
Kordasiewicz et al. (2006) found that a 75-kD C-terminal fragment of CACNA1A, which is the location of the polyglutamine tract expanded in SCA6, is cleaved from the full-length protein and translocated to the nucleus, where it is toxic to cells when in the expanded state. The polyglutamine-mediated cell toxicity was dependent on nuclear localization, suggesting that specific processing and localization of the mutant protein is involved in the pathogenesis of SCA6.
Li et al. (2009) confirmed that C-terminal fragments of CACNA1A localized predominantly to the nucleus of HEK293 cells where they existed as speckle-like structures resembling promyelocytic leukemia nuclear bodies (PMLNBs). HEK293 cells expressing an expanded (24 CAG repeats) C-terminal end of CACNA1A showed decreased viability when exposed to toxic cadmium compared to cells with nonexpanded (13 CAG) repeats. However, there were no differences in viability under normal culture conditions. Cadmium treatment also disrupted the PMLNBs and enhanced aggregation of C-terminal CACNA1A fragments, particularly in CAG-expanded cells. Immunocytochemical studies showed that cadmium-induced death was caspase-3 (CASP3; 600636)-dependent, indicating apoptosis. Gene expression studies showed downregulation of the HSF1 (140580)-HSPA1A (140550) axis as an event in 24-CAG repeat cells that appeared to be critical for cellular toxicity. The findings were consistent with SCA6 pathogenesis being related to polyglutamine diseases.
Molecular Genetics
Zhuchenko et al. (1997) performed a genotyping survey using polymorphic CAG repeats and DNA samples from patients with late-onset neurogenic diseases. In the course of these studies they found an expansion of a CAG repeat in the human alpha-1A-voltage-dependent Ca(2+) channel gene (601011.0007), which maps to 19p13. They identified 6 isoforms of the human alpha-1A calcium channel subunit. The CAG repeat was within the open reading frame and was predicted to encode glutamine in 3 of the isoforms. In 8 families, the CAG repeat expansion of the Ca(2+) channel gene was the mutation mechanism for SCA6. One of the families had been reported by Subramony et al. (1996).
Analysis of CAG repeat expansion in the CACNL1A4 gene by Ishikawa et al. (1997) revealed expansion in 8 of 15 Japanese families with autosomal dominant cerebellar ataxia; all affected individuals had larger alleles (range of CAG repeats 21 to 25), compared with alleles observed in neurologically normal Japanese (range 5 to 20 repeats).
Takiyama et al. (1998) studied a Japanese family that included 13 persons with SCA6 in 5 generations. Molecular testing revealed that the patients carried the smallest known expanded CAG repeat (21 repeat units). The clinical features of these patients included predominantly cerebellar ataxia with onset late in adult life and a very slowly progressive course. In addition, this SCA6 family showed some characteristic clinical and genetic features, including (1) apparent lack of genetic anticipation, with an intergenerationally stable CAG repeat size, and (2) down-beat nystagmus and diabetes mellitus in some of the SCA6 patients. They identified 3 individuals homozygous for an expanded CAG repeat (21/21) in the CACNL1A4 gene; 2 were symptomatic and 1 was asymptomatic at age 50 years. There was no apparent difference in clinical phenotype between the homozygotes and the heterozygotes.
Fukutake et al. (2002) stated that 11 patients with genetically verified SCA6 who were homozygous or compound heterozygous for (CAG)n repeats in the CACNA1A gene (601011.0007) had previously been reported.
In a family in which multiple members had severe progressive cerebellar ataxia involving the trunk, extremities, and speech, Yue et al. (1997) identified a 1152G-A transition in exon 6 of the CACNA1A gene, resulting in a gly293-to-arg substitution (G293R; 601011.0009). The CAG(n) repeat expansion associated with SCA6 was not present in any family member.
In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, Alonso et al. (2003) found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; 601011.0018).
### Genetic Anticipation
In his studies of families with SCA6, Zhuchenko et al. (1997) noted that there seemed to be a correlation between the repeat number and earlier onset of the disorder. Matsuyama et al. (1997) analyzed 60 SCA6 individuals from 39 independent Japanese SCA6 families and found that the CAG repeat length in the CACNL1A4 gene was inversely correlated with age of onset. SCA6 chromosomes contained 21 to 30 repeat units, whereas normal chromosomes displayed 6 to 17 repeats. There was no overlap between the normal and affected CAG repeat number. Anticipation was observed clinically in all 8 parent-child pairs examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed an increase in the expansion of CAG repeats only in 1 pair and no diminution in any affected cases. The results suggested that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate unequivocal gene dosage effect on the age of onset.
In the 8 families with SCA6 reported by Ishikawa et al. (1997), inverse correlation between the CAG-repeat number and the age of onset was found in affected individuals with expansion. The number of CAG repeats in expanded chromosomes was completely stable within each family, which was consistent with the fact that anticipation was not statistically proven in these SCA6 families.
Riess et al. (1997) observed the trinucleotide expansion in 4 ataxia patients without obvious family history of the disease, indicating the necessity to search for the SCA6 (CAG)n expansion even in sporadic patients. In their series of 32 patients, onset was usually late and the (CAG)n stretch varied between 22 and 28 trinucleotide units, the shortest trinucleotide repeat expansion causing spinocerebellar ataxia. Analyzing 248 apparently healthy octogenarians, Riess et al. (1997) found 1 allele of 18 repeats, the longest normal CAG repeat in the CACNL1A4 gene reported to that time. They could demonstrate no repeat instability of the expanded allele on transmission and no repeat instability was found for the normal allele in 431 meioses in the CEPH families.
Mariotti et al. (2001) described an Italian family in which 1 member carried a fully expanded SCA6 allele with 26 CAG repeats, whereas the other affected family member was homozygous for an intermediate allele of 19 CAG repeats. Three family members, heterozygous for the intermediate allele, were clinically unaffected. The findings demonstrated a dose-dependent pathogenic effect of an intermediate CAG expansion in the SCA6 gene.
Takahashi et al. (2004) retrospectively analyzed 140 patients with SCA6. They observed an inverse correlation between the age at onset and the length of the expanded allele, and also between the age at onset and the sum of CAG repeats in the normal and the expanded alleles. The ages at onset of 4 homozygous patients correlated better with the sum of CAG repeats in both alleles than with the expanded allele calculated from heterozygous SCA6 patients. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. Neuro-otologic examination performed in 22 patients suggested that the abnormalities of ocular movements were purely cerebellar in nature. There was a close relationship between down-beat positioning nystagmus and positioning vertigo, which became more common in the later stage. Takahashi et al. (2004) concluded that total number of CAG repeat units in both alleles is a good parameter for assessment of age at onset in SCA6, including in homozygous patients. In addition, clinical and neuro-otologic examination suggested that SCA6 is a disease with predominantly cerebellar dysfunction.
Van de Warrenburg et al. (2005) applied statistical analysis to examine the relationship between age at onset and number of expanded triplet repeats from a Dutch-French cohort of 802 patients with SCA1 (138 patients), SCA2 (166 patients), SCA3 (342 patients), SCA6 (53 patients), and SCA7 (103 patients). The size of the expanded repeat explained 66 to 75% of the variance in age at onset for SCA1, SCA2, and SCA7, but less than 50% for SCA3 and SCA6. The relation between age at onset and CAG repeat was similar for all groups except for SCA2, suggesting that the polyglutamine repeat in the ataxin-2 protein exerts its pathologic effect in a different way. A contribution of the nonexpanded allele to age at onset was observed for only SCA1 and SCA6. Van de Warrenburg et al. (2005) acknowledged that their results were purely mathematical, but suggested that they reflected biologic variations among the diseases.
Genotype/Phenotype Correlations
Schols et al. (1997) compared clinical, electrophysiologic, and MRI findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor suggested SCA2. SCA3 (109150) patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome, and patients often had onset after 55 years of age. SCA1 (164400) was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. Overlap among the 4 SCA subtypes was broad, however.
In an investigation of oculomotor function, Buttner et al. (1998) found that all 3 patients with SCA1, all 7 patients with SCA3, and all 5 patients with SCA6 had gaze-evoked nystagmus. Three of 5 patients with SCA2 did not have gaze-evoked nystagmus, perhaps because they could not generate corrective fast components. Rebound nystagmus occurred in all SCA3 patients, 33% of SCA1 patients, 40% of SCA6 patients, and none of SCA2. Spontaneous downbeat nystagmus only occurred in SCA6. Peak saccade velocity was decreased in 100% of patients with SCA2, 1 patient with SCA1, and no patients with SCA3 or SCA6. Saccade hypermetria was found in all types, but was most common in SCA3.
Using an analysis of covariance and multivariate models to examine symptom severity in 526 patients with SCA1, SCA2, SCA3, or SCA6, Schmitz-Hubsch et al. (2008) found that repeat length of the expanded allele, age at onset, and disease duration explained 60.4% of the ataxia score in SCA1, 45.4% in SCA2, 46.8% in SCA3. However, only age at onset and disease duration appeared to explain 33.7% of the score in SCA6. Similar findings were obtained for nonataxic symptoms. The study suggested that SCA1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.
Heterogeneity
In a family initially classified as autosomal dominant cerebellar ataxia of unknown type, Jodice et al. (1997) found an intergenerational allele size change in the CACNA1A gene, showing that a (CAG)20 allele (601011.0008) was associated with the phenotype of episodic ataxia type 2 (EA2; 108500) and a (CAG)25 allele with progressive cerebellar ataxia. These results suggested that EA2 and SCA6 are the same disorder with a high phenotypic variability, at least partly related to the number of repeats, and suggested that the small expansions may not be as stable as previously reported.
Sinke et al. (2001) described a study of 24 Dutch families with SCA6. Clinical analysis identified SCA6 as a late-onset ataxia in which eye movement abnormalities are prominent and consistent early manifestations. Some patients had ataxia combined with episodic headaches or nausea, suggesting an overlap among SCA6, episodic ataxia type 2, and familial hemiplegic migraine (141500).
In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, Alonso et al. (2003) found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; 601011.0018). Four patients, all under the age of 18 years, had only hemiplegic migraine, 8 patients had isolated progressive cerebellar ataxia, and 5 patients had both hemiplegic migraine and cerebellar ataxia. Several patients reported symptoms triggered by minor head trauma. Alonso et al. (2003) suggested that EA2, SCA6, and familial hemiplegic migraine are not only allelic disorders, but may be the same disorder with great phenotypic variability.
Population Genetics
Riess et al. (1997) found that the SCA6 mutation accounts for approximately 10% of autosomal dominant SCA in Germany.
Studying 77 German families with autosomal dominant cerebellar ataxia of SCA types 1, 2, 3, and 6, Schols et al. (1997) found that the SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22%. There was no family history of ataxia in 7 of 27 SCA6 patients. Age at onset correlated inversely with repeat length in all subtypes, yet the average effect of 1 CAG unit on age of onset was different for each SCA subtype. Schols et al. (1998) investigated the SCA6 mutation (expanded repeat in the CACNA1A gene) in 69 German families with autosomal dominant cerebellar ataxia and 61 patients with idiopathic sporadic cerebellar ataxia. The expanded CAG repeat was found in 9 of 69 families, as well as in 4 patients with sporadic disease. Schols et al. (1998) noted that in Germany, SCA6 accounts for about 13% of families with autosomal dominant cerebellar ataxia. However, up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadic disease due to late manifestation in apparently healthy parents. Genetic testing was therefore recommended for the SCA6 mutation also in patients with putative sporadic ataxia. In a study of apparently idiopathic sporadic cerebellar ataxia involving 124 patients, Schols et al. (2000) found the SCA6 mutation in 9 patients with disease onset between 47 and 68 years of age.
Using an intragenic marker, D19S1150, and 2 markers (DS19S221 and DS19S226) bracketing 3 cM on either side, Dichgans et al. (1999) found a common haplotype in 7 of 12 German families segregating SCA6. This finding, as well as a clustering of the families from Northrhine-Westfalia, strongly suggests a founder effect.
From their study of 15 families with autosomal dominant cerebellar ataxia, Ishikawa et al. (1997) concluded that more than half of Japanese cases of ADPCA map to 19p and are strongly associated with a mild CAG expansion in the SCA6/CACNL1A4 gene.
Watanabe et al. (1998) investigated 101 kindreds with spinocerebellar ataxias from the central Honshu island of Japan, using a molecular diagnostic approach with amplification of the CAG trinucleotide repeat of the causative genes. Machado-Joseph disease (109150) was the most prevalent (33.7%) form, followed by dentatorubral-pallidoluysian atrophy (125370; 19.8%), SCA6 (5.9%), and SCA2 (5.9%). All 7 SCA6 patients had expanded alleles of the CACNL1A4 gene and signs of a pure cerebellar syndrome.
Among 202 Japanese and 177 Caucasian families with autosomal dominant SCA, Takano et al. (1998) found that the prevalence of SCA6 was significantly higher in the Japanese population (11%) compared to Caucasian population (5%). This corresponded to higher frequencies of large normal CACNA1A CAG repeat alleles (greater than 13 repeats) in Japanese controls compared to Caucasian controls. The findings suggested that large normal alleles contribute to the generation of expanded alleles that lead to dominant SCA.
Yabe et al. (2001) studied 21 Japanese families with SCA6 and found one of 2 haplotypes in each family. They suggested a mechanism by which the second haplotype could have arisen from a single common haplotype, and that therefore there was evidence of a founder effect in SCA6 families in Japan.
Storey et al. (2000) examined the frequency of mutations for SCA types 1, 2, 3, 6, and 7 in southeastern Australia. Of 63 pedigrees or individuals with positive tests, 30% had SCA1, 15% had SCA2, 22% had SCA3, 30% had SCA6, and 3% had SCA7. Ethnic origin was of importance in determining SCA type: 4 of 9 SCA2 index cases were of Italian origin, and 4 of 14 SCA3 index cases were of Chinese origin.
Sinke et al. (2001) determined that SCA6 accounted for approximately 11% of all Dutch families with autosomal dominant cerebellar ataxia.
Among 74 Taiwanese families with autosomal dominant cerebellar ataxia and 49 Taiwanese patients with sporadic ataxia, Soong et al. (2001) determined that SCA6 accounted for 10.8% of the familial cases and 4.1% of the sporadic cases. The prevalence of SCA3 was 47.3%, followed by SCA2 (10.8%), SCA1 (5.4%), SCA7 (2.7%), and DRPLA (1.4%). In the families with SCA6, there was significant anticipation in the absence of genetic instability. The same allele of intragenic marker D19S1150 was found in 70% of the SCA6 patients, suggesting a founder effect.
Of 253 unrelated Korean patients with progressive cerebellar ataxia, Lee et al. (2003) identified 52 (20.6%) with expanded CAG repeats. The most frequent SCA type was SCA2 (33%), followed by SCA3 (29%), SCA6 (19%), SCA1 (12%), and SCA7 (8%). There were characteristic clinical features, such as hypotonia and optic atrophy for SCA1, hyporeflexia for SCA2, nystagmus, bulging eye, and dystonia for SCA3, and macular degeneration for SCA7.
By haplotype analysis of 12 Dutch SCA6 families confirmed by genotype, Verbeek et al. (2004) found that 8 families (approximately 70%) shared a region between markers D19S1165 and D19S840, including the SCA6 gene, which was not observed in 80 control chromosomes. Two additional SCA6 families shared an extended haplotype. Genealogic research showed that most of the families were clustered in North Holland. The authors noted that mutation in the SCA6 gene occurs in 23.4% of the Dutch autosomal dominant cerebellar ataxia population. Similar haplotype results were found for SCA3.
In a population-based study in Northeastern England, Craig et al. (2004) estimated that the number of people with or at risk for SCA6 was at least 5.21/100,000, or 1 in 19,210. Haplotype analysis suggested a founder effect, and 56% of affected individuals had an identical CAG repeat length (21 repeats). The clinical phenotype of this group was homogeneous.
Shimizu et al. (2004) estimated the prevalence of SCA in the Nagano prefecture of Japan to be at least 22 per 100,000. Thirty-one of 86 families (36%) were positive for SCA disease-causing repeat expansions: SCA6 was the most common form (19%), followed by DRPLA (10%), SCA3 (3%), SCA1 (2%), and SCA2 (1%). The authors noted that the prevalence of SCA3 was lower compared to other regions in Japan, and that the number of genetically undetermined SCA families in Nagano was much higher than in other regions. Nagano is the central district of the main island of Japan, located in a mountainous area surrounded by the Japanese Alps. The restricted geography suggested that founder effects may have contributed to the high frequency of genetically undetermined ADCA families.
Among 113 Japanese families from the island of Hokkaido with autosomal dominant SCA, Basri et al. (2007) found that SCA6 was the most common form of the disorder, identified in 35 (31%) families. Thirty (27%) families had SCA3, 11 (10%) had SCA1, 5 (4%) had SCA2, 5 (4%) had DRPLA, 10 (9%) had 16q22-linked SCA (117210), and 1 (1%) had SCA14 (605361). The specific disorder could not be identified in 16 (14%) families.
Craig et al. (2008) identified a common core haplotype carrying the CACNA1A CAG repeat in 45 SCA6 families from different geographic regions, including Europe, Brazil, and Japan. The haplotype was also present in the unaffected father of a proven de novo Japanese patient, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus. The SCA6 expansion lies immediately downstream of a CpG island, which could act as a cis-acting element predisposing to repeat expansion, as observed for other CAG/CTG repeat diseases.
Animal Model
Watase et al. (2008) found that knockin mice expressing a hyperexpanded polyglutamine (84Q) Cacna1a repeat developed progressive motor impairment consistent with SCA6. Knockin mice with normal 14 CAG or expanded 30 CAG repeats did not show such defects. Electrophysiologic analysis of cerebellar Purkinje cells revealed similar calcium channel current density among the 3 mouse models, although all were decreased compared to wildtype due to decreased channel abundance. Neither voltage sensitivity of activation nor inactivation was altered in the Sca6(84Q) neurons, suggesting that the expanded CAG repeat does not per se affect the intrinsic electrophysiologic properties of the channels. Mice with the hyperexpanded polyglutamine repeat showed cytoplasmic neuronal inclusions, consistent with aggregation of mutant calcium channels. Watase et al. (2008) concluded that the pathogenesis of SCA6 is related to an age-dependent process accompanied by accumulation of mutant CACNA1A channels resulting in a toxic gain-of-function effect.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Gaze-evoked nystagmus \- Impaired smooth pursuit \- Abnormal vestibuloocular reflex (VOR) NEUROLOGIC Central Nervous System \- Cerebellar ataxia \- Dysarthria \- Dysphagia \- Cerebellar atrophy \- Hemiplegic migraine in some patients \- Selective loss of cerebellar Purkinje cells Peripheral Nervous System \- Sensory neuropathy (not a prominent feature) MISCELLANEOUS \- Age of onset 20-65 years \- Progressive disorder \- Normal alleles have 4 to 18 repeats \- Pathogenic alleles have 19 to 33 repeats \- Genetic anticipation MOLECULAR BASIS \- Caused by expanded CAG trinucleotide repeats in the alpha-1A calcium channel subunit gene (CACNA1A, 601011.0007 ) \- Caused by mutation in the alpha-1A calcium channel subunit gene (CACNA1A, 601011.0002 ) ▲ 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
|
SPINOCEREBELLAR ATAXIA 6
|
c0752124
| 8,239 |
omim
|
https://www.omim.org/entry/183086
| 2019-09-22T16:34:31 |
{"doid": ["0050956"], "mesh": ["D020754"], "omim": ["183086"], "orphanet": ["98758"], "genereviews": ["NBK1140"]}
|
Non-immune hydrops fetalis (NIHF), a form of HF, is a severe fetal condition defined as the excessive accumulation of fetal fluid within the fetal extravascular compartments and body cavities, and is the end-stage of a wide variety of disorders.
## Epidemiology
The prevalence of NIHF is unknown as it is difficult to obtain when many cases are not diagnosed before intrauterine death or may spontaneously resolve antenatally. Currently, NIHF constitutes up to 90% of all HF cases.
## Clinical description
NIHF presents during the gestational period and manifests as pleural and pericardial effusion, ascites and subcutaneous edema in the fetus. Decreased fetal movements may be noted prior to diagnosis. Often associated are polyhydramnios, fetal tachycardia, and antenatal hemorrhage. Mothers may develop massive anasarca, hypertension, and proteinuria (mirror syndrome). Death of fetus is usually due to heart failure and hypoxia. Surviving newborns may present with respiratory distress, pale skin, severe edema (mainly of abdomen) and enlarged liver and spleen. There is sometimes a risk of death of the mother.
## Etiology
NIHF is the result of an increase in interstitial fluid production or, in turn, of an obstruction of lymphatic return. Causes can be: cardiovascular (21.7%; Ebstein malformation, tetralogy of Fallot), hematologic (10.4%; Hb Bart's HF), chromosomal (13.4%; Turner syndrome) and more rarely: infectious (TORCHES-CLAP (Toxoplasma gondii; Rubella virus; Cytomegalovirus; Herpes simplex virus; Enterovirus; Syphilis; Chickenpox virus; Lyme disease; Aids; Parvovirus B19)), syndromic (Costello syndrome, Meckel syndrome, thanatophoric dysplasia) or idiopathic. Other causes can include lymphatic dysplasia, inborn errors of metabolism (transaldolase deficiency, mucopolysaccharidosis, Niemann-Pick disease type C, GM1 gangliosidosis type 1), thoracic and urinary tract malformations, cardiac /extra thoracic tumors, and congenital diaphragmatic hernia.
## Diagnostic methods
Decreased fetal movements, polyhydramnios, and maternal pre-eclampsia may lead one to suspect NIHF. Diagnosis is usually by ultrasound (showing fluid accumulations) during the 2nd to 3rd trimester of gestation. Having a placenta thickness of 5 mm or more, especially with a ''ground glass'' appearance on ultrasound may also be indicative of NIHF. Maternal laboratory tests such as blood typing, antibody screens for TORCHES-CLAP, hemoglobin electrophoresis, maternal anti-SSA/SSB antibodies as well as Kleihauer-Betke and alpha-fetoprotein tests, can also aid in the diagnosis of NIHF.
## Differential diagnosis
The many disorders associated with HF are differential diagnoses such as neonatal hemochromatosis, twin-to-twin transfusion syndrome, congestive heart failure, hepatitis B, hypercalcemia, hypernatremia, hypothrombinemia, hypothyroidism and diabetes (in mother). Conditions that mimic full-blown HF include obstructed or mature bowel, fetal abdominal cysts and an obstructed urinary system.
## Antenatal diagnosis
Prenatal diagnosis is by ultrasound.
## Genetic counseling
If NIHF is due to a genetic disorder, counseling can be offered in regards to that disease.
## Management and treatment
Treatment depends on the cause. Intrauterine treatment can involve thoraco-amniotic drainage, antiarrhythmic drugs (digoxin, sotalol, propranolol) and blood transfusion when anemia is present. In many cases, especially those caused by chromosomal abnormalities, the mother may choose to terminate the pregnancy. If the fetus comes to term it should be delivered at a tertiary care center where the neonate can receive intensive resuscitation procedures in the delivery room, intensive neonatal care, high frequency ventilation, parenteral nutrition, medications for the kidneys and removal of excessive fluid from around the lungs and abdomen as necessary.
## Prognosis
In most cases, prognosis is poor with a perinatal mortality rate ranging from 55-98%, but it is dependent on etiology.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Non-immune hydrops fetalis
|
c0455988
| 8,240 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363999
| 2021-01-23T17:57:19 |
{"mesh": ["D015160"], "omim": ["236750"], "umls": ["C0455988"], "icd-10": ["P56.9", "P83.2"], "synonyms": ["NIHF", "Non-immune HF", "Non-immune fetal edema", "Non-immune fetal hydrops"]}
|
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Oedema glottidis
SpecialtyOtolaryngologist
Oedema glottidis is defined as the abnormal accumulation of fluid in tissues involving the supraglottic and subglottic region where laryngeal mucosa is loose. It is also known as Laryngeal Oedema.[1]
## References[edit]
1. ^ PL Dhingra, Shruti Dhingra and Deeksha Dhingra. 2016. Diseases of Ent, Nose and Throat & Head and neck Surgery. 6th ed. Elsevier, a division of Reed Elsiever India Private Limited
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Oedema glottidis
|
c0023052
| 8,241 |
wikipedia
|
https://en.wikipedia.org/wiki/Oedema_glottidis
| 2021-01-18T18:48:04 |
{"mesh": ["D007819"], "umls": ["C0023052"], "wikidata": ["Q1806419"]}
|
## Clinical Features
Guo et al. (2006) reported a large 4-generation Chinese family with 6 males affected by congenital cataracts, cerebellar ataxia, short stature, and mental retardation and with 8 females affected by cataracts alone. The 4 affected males who were examined had total opacification of the lens but normal cornea, anterior chamber, and iris; they were much shorter than their unaffected sibs or parents. Neurologic evaluation revealed mild to moderate mental retardation, muscle hypotonia and weakness, dysarthria, and postural tremor. Their stances were broad based, and they were unable to sit or stand without support. Affected females reported blurred vision starting in childhood or teenage years. Examination revealed either cortical punctate or pulverulent opacities and posterior subcapsular opacities of the lens, with normal cornea, anterior chamber, iris, and pupils; the fundus, when visible, was normal. All affected females had normal stature and normal psychomotor development. The pedigree was consistent with an X-linked trait partially penetrant in female carriers.
Mapping
In a large 4-generation Chinese family with 6 males affected by congenital cataracts, cerebellar ataxia, short stature, and mental retardation and 8 females affected by cataract alone, Guo et al. (2006) performed a complete scan of the X chromosome and found linkage to Xpter-q13.1, with a maximum lod score of 3.91 for DXS1226, DXS991, and DXS1213 (theta = 0.0). Linkage analysis mapped cataract to Xpter-q13.1 as well, with the highest lod score of 6.32 at DXS1226 (theta = 0.0). Haplotype analysis revealed that the disease allele cosegregated with all female carriers as well as affected males in an X-linked recessive fashion.
INHERITANCE \- X-linked recessive GROWTH Height \- Short stature HEAD & NECK Eyes \- Cataract, complete (in affected males) \- Cortical punctate or pulverulent opacities (in carrier females) \- Posterior subcapsular opacities of the lens (in carrier females) MUSCLE, SOFT TISSUES \- Muscle weakness NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Cerebellar ataxia \- Dysarthria \- Postural tremor \- Hypotonia ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CATARACT, ATAXIA, SHORT STATURE, AND MENTAL RETARDATION
|
c1845094
| 8,242 |
omim
|
https://www.omim.org/entry/300619
| 2019-09-22T16:20:00 |
{"mesh": ["C535345"], "omim": ["300619"], "synonyms": ["Alternative titles", "CASM SYNDROME"]}
|
## Summary
### Clinical characteristics.
Incontinentia pigmenti (IP) is a disorder that affects the skin, hair, teeth, nails, eyes, and central nervous system; it occurs primarily in females and on occasion in males. Characteristic skin lesions evolve through four stages:
I.
Blistering (birth to age ~4 months)
II.
Wart-like rash (for several months)
III.
Swirling macular hyperpigmentation (age ~6 months into adulthood)
IV.
Linear hypopigmentation
Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Neovascularization of the retina, present in some individuals, predisposes to retinal detachment. Neurologic findings including seizures, intellectual disability, and developmental delays are occasionally seen.
### Diagnosis/testing.
The diagnosis of IP is established in a proband with at least one major criterion (characteristic skin lesion). Identification of a heterozygous IKBKG pathogenic variant in a female proband or a hemizygous IKBKG pathogenic variant in a male proband confirms the diagnosis if clinical features are inconclusive.
### Management.
Treatment of manifestations: Standard management of blisters and skin infections; dental care by a pedodontist; dental implants in childhood as needed; care by a speech pathologist and/or pediatric nutritionist if dental abnormalities interfere with chewing and/or speech; cryotherapy and laser photocoagulation of retinal neovascularization to reduce risk of retinal detachment; standard management of retinal detachment; referral to a pediatric neurologist for management of seizures, spasticity, or focal deficits; brain MRI for functional neurologic abnormalities and/or retinal neovascularization; developmental programs and special education as needed for developmental delay.
Prevention of secondary complications: Standard measures to reduce the risk of skin infection; evaluate for retinal detachment if vision decreases, strabismus appears, or head trauma occurs.
Surveillance: Eye examination: monthly until age four months, then every three months from age four months to one year, every six months from age one to three years, and annually after age three years. Assessment of neurologic function at routine visits with pediatrician, pediatric neurologist, or developmental pediatrician; routine evaluation by a pedodontist or dentist.
Evaluation of relatives at risk: Identification of affected relatives by physical examination and retinal examination so that screening ophthalmology examinations can be performed.
### Genetic counseling.
IP is inherited in an X-linked manner. About 65% of affected individuals have IP as a result of a de novo pathogenic variant. Heterozygous, affected women have a 50% chance of transmitting the IKBKG pathogenic variant at conception; however, male conceptuses with an IKBKG loss-of-function variant miscarry. Thus, the expected ratio among liveborn children of a mother with IP is approximately 33% unaffected females, 33% affected females, and 33% unaffected males. To date, all males with IP have had either a 47,XXY karyotype or somatic mosaicism for the IKBKG pathogenic variant. A male with somatic and germline mosaicism may transmit the IKBKG pathogenic variant to daughters (females who inherit the pathogenic variant will be affected); an affected male would not transmit an IKBKG pathogenic variant to sons. Prenatal testing for pregnancies at increased risk and preimplantation genetic testing are possible if the familial pathogenic variant has been identified.
## Diagnosis
### Suggestive Findings
Incontinentia pigmenti (IP) should be suspected in individuals with characteristic clinical findings of the skin, teeth, hair, nails, eyes, and CNS, and family history as detailed below.
Major criteria (skin lesions that occur in stages from infancy to adulthood)
* Erythema followed by blisters (vesicles) anywhere on the body except the face, usually in a linear distribution. The blisters clear within weeks and may be replaced by a new crop. Erythema occurs in stage I (first weeks of life to age 24 months; most prominent before age 6 months)
* Verrucous lesions that respect Blaschko's lines, occurring mainly on the limbs; stage II (first weeks of life to 24 months)
* Hyperpigmented streaks and whorls that respect Blaschko's lines, occurring mainly on the trunk and fading in adolescence; stage III (age 4 months to 16 years, rarely persisting into adulthood)
* Pale, hairless, atrophic linear streaks or patches; stage IV (adolescence through adulthood)
Note: Though the lesions classically occur in the indicated stages, more than one type of lesion may be present at any time. The locations of the lesions can vary from stage to stage.
Minor criteria
* Teeth. Hypodontia or anodontia (partial or complete absence of teeth), microdontia (small teeth), abnormally shaped teeth
* Hair. Alopecia, woolly hair (lusterless, wiry, coarse)
* Nails. Mild ridging or pitting; onychogryposis (hypertrophied, curved nails)
* Retina. Peripheral neovascularization
* Family history consistent with X-linked inheritance or a history of multiple miscarriages
Note: (1) The presence of minor criteria supports the clinical diagnosis. (2) Minić et al [2014] have suggested that CNS, palate, and nipple/breast anomalies be added to the minor diagnostic criteria.
### Establishing the Diagnosis
The diagnosis of IP is established in a proband if at least one of the major criteria is present. If clinical features are inconclusive, the diagnosis of IP can be established by identification on molecular genetic testing of one of the following:
* A heterozygous IKBKG pathogenic variant in a female proband
* A hemizygous IKBKG pathogenic variant in a male proband
* Mosaicism for an IKBKG pathogenic variant in a male proband (see Table 1)
The most efficacious molecular genetic testing approach is single-gene testing.
Single-gene testing. Targeted analysis for the common 11.7-kb IKBKG deletion can be performed first or concurrently with sequence analysis of IKBKG followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found.
Note: Analysis of IKBKG is complicated by the presence of a highly homologous pseudogene, IKBKGP1. For more information on pseudogenes, click here.
Note: In affected males, somatic mosaicism can result in failure to detect an IKBKG loss-of-function pathogenic variant. For this reason, molecular genetic testing of a tissue sample (e.g., skin from an affected site, sperm), may be needed if no pathogenic variant is identified by molecular genetic testing of a blood sample.
A multigene panel that includes IKBKG and other genes of interest (see Differential Diagnosis) may be considered. Note: (1) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. In the case of IKGKG, sequencing methods other than NGS must be employed due to the presence of IKBKGP1. (2) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (3) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (4) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (5) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 1.
Molecular Genetic Testing Used in IP
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
FemalesMales
IKBKGTargeted analysis for ~11.7-kb common deletion (c.399-?_1260+?del)~65% 33/18 (16%) 4
Sequence analysis 5, 6~8.6% 42 individuals 7
Gene-targeted deletion/duplication analysis 8~4% 9None reported
Unknown 10NA
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Fusco et al [2008]
4\.
Three of 18 males with IP with somatic mosaicism for the common 11.7kb deletion [Fusco et al 2007]
5\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
6\.
Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
7\.
Fusco et al [2017] reported a male with IP with somatic mosaicism for the c.394C>T pathogenic variant. Chang et al [2008] reported a male with the pathogenic variant c.1167dupC (also known as 1167insC); he is the only male known to have both HED-ID (hypohidrotic ectodermal dysplasia and immunodeficiency) and the skin findings of IP (see Genetically Related Disorders).
8\.
Gene-targeted deletion/duplication analysis detects locus-specific deletions or duplications. Methods used may include quantitative PCR, long-range PCR, and Southern blotting. Assay designs must account for presence of the IKBKG pseudogene.
9\.
Quantitative PCR analysis of IKBKG locus to evaluate partial copy number loss or copy number gain along the locus revealed pathogenic variants due to aberrant recombination in the locus producing deletions involving IKBKG, the IKBKG pseudogene, and eventually the neighboring gene G6PD [Fusco et al 2012, Conte et al 2014].
10\.
Although no evidence of additional loci causing IP has been reported, there remain 4.7% of individuals with IP who have no pathogenic variant in the IKBKG locus assigned. For them locus heterogeneity cannot be excluded [Fusco et al 2014].
Skin biopsy for histopathology can be considered in affected individuals in whom an IKBKG pathogenic variant is not identified on molecular genetic testing.
* Affected females. Identification of eosinophilic infiltration and/or extracellular melanin granules on histologic examination of a skin biopsy can suggest or confirm the diagnosis in females with characteristic clinical features, but is now rarely needed given the widespread availability and sensitivity of molecular genetic testing (see Table 1). Nonetheless, skin biopsy may be helpful in confirming the diagnosis in a female with borderline or questionable findings in whom molecular genetic testing has not identified a pathogenic variant.
* Affected males. Histologic examination of skin biopsy may be more helpful in males, particularly when mosaicism is being considered. Routine pathologic examination may be done on the same biopsy used for molecular genetic testing.
## Clinical Characteristics
### Clinical Description
Incontinentia pigmenti (IP) is a disorder of the skin and its appendages, eye, and central nervous system (CNS) that occurs primarily in females and on occasion in males.
The largest cohort of individuals with IP in whom the clinical and molecular diagnosis has been confirmed is reported in Fusco et al [2014].
Skin. See Figure 1, Figure 2, Figure 3, and Figure 4. IP manifests in stages that evolve sequentially. The onset and duration of each stage vary among individuals, and not all individuals experience all four stages. The skin abnormalities that define each stage occur along lines of embryonic and fetal skin development known as Blaschko's lines (see Figure 3). Blaschko's lines correspond with cell migration or growth pathways that are established during embryogenesis. Like dermatomes, they are linear on the limbs and circumferential on the trunk. Unlike dermatomes, Blaschko's lines do not correspond to innervation patterns or spinal cord levels.
#### Figure 1.
IP in an affected female; stage I: the blistering stage. Note that the blisters are not necessarily linear.
#### Figure 2.
IP in an affected female; stage II: the verrucous ("warty") stage. The lesions do not necessarily arise in the same place as those of stage I.
#### Figure 3.
IP in an affected female with stage III "rash"
#### Figure 4.
An adult with reticulated pigmentation patterns
* Stage I – The bullous stage is characterized by blister-like bullous eruptions (Figure 1) that are linear on the extremities and/or circumferential on the trunk. The eruptions can be erythematous and may appear infectious. Stage I manifests within the first six to eight weeks and can be present at birth. The stage I rash generally disappears by age 18 months, although a vesicobullous eruption was reported in a girl age five years who was already manifesting the stage IV rash [Darné & Carmichael 2007].
* Stage II – The verrucous stage is characterized by a hypertrophic, wart-like rash that is linear on the extremities and/or circumferential on the trunk (see Figure 2). This stage manifests within the first few months of life. It can occasionally be present at birth but typically arises as stage I begins to resolve. Stage II usually lasts for a few months, but it can last for years. Stage II can also include the appearance of dystrophic nails and abnormalities of tooth eruption.
* Stage III – The hyperpigmentation stage is characterized by macular, slate gray, or brown hyperpigmentation that occurs in a "marble cake" or swirled pattern along Blaschko's lines, usually circumferential on the trunk and linear on the extremities (see Figure 3). The hyperpigmentation stage is the most characteristic stage for IP. Not all women have extensive hyperpigmentation; it can be quite limited. The most frequently involved areas are the groin and axilla. The entire skin surface may need to be examined to find characteristic patterns. Hyperpigmentation begins between age six months and one year, usually as stage II begins to resolve. It is NOT present at birth. Stage III can persist into adulthood. The hyperpigmentation usually begins to fade in the teens and early twenties (see Figure 4). The pigmentation changes can be linear, swirled, or reticulated. A woman in her thirties or later may show no skin changes associated with IP.
* Stage IV – The atretic stage is characterized by linear hypopigmentation and alopecia, particularly noticeable on the extremities and, when it happens, on the scalp. The definition of stage IV remains open. There may not be true hypopigmentation, but rather a loss of hair and epidermal glands. As with the first three stages, the pattern follows Blaschko's lines. Stage IV does not occur in all individuals. When present, it arises after the hyperpigmentation fades.
Hair. Alopecia may occur on the scalp and also on the trunk and extremities. Patchy alopecia of the scalp may correspond to areas of scarring left from blistering in stage I, but may also occur in individuals who have had no stage I or II lesions on the scalp. Alopecia occurs in areas of skin hypopigmentation as part of stage IV skin changes. Scalp hair may be thin or sparse in early childhood. Hair may also be lusterless, wiry, and coarse, often at the vertex in a "woolly-hair nevus." Areas of alopecia may be very small, unnoticed by the affected individual and difficult to find, particularly when covered by other scalp hair. Sparse eyelashes and eyebrows are also reported.
Teeth. Abnormalities include hypodontia (too few teeth), microdontia (small teeth), abnormally shaped teeth (e.g., conical teeth or accessory cusps), delayed eruption, or impaction. Enamel and tooth strength are normal. The tooth anomalies reported in individuals with IP are widely variable and may be said to encompass virtually any aberration in tooth shape and/or number.
Nails. Nails can be dystrophic (i.e., lined, pitted, or brittle). These changes often resemble fungal infections of the nails. Dystrophic nails are most commonly associated with stage II. The nail changes may be transient, but a single, chronic, longitudinal ridge in the nail was present in 28% of persons in one study [Phan et al 2005].
Ophthalmologic. Individuals with IP are at increased risk (20%-77%) for ophthalmologic abnormalities.
* Retinal hypervascularization is most common. When untreated, this leads to retinal detachment. The greatest risk for retinal detachment is in infancy and childhood; it almost never occurs after age six years. The changes are visible on indirect ophthalmoscopy through a dilated pupil.
* Other eye findings include strabismus, cataracts, optic atrophy, retinal pigmentary abnormalities, and microphthalmia [Meuwissen & Mancini 2012, Fusco et al 2014].
Central nervous system. Seizures, intellectual disability, and other CNS abnormalities have been reported in approximately 30% of individuals with IP [Minić et al 2014]. The actual incidence of neurocognitive disability is unclear because mildly affected individuals without neurocognitive problems may not come to medical attention [Phan et al 2005]. Neurocognitive disability is more common in simplex than in familial cases, presumably because mildly affected family members are identified. Males with IP are more likely than females to have neurologic abnormalities. In general, neurologic abnormalities in individuals with IP appear to be associated with underlying CNS vasculopathy [Meuwissen & Mancini 2012].
* Seizures. Seizures in IP range from a single episode in a lifetime to chronic epilepsy. The type of seizure varies because the stroke etiology may involve any part of the cerebrum. In the review of well-documented individuals with IP who have neurocognitive disability, Meuwissen & Mancini [2012] note that of seizure types reported, focal clonic seizures were the most frequently observed. Of all affected persons with neurocognitive problems, about 25% experience one or more seizures (i.e., ~7% of all individuals diagnosed with IP). The vast majority of seizures manifest within the first year of life (32 of 35 individuals with seizures where onset was reported). Fourteen of 25 individuals in whom recurrence was reported experienced only one seizure [Meuwissen & Mancini 2012].
* Intellect. Available studies of cognitive function in IP are limited. There is a range of function, including normal. Severe intellectual disability is not common. In males, co-occurrence of a 47,XXY karyotype may complicate the intellectual phenotype of IP.
Pizzamiglio et al [2014] reported a group of ten females with IP who were underwent cognitive assessment. Seven of the ten had deficits in calculation/arithmetic reasoning and reading but not writing skills. This evaluation makes it possible to place "learning disabilities" among the manifestations of IP. A follow-up study in 2017 [Pizzamiglio et al 2017] showed that nine of 14 girls had normal development while five had intellectual disabilities ranging from mild to severe.
* Brain anomaly. Primary brain anomalies are rare. The following have each been reported in separate affected individuals: agenesis of the corpus callosum with an occipital encephalocele [Demirel et al 2009]; polymicrogyria [Godambe et al 2005]; and gray matter heterotopias [Mangano & Barbagallo 1993].
Evidence that IKBKG pathogenic variants may cause abnormalities in microvasculature supports the theory that CNS dysfunction is secondary to vascular problems that result in transient ischemic attacks or full-blown hemorrhagic strokes [Fiorillo et al 2003, Hennel et al 2003, Shah et al 2003]. Neurovascular abnormalities are most common in the first year of life, with only a handful of individuals reported after that, and only three after age four years [Meuwissen & Mancini 2012].
Periventricular leukomalacia was identified on brain MRI in 27 of 43 individuals with IP who have neurocognitive disabilities, especially seizures, and subcortical white matter changes were also seen commonly. Some individuals have subsequent cystic changes. Myelination delays and ventricular dilation have also been reported [Meuwissen & Mancini 2012].
* Spastic paresis. The frequency of this finding is unknown. It is difficult to interpret older literature findings. As with other neurologic abnormalities in IP, the risk and severity of spastic paresis appears to be related to CNS vasculopathy.
Breast. Abnormalities of mammary tissue ranging from aplasia of the breast to supernumerary nipples are variably present but are more common than in the general population [Minić et al 2014]. The recognized frequency of breast abnormalities may be limited because reports tend to focus on prepubertal children.
Other
* Leukocytosis with up to 65% eosinophils may occur, particularly in stages I and II. The specific cause of the leukocytosis is unknown. Zilberman-Rudenko et al [2016] note that pathogenic variants in IKBKG impair suppression of NF-KB, leading to hyperactive reactive inflammatory response. Eosinophilia is not consistently associated with any clinical manifestations and typically resolves spontaneously.
* Primary pulmonary hypertension has been reported in some individuals and is presumably related to vasculopathy [Alshenqiti et al 2017].
Males with IP. Although IP has been identified as a "male-lethal" disease, there are well-documented affected males. There are a few individual case reports published each year and intermittent reviews of the literature.
Survival in a male is mediated through one of two mechanisms:
* 47,XXY karyotype, estimated to be present in 7% of males with IP [Pacheco et al 2006]
* Somatic mosaicism
* Low-level mosaicism of 46,XY/47,XXY was demonstrated in one male only by interphase FISH using X and Y probes [Franco et al 2006]. The affected child did not have a demonstrable IKBKG pathogenic variant.
* Low-level mosaicism for an IKBKG loss-of-function pathogenic variant was identified in two males; fibroblast and sperm DNA contained the highest percentage of abnormal cells [Fusco et al 2017].
* Some males also exhibit "segmental" IP (lesions restricted to a single limb), a finding consistent with somatic mosaicism.
The reasoning behind male lethality in IP is that male conceptuses that inherit an X chromosome with a mutated IKBKG gene lack the normal protein necessary for viability. The precise mechanism of male lethality is unknown [Hatchwell 1996], although mouse models suggest that liver failure plays a role [Rudolph et al 2000].
Pathogenic variants that produce a milder form of the condition are always associated with immunodeficiency, known as X-linked hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID), in males [Fusco et al 2008]. Only one male has been reported with HED-ID and also clinical findings of IP in association with the c.1167dupC IKBKG variant [Chang et al 2008].
Life expectancy. For persons without significant neonatal or infantile complications, life expectancy is considered to be normal.
Reproductive fitness. Women with IP are at increased risk for pregnancy loss, presumably related to low viability of male fetuses. It is common for women with IP to experience multiple miscarriages, often around the third or fourth month of gestation. Fertility does not otherwise appear to be impaired; conception of an unaffected fetus would be expected to result in an uncomplicated pregnancy and delivery.
### Genotype-Phenotype Correlations
A group of pathogenic variants (mainly located in exon 10) that result in impaired but not absent NF-kappaB signaling [Fusco et al 2008] are associated with a milder IP phenotype in females and a lower risk of miscarriage of male fetuses. Additionally, most of these variants (which include missense, single base insertion/deletion causing frameshift, and nonsense variants) allow survival of males with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema (OLEDAID) (see Genetically Related Disorders).
### Penetrance
Incontinentia pigmenti has high penetrance. Most persons with IP appear to express the phenotype within a few months after birth.
Expressivity, however, is highly variable. In addition, the skin findings can resolve over time and may be indistinguishable from other skin conditions with age. Furthermore, the dental, hair, and nail abnormalities can be managed cosmetically such that an affected adult woman may not have clinically evident diagnostic findings on physical examination.
### Nomenclature
Some individuals with structural abnormalities of the X chromosome manifest swirled hyperpigmentation even though their X-chromosome abnormalities do not involve the IKBKG locus (Xq28). This observation led to the designation of a separate condition, incontinentia pigmenti type I (IP type I), with a suggested locus at Xp11. Detailed research failed to document consistent linkage to Xp11 or a consistent phenotype. Thus, the designation "IP type I" is thought to be incorrect [Happle 1998].
### Prevalence
More than 2,000 females with IP have been reported [Minić et al 2014]. The number of reported females and males continues to grow, especially with further delineation of the underlying molecular mechanisms. Public health birth defect surveillance systems put the birth prevalence of IP at 0.6–0.7/1,000,000 [Orphanet, Texas Birth Defects Registry, Unpublished data]. The female:male ratio is 20:1 [Orphanet Report Series 2017]. Orphanet recently estimated prevalence at birth of 1.2/100,000 in the European Union.
## Differential Diagnosis
A diagnosis other than incontinentia pigmenti (IP) should be considered when an individual has skeletal involvement (other than secondary to neurologic deficit), gross neurologic deficit, severe alopecia, atypical hyperpigmentation, or gross hypopigmentation. Body segment asymmetry is not usually associated with IP; however, one individual with IP and transverse terminal upper acromelia has been reported [Hayes et al 2005].
The differential diagnosis for the skin manifestations of IP varies by stage. Because a child with IP may have an infectious comorbidity, findings consistent with an infectious disease should be evaluated accordingly, regardless of the presence of IP.
* Stage I – blistering stage. The following need to be considered: congenital herpes simplex, varicella, staphylococcal or streptococcal bullous impetigo, and (in severe cases) epidermolysis bullosa (see Dystrophic Epidermolysis Bullosa, Epidermolysis Bullosa Simplex). The infectious conditions are typically associated with other signs of inflammation including fever and symptoms of systemic toxicity. Scrapings and cultures of the lesions are diagnostic for the infectious diseases. Blistering lesions that appear after light trauma are characteristic of epidermolysis bullosa. Diagnosis is established by analysis of a skin biopsy, transmission electron microscopy or immunofluorescent antibody/antigen mapping, and molecular genetic testing.
* Stage II – verrucous stage. The findings are not likely to be confused with other conditions, although an individual with mild IP may have skin findings that resemble simple warts or molluscum contagiosum. When the lesions are numerous and appear in the appropriate pattern, they are more likely to be IP than either warts or molluscum contagiosum. Differentiating single IP lesions from warts can be difficult without a biopsy.
* Stage III – hyperpigmented stage. The differential diagnosis includes any condition that leads to irregular areas of skin pigmentation or other anomalies along the lines of Blaschko.
Linear and whorled pigmentation changes are a frequent finding in mosaic chromosome abnormalities. Individuals with chromosomal mosaicism often have intellectual disability and congenital malformations, including brain anomalies and the pigmentation abnormalities are present from birth without preceding rashes. Routine karyotyping on blood and/or skin (fibroblast) sample should be considered in these individuals. Hypomelanosis of Ito (OMIM 300337) is a phenotype related to chromosomal mosaicism. Another important differentiation is that in individuals with IP the hyperpigmented areas are abnormal, whereas in hypomelanosis of Ito hypopigmentated areas are abnormal. In individuals with chromosomal mosaicism, it can often be difficult to distinguish which pigmentation level is the "normal" for the individual.
* Stage IV – atretic stage. The atretic skin areas can resemble scarring, vitiligo (with localized alopecia), or any other condition demonstrating hypopigmentation and localized alopecia. Differentiation is based largely on medical history. Vitiligo is progressive and the hypopigmented areas can be surrounded by areas of hyperpigmentation. Vitiligo is not preceded by the other stages of IP or accompanied by non-cutaneous manifestations. Piebaldism (OMIM 172800), an autosomal dominant form of hypopigmentation in which manifestations are limited to the skin, is most often present at birth and does not progress.
The differential diagnosis of other manifestations of IP includes the following disorders:
* Naegeli syndrome (OMIM 161000), a rare autosomal dominant disorder affecting the skin and skin derivatives, resembles IP, but also includes hyperhidrosis and punctate hyperkeratosis of the palms and soles. Unlike IP, Naegeli syndrome does not evolve through different stages of skin involvement. Naegeli syndrome is extremely rare; an individual with linear, wart-like lesions is more likely to have IP. Pathogenic variants in KRT14 cause Naegeli syndrome.
* Retinal neovascularization is observed in retinopathy of prematurity and familial exudative vitreoretinopathy, which can be inherited in an X-linked recessive manner as part of the Norrie disease spectrum (see OMIM 310600) or in an autosomal dominant manner (see Phenotypic Series: Exudative vitreoretinopathy). Skin findings are not present in these disorders.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with incontinentia pigmenti (IP), the following evaluations are recommended if they have not already been completed:
* Physical examination with particular emphasis on the skin, hair, nails, and neurologic system to establish the presence and extent of manifestations
* Consultation with a clinical geneticist and/or genetic counselor
* Involvement of a pediatric dermatologist for management of individuals with significant skin involvement
* Prompt examination by an ophthalmologist familiar with IP and/or diseases of the retina for evidence of retinal neovascularization
* Brain MRI examination and referral to a neurologist for an EEG if seizures, other neurologic abnormalities, or retinal hypervascularization are present
* Magnetic resonance angiography, potentially useful in identifying cerebrovascular lesions if the neurologic deficit is consistent with a stroke-like pattern
* Developmental evaluation if significant delays are identified
* Involvement of a pediatric cardiologist for management of neonates with pulmonary hypertension
### Treatment of Manifestations
Treatment includes the following:
* Management of blisters in a standard manner (i.e., not opening them, avoiding trauma); topical treatment (e.g., medications, oatmeal baths) to relieve discomfort. Significant skin involvement may benefit from dermatology management.
* Treatment of infections as for any other cellulitis
* Referral to a pedodontist at age six months or when teeth erupt, whichever comes first. Dental implants have been performed as early as age seven years (as in children with ectodermal dysplasia, who have similar dental problems (see Hypohidrotic Ectodermal Dysplasia).
* Referral to a speech pathologist and/or pediatric nutritionist if delayed or inadequate eruption of primary teeth interferes with chewing and/or speech development
* For retinal neovascularization that predisposes to retinal detachment, cryotherapy and laser photocoagulation
* Standard treatment for retinal detachment
* Referral to a pediatric neurologist for treatment of seizures and if spasticity, focal deficits, or retinal hypervascularization are present
* Brain MRI in any child with functional neurologic abnormalities or retinal neovascularization
* Appropriate developmental stimulation and special education as indicated for developmental delay
* Standard management of neonatal pulmonary hypertension
### Prevention of Secondary Complications
Management in the newborn period is aimed at reducing the risk of infection of blisters using standard medical management: not rupturing sealed blisters, keeping the areas clean while they are healing, and careful monitoring for excessive inflammation and signs of systemic involvement.
The parents should be instructed about the possibility of retinal detachment particularly in children younger than age seven years; any apparent changes in vision or any evidence of acquired strabismus should be evaluated promptly. Head trauma may precipitate retinal detachment; therefore, any evaluation for head trauma should include a thorough eye examination. There is currently no specific recommendation for avoidance of contact sports.
### Surveillance
No schedule for eye examinations has been established, but the following has been suggested:
* Monthly until age three to four months
* Every three months between ages four months and one year
* Every six months between ages one and three years
* Annually after age three years
Neurologic function should be assessed at routine visits with a pediatrician, pediatric neurologist, or developmental pediatrician.
Ongoing evaluation by a pedodontist or dentist is appropriate.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures (routine eye examinations).
Evaluations can include:
* Molecular genetic testing if the pathogenic variant in the family is known;
* Physical examination including examination of the skin, teeth, hair, nails, retina, and neurologic assessment if the pathogenic variant in the family is not known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Overall pregnancy health and management usually does not vary from normal. The risk of spontaneous abortion related to fetal viability is higher than population rates, but management of pregnancy loss is done in the standard manner. For women with retinal problems, delivery management to minimize or eliminate labor should be considered to avoid retinal detachment.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Incontinentia Pigmenti
|
c0021171
| 8,243 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1472/
| 2021-01-18T21:17:54 |
{"mesh": ["D007184"], "synonyms": ["Bloch-Sulzberger Syndrome"]}
|
A number sign (#) is used with this entry because of evidence that variation in episodic and/or working memory is associated with heterozygous variants in the KIBRA gene (WWC1; 610533) on chromosome 5q34.
Inheritance
The heritability of memory performance is about 50% (McClearn et al., 1997).
Molecular Genetics
Papassotiropoulos et al. (2006) performed a genomewide screen to identify memory-related gene variants and identified a genomic locus encoding the brain protein KIBRA that was significantly associated with memory performance in 3 independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures, including hippocampus and temporal lobe. In mice, in situ hybridization showed that Kibra expression is highest in the dentate gyrus and the Ca1 region of hippocampal formation, 2 key regions for memory. FMRI detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Papassotiropoulos et al. (2006) found that carriers of the KIBRA rs1707145 T allele (see 610533.0001) had a 24% better free recall performance 5 minutes after word presentation (p = 0.000004) and 19% better free recall performance 24 hours after word presentation (p = 0.0008) than did noncarriers.
Schaper et al. (2008) studied cognition in aging in 64 carefully phenotyped, cognitively healthy participants. All subjects were free of memory complaints and showed intact cognitive performance by scoring within 1.5 standard deviations of the German age-, gender-, and education-adjusted range on the CERAD neuropsychologic battery. None was suffering from any psychiatric, neurologic, or significant medical disorder and none was taking medication with known effect on cognition. Thirty-five participants were carriers of the rs17070145 CT (33) or TT (2) genotype (23 males, 12 females; mean age, 67.1 +/- 7.3; years of formal education, 15.1 +/- 3.1; verbal IQ, 123.7 +/- 11.9). CT and TT carriers were combined in parallel to the original study by Papassotiropoulos et al. (2006). Twenty-nine subjects were CC carriers (17 males, 12 females; mean age, 66.8 +/- 8.6; years of formal education, 14.1 +/- 2.8; verbal IQ, 122.4 +/- 10.9). Schaper et al. (2008) observed a statistically significant poorer performance in total recall and in recognition in CC genotype carriers compared with the CT/TT genotype group. Free recall after interference and delayed free recall showed a trend toward difference between both groups. There was no difference between groups in verbal fluency.
Milnik et al. (2012) reported 2 random effects metaanalyses testing the association of rs17070145 with episodic and working memory. All currently available population-based association studies that investigated effects of rs17070145 on episodic or working memory were included in the analyses. Where performance measures for multiple domain-specific tasks were available for a given study population, averaged effect size estimates were calculated. The performed metaanalyses relied on 17 samples that were tested for episodic memory performance (8,909 participants) and 9 samples that had performed working memory tasks (4,696 participants). Milnik et al. (2012) reported a significant association of rs17070145 with both episodic (r = 0.068, p = 0.001) and working memory (r = 0.035, p = 0.018). Milnik et al. (2012) concluded that rs17070145 explains 0.5% of the variance for episodic memory tasks and 0.1% of the variance for working memory tasks in samples of primarily Caucasian background.
Duning et al. (2013) identified 2 common missense SNPS, met734 to ile (M734I; rs3822660) and ser735 to ala (S735A; rs3822659) (see 610533.0001), in exon 15 of the KIBRA gene that were in complete linkage disequilibrium with rs17070145 in intron 9. The 2 exonic SNPS are in the KIBRA C2 domain within a moderately conserved region preceding the alpha-helix of that domain. Duning et al. (2013) performed biochemical structural analyses and demonstrated that the KIBRA C2 domain has a bona fide lipid-binding capacity and a preference toward phosphatidylinositol 3-phosphate that is altered in the variant carrying I734 and A735 as well as a weaker interaction with PI(4P), PI(5P), and PI(4,5)P(2).
Pathogenesis
Palombo et al. (2013) investigated whether the KIBRA variant C-to-T polymorphism is associated with volume differences in the human hippocampus and whether specific subfields are differentially affected by KIBRA genotype. High-resolution MRI (T2-weighted, voxel size = 0.4 x 0.4 mm, in-plane) was used to manually segment hippocampal cornu ammonis (CA) subfields, dentate gyrus, and the subiculum as well as adjacent medial temporal lobe cortices in healthy carriers and noncarriers of the KIBRA T allele (rs17070145). Overall, Palombo et al. (2013) found that T carriers had a larger hippocampal volume relative to noncarriers. The structural differences observed were specific to the CA fields and dentate gyrus regions of the hippocampus, suggesting a potential neural mechanism for the effects of KIBRA on episodic memory performance reported previously.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MEMORY QUANTITATIVE TRAIT LOCUS
|
c3810089
| 8,244 |
omim
|
https://www.omim.org/entry/615602
| 2019-09-22T15:51:30 |
{"omim": ["615602"]}
|
A rare, genetic or acquired, cerebral malformation characterized by an intracerebral fluid-filled cyst or cavity with or without communication between the ventricle and subarachnoid space. Clinical manifestations depend on location and severity and may include hemiparesis, seizures, intellectual disability, and dystonia.
## Epidemiology
Point prevalence of acquired and genetic forms is unknown. However, birth prevalence of porencephaly is estimated at 1/19,000 in Japan and 1/28,500 in the USA.
## Clinical description
Porencephaly may manifest before or after birth. The cysts or cavities can be located anywhere within the cerebral parenchyma and are typically lined by smooth walls and surrounded by an atrophic cortex. The clinical picture is highly variable, even within affected families, with severe cases presenting major disability to mild cases with only slight, or even undetected, neurological involvement. The main clinical manifestations include hypotonia, microcephaly, spastic hemiparesis or quadriparesis, seizures, and global developmental delay. Intellectual disability is also a common finding and ranges from very mild to severe.
## Etiology
Prenatal- and postnatally-acquired cysts (acquired porencephaly) may be due to a number of causes including hemorrhage, local damage from ischemia or traumatic brain injury. Mutations in the COL4A1 (13q34) and COL4A2 (13q34) genes have been identified in familial (Familial porencephaly) and de novo cases. In these genetic cases, porencephaly results from antenatal or perinatal hemorrhage and is often associated with other brain abnormalities (bilateral white matter changes, calcifications, microbleeds) and ocular involvement (congenital cataract, retinal arterial tortuosity).
## Diagnostic methods
The diagnosis is suspected based on the clinical manifestations and is confirmed radiologically by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography showing characteristic intracerebral lesions. Cysts or cavities are well demarcated, contain cerebrospinal fluid and do not show contrast enhancement.
## Differential diagnosis
Differential diagnoses include arachnoid cyst, schizencephaly, ependymal cyst, encephalomalacia, hydranencephaly, and other COL4A1 or COL4A2 related diseases, including childhood stroke, CADASIL and retinal vasculopathy with cerebral leukodystrophy.
## Antenatal diagnosis
Ultrasonography may detect porencephaly prenatally after the 30th week of gestation.
## Genetic counseling
The pattern of inheritance for familial porencephaly is autosomal dominant. Genetic counseling should inform parents of the 50% risk of transmission for future offspring. Occasionally, genetic cases arise de novo.
## Management and treatment
No specific treatment is available for porencephaly. Treatment is therefore symptomatic and supportive and may include physical therapy, speech therapy, and anticonvulsant medication to treat seizures.
## Prognosis
Prognosis is variable and depends on the site and extent of the lesion.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Porencephaly
|
c0302892
| 8,245 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2940
| 2021-01-23T17:03:19 |
{"gard": ["7430"], "mesh": ["D065708"], "omim": ["175780", "614483"], "umls": ["C0302892"], "icd-10": ["Q04.6"]}
|
## Clinical Features
Bork et al. (1987) reported a 'new' type of ectodermal dysplasia with congenital hypotrichosis and uncombable hair, associated with juvenile cataracts, retinal pigmentary dystrophy, oligodontia, and brachymetacarpy. The condition was inherited as an autosomal dominant. Silengo et al. (1993) reported an isolated case. They illustrated the presence of supernumerary inferior lateral incisors and microdontia. The patient was mildly retarded. Scanning electron microscopy showed the presence of longitudinal grooves giving the typical appearance of pili canaliculi. Uncombable hair (see 191480), also referred to as 'spun-glass' hair, occurs as an isolated trait.
Inheritance
The transmission pattern of the syndrome described by Bork et al. (1987) was consistent with autosomal dominant inheritance.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Retinal pigmentary dystrophy \- Juvenile cataract Teeth \- Oligodontia \- Microdontia \- Supernumerary teeth GENITOURINARY External Genitalia (Male) \- Hypospadias SKELETAL Hands \- Brachydactyly \- Short proximal phalanges \- Short metacarpals Feet \- Brachydactyly SKIN, NAILS, & HAIR Hair \- Uncombable hair \- Pili canaliculi \- Pili trianguli ▲ 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
|
UNCOMBABLE HAIR, RETINAL PIGMENTARY DYSTROPHY, DENTAL ANOMALIES, AND BRACHYDACTYLY
|
c1860605
| 8,246 |
omim
|
https://www.omim.org/entry/191482
| 2019-09-22T16:32:12 |
{"mesh": ["C536576"], "omim": ["191482"], "orphanet": ["1264"], "synonyms": ["Alternative titles", "BORK SYNDROME"]}
|
Panner's disease is an osteochondrosis of the capitellum of the humerus, characterised by involvement of the dominant upper limb and onset before the age of 10 years. It results from lateral compression injuries of the elbow typically occurring in children practising sports such as baseball and throw. It should be distinguished from osteochondritis dissecans of the capitellum (see this term), occurring later, in adolescents. Management is symptomatic and consists in reducing the activities of the affected elbow for a prolonged period of time. Prognosis is good.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Panner disease
|
None
| 8,247 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97336
| 2021-01-23T17:59:29 |
{"icd-10": ["M92.0"], "synonyms": ["Aseptic necrosis of the capital humerus", "Osteochondrosis of the capital humerus"]}
|
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-33 (COXPD33) is caused by homozygous or compound heterozygous mutation in the C1QBP gene (601269) on chromosome 17p13.
Description
COXPD33 is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. The phenotype is highly variable, ranging from death in infancy to adult-onset progressive external ophthalmoplegia (PEO) and myopathy. A common finding is cardiomyopathy and increased serum lactate (summary by Feichtinger et al., 2017).
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Clinical Features
Feichtinger et al. (2017) reported 2 unrelated infants who presented soon after birth with a severe multisystem disorder associated with increased serum lactate and metabolic acidosis. Both infants died of cardiorespiratory insufficiency in the first days or weeks of life. One child had ventricular cardiomyopathy, congenital nephrosis with kidney failure, hypothyroidism, and encephalopathy with multiple hemorrhagic events. Postmortem examination of the kidney showed multifocal and diffuse cortical and pyramidal necrosis with hemorrhage, as well as scattered cortical tubular microcysts and partially or completely sclerosed glomeruli. The second patient, born of unrelated Japanese parents, had cardiomegaly and mild hepatomegaly with lipid accumulation; brain ultrasound did not reveal any abnormalities. Both pregnancies were complicated by oligohydramnios. Analysis of patient-derived tissues showed variable decreases in mitochondrial OXPHOS enzyme activities (complexes I, III, and IV).
### Clinical Variability
Feichtinger et al. (2017) reported 2 unrelated patients with a protracted course of COXPD33. A 22-year-old man, born of unrelated Austrian parents, presented with eye muscle weakness at age 5 years. He was subsequently found to have exercise intolerance with fatigue and increased serum creatine kinase, left ventricular hypertrophy, and progressive external ophthalmoplegia (PEO). Laboratory studies showed increased serum lactate, increased serum creatine kinase, and abnormal liver enzymes without structural abnormalities apparent on ultrasound. He also had subclinical evidence of a sensory peripheral neuropathy and low amplitude electroretinography. Hearing, kidney, and cognitive function were normal. The second patient was a 61-year-old man with adult-onset psychiatric problems who noted muscle weakness and rapidly progressive exercise intolerance at age 59 years. Other features included PEO, ptosis, muscle weakness, unstable gait due to lower limb weakness, and constipation. Detailed work-up showed left ventricular hypertrophy and sensorineural hypoacusia. He died of unknown causes in his seventies. Muscle biopsies of both patients showed multiple mtDNA deletions and combined OXPHOS enzyme deficiencies.
Inheritance
The transmission pattern of COXPD33 in the families reported by Feichtinger et al. (2017) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 unrelated patients with variable manifestations of COXPD33, Feichtinger et al. (2017) identified homozygous or compound heterozygous mutations in the C1QBP gene (601269.0001-601269.0006). The mutations were found by whole-exome or targeted sequencing and confirmed by Sanger sequencing; the mutations segregated in all 3 families who were tested. Patient tissue showed highly variable decreases in multiple OXPHOS protein subunits and complex activities. Patient-derived skeletal muscle and/or fibroblasts showed decreased or even absent levels of the C1QBP protein, suggesting that the mutations result in protein instability in some tissues, but the results were inconsistent. The mouse equivalents of 2 mutations found in 1 patient (patient S2) (L275P, 601269.0003 and G247W, 601269.0004) were unable to complement the mitochondrial respiratory defects in fibroblasts derived from C1qbp-null mice, consistent with a loss-of-function effect.
Animal Model
Yagi et al. (2012) found the C1qbp-null mice showed midgestation lethality associated with a severe developmental defect of the embryo. Primary embryonic fibroblasts isolated from mutant embryos showed severe dysfunction of the mitochondrial respiratory chain due to impaired mitochondrial protein synthesis. The findings suggested that C1qbp is required for functional mitoribosome formation to synthesize proteins in mitochondria.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss (1 patient) Eyes \- Progressive external ophthalmoplegia \- Ptosis \- Amblyopia \- Astigmatism CARDIOVASCULAR Heart \- Cardiomyopathy \- Left ventricular hypertrophy \- Cardiomegaly RESPIRATORY \- Cardiorespiratory insufficiency ABDOMEN Liver \- Hepatomegaly (1 patient) GENITOURINARY Kidneys \- Nephrosis (1 patient) \- Kidney failure (1 patient) MUSCLE, SOFT TISSUES \- Exercise intolerance \- Easy fatigue \- Weakness \- Myopathy NEUROLOGIC Peripheral Nervous System \- Sensory peripheral neuropathy (in some patients) METABOLIC FEATURES \- Metabolic acidosis ENDOCRINE FEATURES \- Hypothyroidism (1 patient) PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios (in some affected pregnancies) LABORATORY ABNORMALITIES \- Increased serum lactate \- Combined deficiency of mitochondrial respiratory complex activity, variable \- mtDNA depletion (in some patients) \- Increased serum creatine kinase \- Abnormal liver enzymes (in some patients) MISCELLANEOUS \- Four unrelated patients have been reported (last curated October 2017) \- Highly variable phenotype \- Neonatal onset and death in infancy (in some patients) \- Adult onset (in some patients) MOLECULAR BASIS \- Caused by mutation in the complement component C1q-binding protein gene (C1QBP, 601269.0001 ) ▲ 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
|
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 33
|
c4540209
| 8,248 |
omim
|
https://www.omim.org/entry/617713
| 2019-09-22T15:45:01 |
{"omim": ["617713"]}
|
A rare, mostly benign, neoplastic disease characterized by a primary tumor of the meninges, usually located intracranially (~90%) but spinal meningiomas occur as well. Clinical symptoms relate to the location of the tumor and may include seizures, focal neurological deficits (sensory-motor or visual symptoms, cranial nerve dysfunction), vascular complications (occlusion of cerebral blood vessels, deep venous thrombosis, pulmonary embolism), chronically increased intracranial pressure neurocognitive impairment and/or loss of bladder/anus sphincter control.
## Epidemiology
In adults, intracranial meningiomas represent approximately 30% of central nervous system tumors. The male to female ratio is 1:3.5.
## Clinical description
Whilst meningioma may appear at any age, it is predominantly diagnosed between the third and sixth decade of life. Meningiomas typically appear as broad-based dural hemispheric or oval lesions, attached to the dura mater. They most frequently occur supratentorially at the calvaria or skull base meninges, along the falx and in the parafalcine location, but can also be found attached to the tentorium, in the cerebello-pontine angle, within the optic nerve sheath, intraventricularly, or in the spinal canal. Lesions are classified into grade I (benign, most frequent), II (atypical), III (malignant) based on local invasiveness, cellular features and mitotic activity. Osseous destruction is indicative of atypical or malignant meningioma. Hyperostosis of adjacent skull bone is highly suggestive of benign meningioma. There are 15 immunohistological subtypes; features are subtype dependent but typically include whorl formation, nuclear pseudo-inclusions, pseudo-syncytial growth, and strong somatostatin-receptor subtype 2 (SSTR2) and epithelial membrane antigen expression.
## Etiology
The tumor most likely originates from arachnoid meningothelial cells. Several frequently mutated genes have been detected in meningiomas and include NF2, AKT1, SMO, PIK3CA, BAP1, TERT (promoter), SUFU, SMARCE1, and TRAF7.
## Diagnostic methods
The radiological diagnosis is made using contrast-enhanced MRI. Contrast-enhanced CT may also be used and is valuable for the detection of calcification within the tumor, hyperostosis of adjacent bone, and intraosseous tumor growth, especially in skull-base meningiomas. PET-based imaging using SSTR ligands is a helpful additional diagnostic tool and can be used to discriminate the lesion from healthy tissue or other entities. If imaging strongly suggests meningioma, histological verification is not mandatory; however, exclusion of rare differential diagnoses such as metastasis is recommended. Moreover, current diagnostic methods are not able to predict tumor grade which may have therapeutic implications.
## Differential diagnosis
The main differential diagnoses include other intracranial lesions, such as dural metastases, primary glial tumors that extend into the subarachnoid space, hematopoietic neoplasms (such as extra-axial non-Hodgkin lymphoma), pituitary neoplasms (e.g. adenomas or craniopharyngiomas), as well as inflammatory (rheumatoid arthritis, Wegener's granulomatosis, extra-axial neurosarcoidosis) and infectious diseases (tuberculosis, syphilitic gumma).
## Genetic counseling
Genetic counseling should be considered for patients with multiple meningioma, particularly in combination with ependymoma or schwannoma (NF2-related), and multiple spinal clear-cell meningioma (SMARCE1-related).
## Management and treatment
If treatment is required, surgery is the first option. Adjuvant therapies, mainly radiotherapy, may be required if location of the tumor is challenging, in case of significant residual disease or for grade III lesions. So far, there is no clear postoperative guideline for grade II meningiomas. Current systemic therapies have shown little or no response. Asymptomatic lesions (typically diagnosed incidentally) may be managed with observation and long-term follow-up with MRI until either symptoms develop, sustained growth occurs, or concerns of entrapment on sensitive structures arises.
## Prognosis
Tumor grade and extent of resection (based on Simpson grading) are the most important predictors of progression-free survival. For completely resected grade I lesions, the risk of tumor recurrence is low. However, meningiomas may confer an aggressive clinical course with multiple recurrences and, infrequently, metastases to other organs. Of note, long-term sequelae (e.g. impairment of neurocognitive functioning and quality of life) following treatment have been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Meningioma
|
c0025286
| 8,249 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2495
| 2021-01-23T17:40:12 |
{"gard": ["7015"], "mesh": ["D008579"], "omim": ["606190"], "umls": ["C0025286"], "icd-10": ["D32.9"]}
|
A number sign (#) is used with this entry because of evidence that posterior polymorphous corneal dystrophy-1 (PPCD1) is caused by heterozygous mutation in the promoter of the OVOL2 gene (616441) on chromosome 20p11.
Description
Posterior polymorphous corneal dystrophy (PPCD) is a rare disorder involving metaplasia and overgrowth of corneal endothelial cells (Krafchak et al., 2005). In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. Symptoms can range from very aggressive to asymptomatic and nonprogressive, even within the same family. The age of diagnosis is, most often, in the second or third decade of life.
Clinically, PPCD is characterized by vesicles, bands, and polymorphous opacities at the level of the Descemet membrane and corneal endothelium. Peripheral anterior iris adhesions, iris atrophy, pupillary ectropion, and corectopia may also develop. Occasional severe visual disability results from secondary glaucoma or corneal edema. On ultrastructural examination, corneal endothelial cells show fibroblastic and epithelial-like transformation (summary by Liskova et al., 2012).
### Genetic Heterogeneity of Posterior Polymorphous Corneal Dystrophy
Other forms of PPCD include PPCD2 (609140), caused by mutation in the COL8A2 gene (120252) on chromosome 1p34.3; PPCD3 (609141), caused by mutation in the ZEB1 gene (189909) on chromosome 10p; and PPCD4 (618031), caused by mutation in the GRHL2 gene (608576) on chromosome 8q22.
Clinical Features
This condition was first described by Koeppe (1916) under the name of keratitis bullosa interna, an appropriately descriptive designation. Schlichting (1941) noted depressions, vesicles, and polymorphous opacities in the Descemet membrane, with opacities in the deepest layers of the stroma, in father and 4-year-old daughter. Theodore (1939) reported affected members in 3 generations. McGee and Falls (1953) reported a family.
Maumenee (1960) examined 6 affected members over 3 generations of a family with corneal endothelial dystrophy that had previously been reported by Walsh (1957).
Rubenstein and Silverman (1968) observed a mother and 2 affected children. The mother and 1 child had rupture of the Descemet membrane, and the mother had glaucoma.
Pearce et al. (1969) reported a 5-generation British family in which 39 persons had congenital endothelial corneal dystrophy. A distortion of segregation ratio was noted in the offspring of affected females, with an excess of affected females and a deficiency of affected males. No biologic explanation could be found and it was concluded that the distorted sex ratio was a chance happening. The clouding of the cornea developed in the postnatal period and was usually well established by early childhood. Changes in the posterior cornea, namely, markedly reduced number of endothelial cells and thickening of the Descemet membrane, were thought to be primary.
Kirkness et al. (1987) reviewed 23 patients with what they called congenital hereditary corneal edema of Maumenee, including 6 from the family reported by Pearce et al. (1969) with autosomal dominant inheritance, and 17 from other families with either definite (8) or probable (9) autosomal recessive inheritance (see CHED; 217700). They commented that in spite of significant corneal clouding from birth or early childhood, visual development is often little impaired. Penetrating keratoplasty carries a relatively good surgical prognosis and can produce a substantial visual gain even when carried out late in life. Their experience suggested that the recessive form has an earlier age of onset and earlier age of presentation to medical attention. Kirkness et al. (1987) noted that advanced posterior polymorphous dystrophy may appear similar to CHED both clinically and histologically, and that some authorities have considered PPCD and CHED to represent parts of the spectrum of the same developmental anomaly.
Heon et al. (1995) studied a 5-generation family with posterior polymorphous dystrophy, previously described by Cibis et al. (1977) and Krachmer (1985), and identified 21 individuals with the characteristic endothelial abnormalities associated with the disorder. Seven of the affected patients had the diagnosis confirmed histopathologically following corneal transplantation. The diagnosis was made at age 4 years to 40 years (mean, 25 years). Visual acuity ranged from 20/20 to no light perception, with 26 eyes (61%) having a visual acuity of less than 20/40. Bilateral corneal transplants were required in 7 patients (33%). The 1 completely blind eye had become phthisical after 2 failed corneal transplants. Similarly, 1 of 2 eyes with light-perception vision had had a failed graft, while the other had never been operated upon but had severe stromal vascularization associated with poorly controlled glaucoma. Glaucoma was documented in 9 patients (42%), of whom 4 required surgery to control their intraocular pressures. None of the clinically unaffected family members were found to have glaucoma. Eight patients (38%) had iris abnormalities, and 1 of those had a prominent Schwalbe line with iridocorneal adhesions.
In a photo essay, Anderson et al. (2001) reviewed the clinical and histopathologic overlaps between posterior polymorphous membranous dystrophy and iridocorneal endothelial syndrome. PPCD is bilateral, usually asymptomatic, and usually nonprogressive; it occurs at all ages and shows no sex predilection. Sporadic iridocorneal endothelial syndrome is usually unilateral, symptomatic, and progressive; it presents at middle age and is more common in women. Corneal edema, glaucoma, and iris changes are more common in the iridocorneal endothelial syndrome. In PPCD, endothelial cells are more likely to display epithelial-like characteristics. The authors concluded that it is difficult to distinguish between these 2 endotheliopathies. They thought that an insult during embryogenesis might result in PPCD, whereas an insult later in corneal development might result in the iridocorneal endothelial syndrome. They also noted that the herpes simplex virus had been implicated as a cause in the iridocorneal endothelial syndrome.
Gwilliam et al. (2005) studied 2 large Czech families with PPCD, with 15 and 16 affected members, respectively. In the first family, 4 patients showed signs of secondary glaucoma, and 5 had undergone corneal transplant; in the second family, 7 had secondary glaucoma, and 4 had undergone transplantation. Changes observed on slit-lamp examination in affected members of both families included pathologic endothelium, geographic lesions, vesicles, and polymorphous opacities at the level of the Descemet membrane and the endothelium. Some family members exhibited corneal edema, band keratopathy, iridocorneal peripheral adhesions, iris atrophy, pupillary ectropion, and corectopia. Visual acuity in affected members of both families ranged from 20/20 to no light perception. Gwilliam et al. (2005) stated that PPCD in Czech patients is characterized by a high percentage of secondary glaucoma, present in 35% of patients, as well as of corneal graft surgery (29%), and noted that the French Canadian family studied by Heon et al. (1995) also showed a high percentage of secondary glaucoma and corneal grafts.
Yellore et al. (2007) examined 29 members of a large 5-generation American family with PPCD and classified 10 individuals as affected. The diagnosis was based on the presence of 1 or more characteristic corneal endothelial changes: scalloped bands, clustered vesicles with a surrounding gray halo, and/or geographic gray opacities. Four of the affected individuals had undergone corneal transplantation for visually significant corneal edema, 1 of whom also exhibited PPCD-associated corectopia and iridocorneal adhesions, with secondary angle-closure glaucoma in 1 eye and absolute glaucoma in the other. Histopathologic examination of the excised corneal button, when available, confirmed the diagnosis. The other 6 affected individuals were asymptomatic, with clinical features ranging from a few isolated endothelial vesicles to densely distributed endothelial vesicles and bands associated with mild corneal stromal edema. One family member, who had an isolated corneal endothelial opacity that was not typical of PPCD, was designated as having an indeterminate phenotype. None of the family members demonstrated any of the characteristic clinical features of keratoconus (see 148300).
Davidson et al. (2016) restudied the British kindred originally reported by Pearce et al. (1969), now comprising 36 affected individuals over 7 generations. Patients typically showed symptoms of epiphora and photophobia from birth, and corneal haze was noted by 1 year of age. Elevated intraocular pressure or iris abnormality was not present prior to corneal transplantation. Current data on 16 patients indicated that all had received at least 1 corneal graft or keratoplasty, as well as surgeries for secondary glaucoma. In addition, 3 had a keratoprosthesis, and 3 had undergone enucleation of an eye. Histologic examination of full-thickness corneas from 2 patients, aged 6 years and 11 years, revealed a thin and irregular Descemet membrane, reduced endothelial cell count, and accumulation of material posterior to the Descemet membrane, consistent with mild retrocorneal fibrosis. Davidson et al. (2016) also studied more than 100 affected individuals from 16 Czech PPCD pedigrees from the southwestern region of the Czech Republic, including 2 families originally described by Gwilliam et al. (2005) and 12 families reported by Liskova et al. (2012). Affected members of these families presented with irregularities of the otherwise smooth posterior corneal surface and often had focal opacities and geographic lesions of abnormal-appearing cells. The corneal endothelium showed occasional multilayering. Microscopic visualization of the specular reflection from the posterior corneal surface further documented abnormal endothelial cell morphology and irregularities of the posterior corneal surface. One-third of the patients had undergone keratoplasty in at least 1 eye, and approximately 30%, including some who had not undergone corneal transplantation, had secondary glaucoma. In contrast to the British kindred, none of the Czech patients had corneal edema at birth; the earliest manifestation was in two 5-year-old children, which was exceptionally early for the cohort. Of 75 genotyped Czech patients, only 6 had keratoplasty before the age of 18 years. The disease was fully penetrant with no systemic associations in the British kindred or the Czech families.
Pathogenesis
Heon et al. (1995) stated that the corneal endothelium is normally a single layer of cells that lose their mitotic potential after development is complete. In posterior polymorphous corneal dystrophy, however, the endothelium is often multilayered and has several other characteristics of an epithelium, including the presence of desmosomes, tonofilaments, and microvilli. These abnormal cells retain their ability to divide, and extend onto the trabecular meshwork to cause glaucoma in up to 40% of cases.
Jirsova et al. (2007) demonstrated that the abnormal endothelium of PPCD patients expressed a mixture of cytokeratins, with KRT7 (148059) and KRT19 (148020) predominating. In terms of KRT composition, the aberrant PPCD endothelium shared features of both simple and squamous stratified epithelium with a proliferative capacity. Jirsova et al. (2007) suggested that the wide spectrum of KRT expression was most probably not indicative of the transformation of endothelial cells to a distinct epithelial phenotype, but more likely reflected a modified differentiation of metaplastic epithelium.
Population Genetics
Liskova et al. (2012) identified 113 affected individuals from 19 Czech families with PPCD, which they stated was the highest reported prevalence of PPCD worldwide. Correlated to the population, at least 1 in 100,000 inhabitants of the Czech Republic has PPCD. Because of the relative rarity of the disorder, a founder effect was suspected (see MAPPING).
Mapping
In a large family with 21 members affected with posterior polymorphous dystrophy, previously described by Cibis et al. (1977) and Krachmer (1985), Heon et al. (1995) demonstrated linkage with short tandem repeat polymorphism (STRP) markers on 20q. The highest observed lod score was 5.54 at theta = 0.0 with marker D20S45. Analysis of recombination events in 4 affected individuals revealed that the disease gene lies within a 30-cM interval between markers D20S98 and D20S108.
In a large family with autosomal dominant congenital endothelial corneal dystrophy, previously reported by Pearce et al. (1969) and Kirkness et al. (1987) and believed to represent an autosomal dominant form of CHED (see 217700), Toma et al. (1995) found linkage with markers on chromosome 20. The highest observed lod score was 7.20 at theta = 0.026 with marker D20S114. Multipoint analysis gave a maximum lod score of 9.34 between D20S48 and D20S471. Toma et al. (1995) noted that this 2.7-cM region lies within the 30-cM region where the gene for PPCD is located. Analysis of the evidence on cytogenetic location of markers used in the mapping of autosomal dominant CHED and PPCD showed that both loci are in the pericentric region of chromosome 20, i.e., 20p11.2-q11.2. The authors suggested that PPCD and the autosomal dominant form of CHED (so-called 'CHED1'), might be allelic; see NOMENCLATURE.
Aldave et al. (2013) reviewed the genetics of the corneal endothelial dystrophies. Noting the clinical, histopathologic, and ultrastructural similarities between affected individuals from the 'CHED1' family (Pearce et al., 1969) that was mapped to chromosome 20 by Toma et al. (1995) and the findings in PPCD1 patients who map to an overlapping region of chromosome 20, Aldave et al. (2013) stated that it is most plausible that the 'CHED1' family actually has PPCD1.
Molecular Genetics
In a large British kindred with PPCD mapping to chromosome 20p, which was originally reported by Pearce et al. (1969), Davidson et al. (2016) performed whole-genome sequencing and identified a heterozygous duplication within the promoter of the OVOL2 gene (616441.0001) that segregated fully with disease in the family and was not found in 209 ethnically matched British control samples. In 16 Czech PPCD1 pedigrees, including 2 families originally described by Gwilliam et al. (2005) and 12 families previously studied by Liskova et al. (2012), Davidson et al. (2016) identified heterozygosity for a c.-370T-C mutation within the OVOL2 promoter (616441.0002) that also segregated fully with disease and was not found in controls. Screening of 8 additional British and Czech probands with genetically unsolved PPCD revealed 2 more mutations in the OVOL2 promoter in 2 British probands (616441.0003 and 616441.0004). Although expression of OVOL2 was not observed in human fetal or adult corneal endothelium, Davidson et al. (2016) noted that the OVOL2 promoter region has binding sites for multiple transcription factors, and that the majority of these transcription factors are expressed in human corneal endothelial cells. Functional analysis in transfected HEK293 cells demonstrated that each of the 4 mutants significantly increased promoter activity in vitro. In addition, Davidson et al. (2016) stated that OVOL2 is a known direct repressor of the PPCD3-associated ZEB1 gene, and suggested that dysregulation of the OVOL2-ZEB1 feedback loop was likely relevant to the pathogenetic mechanism in PPCD1.
### Associations Pending Confirmation
See 605020.0002 for discussion of a possible association between variation in the VSX1 homeobox gene and PPCD.
### Exclusion Studies
By SSCP analysis and direct sequencing in the large family with PPCD that was mapped to chromosome 20 by Heon et al. (1995), Heon et al. (2002) excluded mutation in the VSX1 gene.
In 2 Czech families with PPCD mapping to chromosome 20, Gwilliam et al. (2005) excluded the candidate gene VSX1 and suggested that VSX1 might not be a common cause of corneal endothelial dystrophies.
In 2 families with PPCD mapping to chromosome 20 in which mutation in the VSX1 gene had been excluded, 1 of which was the family originally studied by Heon et al. (1995), Hosseini et al. (2008) analyzed 3 candidate genes, RBBP9 (602908), ZNF133 (604075), and SLC24A3 (609839), but did not find any mutations.
In the probands from 2 Czech families with PPCD that was mapped to chromosome 20p11.2 by Gwilliam et al. (2005), Liskova et al. (2012) sequenced the candidate gene ZNF133 but found no pathogenic variants. In addition, dense chromosome 20 CGH analysis in 1 affected individual did not reveal any microdeletions or duplications at 20p12.1-p11.23.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Photophobia (in some patients) \- Epiphora (in some patients) \- Decreased vision (in most patients) \- Corneal clouding \- Corneal edema (in some patients) \- Iridocorneal adhesions (in some patients) \- Iris atrophy (in some patients) \- Pupillary ectropion (in some patients) \- Corectopia (in some patients) \- Band keratopathy (in some patients) \- Vesicles at Descemet membrane \- Focal opacities on posterior corneal surface \- Geographic lesions on posterior corneal surface \- Thickening of non-banded zone of Descemet membrane \- Irregular thinning of Descemet membrane (in some patients) \- Irregular white areas on posterior surface of Descemet membrane \- Accumulation of material posterior to Descemet membrane (in some patients) \- Beaten copper appearance on retroillumination \- Reduced number of endothelial cells of posterior cornea \- Abnormal morphology of endothelial cells of posterior cornea \- Multilayering of corneal endothelium \- Absence of hexagonal endothelial cell pattern in zone of specular reflection \- Secondary glaucoma MISCELLANEOUS \- Interfamilial and intrafamilial variability in severity of symptoms \- Variable age at onset \- Some affected family members are asymptomatic \- Visual acuity varies from 20/20 to no light perception MOLECULAR BASIS \- Caused by mutation in the promoter of the OVO-like-2 gene (OVOL2, 616441.0001 ) ▲ 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
|
CORNEAL DYSTROPHY, POSTERIOR POLYMORPHOUS, 1
|
c0339284
| 8,250 |
omim
|
https://www.omim.org/entry/122000
| 2019-09-22T16:42:53 |
{"doid": ["0110855"], "omim": ["122000"], "orphanet": ["98973"], "synonyms": ["Alternative titles", "POSTERIOR POLYMORPHOUS CORNEAL DYSTROPHY", "CORNEAL DYSTROPHY, HEREDITARY POLYMORPHOUS POSTERIOR", "MAUMENEE CORNEAL DYSTROPHY", "CORNEAL ENDOTHELIAL DYSTROPHY 1, AUTOSOMAL DOMINANT, FORMERLY"]}
|
A number sign (#) is used with this entry because blepharophimosis, ptosis, and epicanthus inversus syndrome, either with premature ovarian failure (BPES type I) or without (BPES type II), is caused by autosomal dominant mutation in the FOXL2 gene (605597) on chromosome 3q22. Rare instances of homozygous mutation in the FOXL2 gene have been reported.
Clinical Features
Vignes (1889) probably first described this entity, a dysplasia of the eyelids. In addition to small palpebral fissures, features include epicanthus inversus (fold curving in the mediolateral direction, inferior to the inner canthus), low nasal bridge, and ptosis of the eyelids (Sacrez et al., 1963; Johnson, 1964; Smith, 1970). The condition should be considered distinct from congenital ptosis (178300).
Owens et al. (1960) updated the pedigree of a family that was first reported by Dimitry (1921), which had affected members in 6 generations. The patients had the classic syndrome triad of blepharophimosis, ptosis, and epicanthus inversus. Raviotta (1971), a physician who is an affected member of the pedigree studied by Owens et al. (1960), provided a first-hand description. Smith (1970) described affected mother and daughter.
Moraine et al. (1976) suggested that female infertility is a pleiotropic effect of the gene. Townes and Muechler (1979) reported a family in which all affected females had primary ovarian failure. They had a normal female karyotype and normal breast development; pubic and axillary hair was scant, but in a normal female distribution. Laparoscopy showed a small uterus and small atrophic ovaries.
Zlotogora et al. (1983) suggested that there are 2 forms of BPES: type I with infertility of affected females and type II with transmission by both males and females. The infertility is inherited as an autosomal dominant sex-limited trait. Jones and Collin (1984) reviewed 37 known cases; of the 6 females of child-bearing age, 1 had primary amenorrhea with raised gonadotropins and low estrogen and progesterone.
Oley and Baraitser (1988) provided an illustrated review of BPES. Fraser et al. (1988) and Smith et al. (1989) described 4 women from 3 families with blepharophimosis, epicanthus inversus, and ptosis who had premature ovarian failure. Two were sisters; they had another affected sister who was not investigated. Two of the 3 families had multiple affected members. Smith et al. (1989) suggested that these cases, type I in the classification of Zlotogora et al. (1983), represented a 'contiguous gene syndrome' (Schmickel, 1986) with a combination of blepharophimosis and familial precocious ovarian failure.
Temple and Baraitser (1989) reported a family in which an uncle and nephew were clearly affected. The carrier mother had no abnormality as an adult, but photographs of her as a child showed unilateral minimal ptosis without epicanthus inversus. Finley et al. (1990) studied 14 sporadic cases of this syndrome (which they abbreviated BPEI) and found an apparent maternal age effect, but no paternal age effect.
Panidis et al. (1994) described blepharophimosis in 2 sisters, a brother, and their father. The elder sister presented initially with 'resistant ovary syndrome' and thereafter true premature menopause, while the younger sister presented with resistant ovary syndrome.
Cunniff et al. (1998) reported 22 individuals referred for genetic evaluation because of blepharophimosis. The blepharophimosis syndrome was present in 14 of the 22, and was familial in 5, sporadic in 9. The other 8 children had a malformation syndrome other than the blepharophimosis syndrome. All 8 were mentally retarded or developmentally delayed. Two of the 8 had recognized disorders, branchiootorenal syndrome (113650) in one and a ring chromosome 4 in the other; the remaining 6 had unrecognized malformation syndromes, each distinctive from the others.
Cytogenetics
Fukushima et al. (1990) reported a newborn infant with BPES and a de novo balanced 3q23;4p15 reciprocal translocation. In a father and son with typical BPES, de Die-Smulders et al. (1991) found an apparently balanced translocation, t(3;11)(q21;q23). Since blepharophimosis, ptosis, and microphthalmia are consistent features in patients with an interstitial deletion of band 3q2 (Alvarado et al., 1987), the BPES gene was likely to be located at 3q2.
Williamson et al. (1981) described an 8-year-old boy with marked blepharophimosis, ptosis, sad fixed face, joint contractures, and several other anomalies associated with a del(3)(q22.1-q24), suggestive of Schwartz-Jampel syndrome (255800). Fujita et al. (1992) reported a 6-year-old boy with de novo 46,XY,del(3)(q12q23) and bilateral blepharophimosis, ptosis, epicanthus inversus, as well as multiple other anomalies, including joint contractures and a fixed facial appearance. However, in both patients, normal EMG findings and normal skeletal films excluded the diagnosis of Schwartz-Jampel syndrome. Fujita et al. (1992) suggested that the blepharophimosis sequence in these patients may represent a contiguous gene syndrome. Other relevant cases had been reported by Martsolf and Ray (1983), Al-Awadi et al. (1986), and Okada et al. (1987).
Jewett et al. (1992) reported a child with classic features of BPES with developmental delay and an interstitial deletion of a single band within 3q: del(3)(q21.3-q22.3). De Almeida et al. (1993) described an apparently balanced translocation, t(3;8)(q23;p21.1), in a child with mild mental retardation, blepharophimosis, ptosis, telecanthus, and epicanthus inversus. The patient was microcephalic with mild dysmorphism and minor anomalies.
Reinforcement of the suggestion that the BPES gene is located at 3q2 was provided by Fryns et al. (1993), who described a 6-year-old mentally retarded boy, born to normal parents, who had typical signs of the disorder and a de novo interstitial deletion of chromosome 3: del(3)(q22.3-q23). Ishikiriyama and Goto (1993) described a girl with BPES, microcephaly of postnatal onset, mild developmental retardation, and a de novo deletion del(3)(q22.2q23). Jewett et al. (1993) described an interstitial deletion of 3q22. From a review of the other reported cases, they concluded that a locus for eyelid development is situated at the interface of bands 3q22.3 and 3q23. Wolstenholme et al. (1994) reported a sporadic case of BPES associated with prenatally diagnosed diaphragmatic hernia and interstitial deletion of the long arm of chromosome 3, del(3)(q21q23). Ishikiriyama and Goto (1994) suggested that the association of BPES with microcephaly or other manifestations of 'general hypoplasia of the CNS' such as hypotrophy of the cerebellar vermis may represent a contiguous gene syndrome because of the observed association with interstitial deletions.
Boccone et al. (1994) described a de novo, apparently balanced, reciprocal translocation between the long arms of chromosomes 3 and 7 in a 2-year-old male with BPES; the breakpoints were 3q23 and 7q32. Warburg et al. (1995) described 3 unrelated, mentally retarded boys with typical BPES, each of whom had chromosomal aberrations. One of them was thought to have a deletion of 3p25 and a second was thought to have a loss of band 3q23. The third patient, however, had a del(7)(q34). The phenotypes of the 2 patients with the chromosome 3 aberrations were similar, but the third had, in addition to features of BPES, genital malformations resembling those of the Smith-Lemli-Opitz syndrome (SLO; 270400), which maps to 7q34-qter. The patient had a palatal ridge as well as a single mesial maxillary tooth, suggesting the holoprosencephaly sequence, but CT scans of the brain were normal. Fryns (1995) described a patient in whom BPES was associated with the Langer type of mesomelic dwarfism (249700). He suggested that a submicroscopic deletion of 3q22.3-q23 was responsible for the concurrence of the 2 disorders. Karimi-Nejad et al. (1996) reported a sporadic translocation t(X;3)(p22;q21) in a girl with typical manifestations of BPES.
Common clinical features of patients with 3q23 deletion include BPES, growth and mental retardation, microcephaly, ear and nose dysmorphism, and joint and digital abnormalities. Chandler et al. (1997) described a 3-year-old girl with BPES, mental retardation, facial dysmorphism, and camptodactyly. In addition, she had a congenitally small larynx and severe, chronic feeding difficulties. Chromosome studies revealed an interstitial deletion, del(3)(q23-q25). Cai et al. (1997) reported a 3.5-year-old girl with an unbalanced translocation 46,XX,der(7)t(3;7)(q26-qter;q+) resulting in trisomy 43q26-qter. The child had blepharophimosis, unilateral ptosis, high forehead, microcephaly, and mental retardation, but did not have epicanthus inversus. Cai et al. (1997) suggested that BPES is genetically heterogeneous and may be the result of a contiguous gene defect.
Mapping
Small et al. (1995) studied 2 BPES families with autosomal dominant inheritance and obtained a maximum lod score of 3.23 using the markers rhodopsin (180380), located at 3q21-q24; prostate acid phosphatase (171790), located at 3q21-q23; and D3S1238. No evidence of genetic heterogeneity was observed. In a large French pedigree, Amati et al. (1995) also mapped the BPES gene to 3q23. With linkage studies in 2 large families, Harrar et al. (1995) confirmed the assignment of BPES to 3q21-q24 (lod score of 3.2 at D3S1237).
Amati et al. (1996) showed that the form of BPES associated with premature ovarian failure (type I of Zlotogora et al. (1983)) maps to 3q22-q23, the same chromosomal region as does the form without POF (type II).
Lawson et al. (1995) mapped a translocation breakpoint associated with BPES to the D3S1316-D3S1615 interval. The markers in this region were subsequently shown to lie in a different order, with the BPES locus mapping to the 1-cM D3S1576 and D3S1316 interval. Toomes and Dixon (1998) constructed a physical map, consisting of 60 YAC clones and 1 bacterial artificial chromosome, that spanned this region. YAC end isolation led to the creation of novel STSs that were used to reduce the size of the BPES critical region to a 280-kb interval, which was cloned in 2 nonchimeric YACs.
Praphanphoj et al. (2000) identified another case of BPES associated with a de novo reciprocal translocation involving 3q23. By fluorescence in situ hybridization analysis using an assortment of probes, they found that the breakpoint in their patient lay proximal to that in the patient studied by De Baere et al. (1999), within a 10.5-kb interval.
Inheritance
The transmission pattern of BPES in the original family described by Dimitry (1921) was consistent with autosomal dominant inheritance (Owens et al., 1960). Crisponi et al. (2001) found that BPES types I and II are autosomal dominant traits.
Nallathambi et al. (2007) and Kaur et al. (2011) described an Indian family with autosomal recessive inheritance of BPES type I and type II, respectively.
Molecular Genetics
By positional cloning, Crisponi et al. (2001) identified the FOXL2 gene and identified mutations resulting in truncated proteins in affected individuals with both types I and II BPES (605597.0001 and 605597.0002). Consistent with an involvement in those tissues, FOXL2 was found to be selectively expressed in the mesenchyme of developing mouse eyelids and in adult ovarian follicles; in adult humans, it appeared predominantly in the ovary.
In 2 sporadic patients and 2 families with BPES, Beysen et al. (2005) identified 4 overlapping extragenic microdeletions 230 kb upstream of the FOXL2 gene. The shortest region of deletion overlap contains several conserved nongenic sequences harboring putative transcription factor-binding sites and representing potential long-range cis-regulatory elements. Affected females in the 2 families had BPES type II; BPES type could not be assessed in the sporadic patients. In another family with BPES, Beysen et al. (2005) identified an approximately 188-kb microdeletion downstream of the FOXL2 gene. The father of the 2 affected half-sisters was unaffected, suggestive of germinal mosaicism; quantitative analysis using 3 SNPs located in the deletion showed that about 10% of paternal germ cells and 5% of somatic peripheral blood lymphocytes carried the mutation.
Vincent et al. (2005) reported an 18-month-old girl with sporadic BPES and bilateral type 1 Duane syndrome (see 126800), in whom they identified a heterozygous duplication of 10 alanine residues in the FOXL2 gene (605597.0002).
In 3 affected males and 1 affected female of a consanguineous Indian family with BPES type I, Nallathambi et al. (2007) identified a homozygous duplication in the FOXL2 gene (605597.0018), resulting in a polyalanine expansion from 14 to 19 residues (Ala19). Several unaffected relatives were heterozygous for the mutation, indicating autosomal recessive inheritance in this family. The affected 30-year-old woman had amenorrhea and impaired fertility, consistent with ovarian dysfunction. Nallathambi et al. (2007) noted that ala19 is the shortest polyalanine expansion (+5) described in the FOXL2 gene and may confer residual enzyme activity.
In an Indian cohort comprising 6 familial and 2 sporadic cases of BPES type I or type II, Kaur et al. (2011) identified 6 heterozygous mutations in the FOXL2 gene, 3 of which were novel (see, e.g., E69K; 605597.0020). In the family with BPES type II and the E69K mutation (family BPES6), some patients were heterozygous and others homozygous; patients homozygous for the mutation had more a more severe phenotype. In another family, an affected female also had polycystic ovarian disease. Kaur et al. (2011) noted that mutations in the region downstream of the forkhead domain were predominantly responsible for BPES among Indian patients.
Animal Model
Using piggyBac (PB) insertional mutagenesis, Shi et al. (2014) created a line of mice with a modest yet significant reduction in Foxl2 expression. Homozygous PB/PB mice began to lose weight approximately 2 weeks after birth, and most died within the first month of life. At 3 weeks of age, they showed significant overgrowth of mandibular incisors with malocclusion, and some showed palpebral anomalies and periocular hair loss. Surviving female PB/PB mice were subfertile, with smaller than normal ovaries and uteri. Shi et al. (2014) concluded that PB/PB mice recapitulated the craniofacial and ovarian conditions of type I BPES patients. The authors mapped the PB insertion site to a region approximately 160 kb upstream of the Foxl2 transcription start site and approximately 10 kb upstream of an element, ECF1, that showed a high degree of conservation among goat, mouse, and human. ECF1 functioned as an enhancer in reporter gene assays and interacted directly with the Foxl2 promoter in chromosome conformation capture assays. Shi et al. (2014) noted that BPES patients with balanced translocations and chromosome breakpoints 130, 160, or 171 kb upstream of FOXL2 have been reported. The authors hypothesized that these translocations may isolate transcription regulatory elements, including the human ECF1 ortholog, leading to FOXL2 misregulation.
History
So-called 'BPES3,' which had been mapped in an Indian family to 7p, has been shown to be part of the phenotypic spectrum of Saethre-Chotzen syndrome (SCS; 101400) and to result from mutation in the TWIST1 gene (601622) on 7p21. This finding supported locus homogeneity of BPES at 3q22 (Dollfus et al., 2001).
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Characteristic backward head tilt Ears \- Simple ears \- Cup-shaped ears Eyes \- Blepharophimosis \- Ptosis \- Telecanthus \- Epicanthus inversus \- Pronounced convex arch of eyebrows \- Microphthalmia \- Microcornea \- Strabismus \- Hypermetropia \- Nystagmus Nose \- Flat, broad nasal bridge Mouth \- High-arched palate CHEST Breasts \- Normal breast development GENITOURINARY External Genitalia (Female) \- Scant pubic hair Internal Genitalia (Female) \- Small uterus \- Small atrophic ovaries SKIN, NAILS, & HAIR Hair \- Pronounced convex arch of eyebrows \- Scant pubic hair (females) \- Scant pubic and axillary hair (females) ENDOCRINE FEATURES \- Elevated gonadotropins \- Low estrogen and progesterone \- Amenorrhea \- Female infertility \- Menstrual irregularities \- Premature ovarian failure MISCELLANEOUS \- Two types - one with premature ovarian failure (BPES type 1) and one without POF (BPES type 2) MOLECULAR BASIS \- Caused by mutation in the forkhead transcription factor FOXL2 gene (FOXL2, 605597.0001 ) ▲ 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
|
BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS
|
c0220663
| 8,251 |
omim
|
https://www.omim.org/entry/110100
| 2019-09-22T16:44:25 |
{"doid": ["14778"], "mesh": ["C562419"], "omim": ["110100"], "orphanet": ["261579", "126", "261559", "261572"], "synonyms": ["Blepharophimosis types 1 and 2 due to copy number variations", "Blepharophimosis-epicanthus inversus-ptosis due to a CNV"], "genereviews": ["NBK1441"]}
|
Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. Lymph fluid helps exchange immune cells, proteins, and other substances between the blood and tissues.
LAM is found almost exclusively in women. It often occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.
Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).
The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.
Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.
## Frequency
LAM occurs in approximately 30 percent of women with tuberous sclerosis complex. Sporadic LAM, which occurs without tuberous sclerosis complex, is estimated to affect 3.3 to 7.4 per million women worldwide. This condition may be underdiagnosed because its symptoms are similar to those of other lung disorders such as asthma, bronchitis, and chronic obstructive pulmonary disease.
## Causes
Mutations in the TSC1 gene or, more commonly, the TSC2 gene, cause LAM. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.
When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way, resulting in the tumors and cysts associated with LAM.
It is not well understood why LAM occurs predominantly in women. Researchers believe that the female sex hormone estrogen may be involved in the development of the disorder.
### Learn more about the genes associated with Lymphangioleiomyomatosis
* TSC1
* TSC2
## Inheritance Pattern
Sporadic LAM is not inherited. Instead, researchers suggest that it is caused by a random mutation in the TSC1 or TSC2 gene that occurs very 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. When a mutation occurs in the other copy of the TSC1 or TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM. These women typically have no history of this 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
|
Lymphangioleiomyomatosis
|
c0751674
| 8,252 |
medlineplus
|
https://medlineplus.gov/genetics/condition/lymphangioleiomyomatosis/
| 2021-01-27T08:25:09 |
{"gard": ["3319"], "mesh": ["D018192"], "omim": ["606690"], "synonyms": []}
|
A number sign (#) is used with this entry because tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia due to PTS deficiency (HPABH4A) is caused by mutation in the gene encoding 6-pyruvoyl-tetrahydropterin synthase (PTS; 612719).
Description
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001).
HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene.
Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.
Clinical Features
Kaufman et al. (1978) studied a boy with what appeared to be classic phenylketonuria who showed neurologic abnormalities, including hypotonia and delayed motor development, despite good dietary control of blood levels of phenylalanine from the age of 25 days. Tetrahydrobiopterin was only 10% of normal in liver, and serum and urinary levels of biopterin-like compounds were low. Furthermore, serum biopterin did not increase with phenylalanine load, as it would in both normal individuals and in patients with PKU. A defect in biopterin synthesis was postulated. Phenylalanine loading showed the mother to be a heterozygote. The father was considered to be intermediate between normal and heterozygous. Similar cases were reported by Rey et al. (1977) and Milstien et al. (1977).
Using an assay for PTS activity in red blood cells, Niederwieser et al. (1987) identified 4 patients in 3 families with 'peripheral' tetrahydrobiopterin deficiency. They were characterized biochemically by a BH4-responsive hyperphenylalaninemia, a high neopterin:biopterin ratio in urine and plasma, but normal or even elevated concentrations of neurotransmitter metabolites in the cerebrospinal fluid (CSF). The authors concluded that although residual PTS activity was sufficient to cover modest BH4 requirements of tyrosine hydroxylase and tryptophan hydroxylase in the brain, it was not enough to cover the much higher BH4 requirements of PAH in the liver, depending on the phenylalanine intake, protein turnover, and age. Thus, the so-called peripheral form results in hyperphenylalaninemia with only mild or no neurologic symptoms.
Scriver et al. (1987) reported deficient red cell PTS activity as the cause of persistent postnatal hyperphenylalaninemia in 4 probands and 1 sib. The metabolic findings were associated with a benign clinical presentation and normal biopterin levels in cerebrospinal fluid in the newborn period. Impaired development was apparent at 3 months in 1 proband not treated early. Treatment with oral BH4 restored adequate phenylalanine hydroxylase activity; it also maintained or improved CNS function. Red cell activity of PTS in homozygotes or compound heterozygotes was less than 10% of normal. Obligatory heterozygotes in some instances showed levels of enzyme activity lower than expected, suggesting genetic heterogeneity at the PTS locus.
Dhondt et al. (1988) described a patient with clinical features similar to those of the peripheral form of BH4 deficiency: hyperphenylalaninemia with an increase in neopterin to biopterin ratio in the urine, decrease in blood phenylalanine levels on tetrahydrobiopterin loading, biopterin and neurotransmitter metabolite levels within the normal range in the CSF, and a clinically normal appearance at 9 months with minimal neurologic signs on elevation of the plasma phenylalanine levels. In this patient, an unidentified pteridine-like compound was found in the urine and in the CSF, leading the authors to suggest the existence of an unidentified block in the biopterin biosynthetic pathway.
Dudesek et al. (2001) reported long-term follow-up information on 5 patients with PTS deficiency from 4 different families and provided a review of the disorder. Patients with BH4 deficiency resulting from a defect in the PTS gene presented with neurologic signs linked to impaired catecholamines and serotonin synthesis. Most infants were born small for gestational age, and most were seen at an average age of 4 months, although symptoms sometimes became evident in the first weeks of life. Frequent symptoms of PTS deficiency resembled those of Parkinson disease (PD; 168600), indicating a lack of dopamine in the basal ganglia. Extrapyramidal signs included characteristic truncal hypotonia, increased limb tone, postural instability, hypokinesia, choreatic or dystonic limb movements, gait difficulties, hypersalivation due to swallowing difficulties, and oculogyric crises. There were 2 main phenotypes. The more common was the severe 'central' form, accompanied by abnormalities of biogenic amines in the CSF. These patients required a combined treatment of BH4 and neurotransmitter precursors, and needed monotherapy with BH4 in order to maintain normal plasma phenylalanine levels. In contrast, the rare mild 'peripheral' (atypical) form of PTS deficiency was characterized by normal neurotransmitter homeostasis and moderate or transient hyperphenylalaninemia. In patients with the mild peripheral form, hyperphenylalaninemia did not recur when BH4 therapy was discontinued.
Clinical Management
Niederwieser et al. (1982) found that treatment with L-sepiapterin (see 182125) was more effective than tetrahydrobiopterin therapy, and pointed to evidence that biopterin biosynthesis in the kidney and liver proceeds via a dioxo compound and L-sepiapterin.
McInnes et al. (1984) presented studies that indicated the complexity in replacement therapy with L-DOPA and 5-hydroxytryptophan (5-HTP). The treatment may be partially effective, however, in biopterin-deficient patients who are unresponsive to high doses of BH4. McInnes et al. (1984) used a lipophilic analog of BH4, 6-methyltetrahydropterin (6MPH4), which crosses the blood-brain barrier. Although the hyperphenylalaninemia was controlled and significant concentrations of 6MPH4 in cerebrospinal fluid were obtained, neurologic improvement and stimulation of monoamine synthesis in the nervous system were not achieved.
In 10 Chinese patients with BH4 deficiency due to PTS mutations, Chien et al. (2001) found that BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within the normal range, and administration of L-DOPA itself prevented seizures. However, the average IQ of these patients was only 76 +/- 14, with a range of 56 to 98. Statistically, the age of starting medication, including 5-hydroxytryptophan, was inversely correlated with IQ scores of these patients. Chien et al. (2001) suggested that the combination of BH4, L-DOPA, and 5-HTP as the standard protocol for the treatment of BH4 deficiency be started as early as possible, although prenatal brain damage may already exist.
Lee et al. (2006) reported long-term follow-up of 10 PTS-deficient Taiwanese patients who had delayed treatment with tetrahydrobiopterin, L-DOPA, and 5-HTP. The patients included 2 pairs of sibs. Five patients had severe psychomotor retardation with central hypotonia, were bedridden, lacked eye contact, and were in a vegetative-like state. Two other patients had psychomotor retardation and central hypotonia, but were not as severely affected as the first 5 patients. They were able to articulate single words and walked with unstable gait. These 8 patients had multiple seizures per day and were classified as severe. The remaining 2 patients had mild mental retardation, milder spasticity, and were in special educational schools. All patients showed marked improvements in neurologic signs and symptoms after initiation of treatment. Patients with recurrent seizures showed a marked decrease in the frequency of seizures, and oculogyric spasm improved gradually after 3 to 5 days. Other neurologic manifestations, including limb spasticity, hypotonia, dysphagia, and hypersalivation gradually improved over a 6- to 12-month period. The 2 patients with milder spasticity had resolution of spasticity after initiation of therapy. Eight of the patients showed increases in IQ scores after many years. One patient began walking and talking after 4 years of treatment. Most patients discontinued 5-HTP treatment due to a drug shortage, without significant adverse effects. Lee et al. (2006) concluded that treatment is beneficial in all cases.
Molecular Genetics
Thony et al. (1994) identified mutations in the PTS gene (e.g., 612719.0001) in patients with BH4-deficient hyperphenylalaninemia.
Oppliger et al. (1997) identified 4 novel mutations in 4 Italian families with PTS deficiency.
Thony and Blau (1997) reviewed the spectrum of mutations in the PTS gene resulting in tetrahydrobiopterin deficiency. They stated that compound heterozygous or homozygous mutations spread over all 6 exons of the gene can cause an autosomal recessive variant of hyperphenylalaninemia, mostly accompanied by a deficiency of dopamine and serotonin.
Population Genetics
Liu et al. (1998) identified 7 single-base mutations in Chinese cases of PTS-deficient hyperphenylalaninemia. In all, 38 PTS mutant alleles from 19 unrelated Chinese families were studied. Two common mutations, N52S (612719.0004) and P87S (612719.0005), accounted for 71% of the mutant alleles. The N52S mutation accounted for 48% of the southern Chinese PTS mutations, but only 1 (9%) of the northern Chinese PTS mutant alleles was found to be N52S. Clinically, the V56M (612719.0006) mutation was found to be associated with the mild form of PTS deficiency, whereas R25G (612719.0001), N52S, P87S, and D96N (612719.0009) were found mainly in patients with severe clinical symptoms.
Chien et al. (2001) reported 10 cases of BH4 deficiency among 1,337,490 newborns screened in a Chinese population in Taiwan. They postulated that the high incidence in the Taiwanese population may be explained by a founder effect, since all of the patients were found to have PTS gene mutations, and grouping the common N52S and P87S mutations together constituted 88.9% of the disease alleles.
Nomenclature
Danks et al. (1978, 1979) referred to the BH4-dependent HPA disorders as 'malignant hyperphenylalaninemia' since all untreated patients showed severe cerebral deterioration and often died at an early age compared to patients with classic PKU. However, these disorders are no longer fatal with proper treatment; thus, the term 'malignant' should not be used (Dudesek et al., 2001).
Animal Model
Sumi-Ichinose et al. (2001) established mice unable to synthesize BH4 by disrupting the Pts gene. Homozygous mice were born almost at the expected mendelian ratio, but died within 48 hours of birth. In the brains of homozygous mutant neonates, levels of biopterin, catecholamines, and serotonin were extremely low. Tyrosine hydroxylase (TH; 191290) activity was severely impaired by BH4 depletion, and TH immunoreactivity was reduced in the nerve terminals, but not in the cell bodies. The catecholaminergic, serotonergic, and nitric oxide (see NOS1, 163731) systems were differentially affected by BH4 starvation and were variably rescued by BH4 administration.
INHERITANCE \- Autosomal recessive GROWTH Other \- Small for gestational age \- Poor feeding in infancy HEAD & NECK Head \- Microcephaly Eyes \- Oculogyric crises Mouth \- Hypersalivation ABDOMEN Gastrointestinal \- Poor sucking \- Swallowing difficulties NEUROLOGIC Central Nervous System \- Delayed development \- Psychomotor retardation \- Mental retardation \- Hypotonia, truncal \- Hypertonia of the extremities \- Hyperreflexia \- Extrapyramidal signs \- Uncoordinated movements \- Ataxia \- Tremor \- Parkinsonism \- Bradykinesia \- Rigidity \- Stiffness \- Dystonia \- Seizures \- Choreoathetosis \- Somnolence \- Disturbed sleep patterns Behavioral Psychiatric Manifestations \- Irritability METABOLIC FEATURES \- Hyperthermia, episodic LABORATORY ABNORMALITIES \- Hyperphenylalaninemia \- Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF \- Increased neopterin in urine and CSF \- Decreased or absent PTS activity MISCELLANEOUS \- Onset in infancy (average 4 months, but may be earlier) \- Variable severity, ranging from central severe to peripheral to transient \- Progressive neurologic deterioration if untreated \- Diurnal fluctuation of neurologic symptoms \- Defect in tetrahydrobiopterin (BH4) synthesis \- Treatment with BH4 is effective \- Neurotransmitter treatment with L-dopa and serotonin or precursors is effective \- Early treatment can reduce neurologic symptoms \- Prevalence in Caucasians is 1 in 1,000,000 \- Prevalence in Taiwan is 1 in 132,000 MOLECULAR BASIS \- Caused by mutation in the 6-@pyruvoyl-tetrahydropterin synthase gene PTS, ( 612719.0001 ) ▲ 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
|
HYPERPHENYLALANINEMIA, BH4-DEFICIENT, A
|
c0751436
| 8,253 |
omim
|
https://www.omim.org/entry/261640
| 2019-09-22T16:23:30 |
{"doid": ["0090106"], "mesh": ["D010661"], "omim": ["261640"], "orphanet": ["238583", "13"], "synonyms": ["Alternative titles", "HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO PTS DEFICIENCY", "6-PYRUVOYL-TETRAHYDROPTERIN SYNTHASE DEFICIENCY", "PTS DEFICIENCY"]}
|
Variegate porphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks with or without the presence of cutaneous lesions.
## Epidemiology
Prevalence is around 1/100,000 in European countries and much higher in South Africa due to a founding effect.
## Clinical description
Generally the disease manifests after puberty and preferentially affects women. In 60% of cases the only sign of the disease are cutaneous lesions that result from photosensitivity (bullous photodermatitis). These lesions predominate in areas exposed to the sun (hands, face) and manifest as bullae that cause differing degrees of pain and that leave scars that are often hyperpigmented. In 20% of cases, patients present with both cutaneous lesions and neuro-visceral attacks. Finally, 20% of patients present with only neuro-visceral attacks. Attacks can persist for several weeks and manifest as intense abdominal pain, and neurological and psychological symptoms. The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. Neurological manifestations can affect the central nervous system as much as the peripheral nervous system and can lead to severe complications such as motor paralysis. The attacks are most commonly triggered by exogenous factors (porphyrinogenic drugs, alcohol, infections, a hypo-calorific diet, stress), and/or endogenous factors (hormonal, linked to menstrual cycle).
## Etiology
Variegate porphyria is caused by a deficiency in protoporphyrinogen oxidase (PPOX; the penultimate enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid, ALA and porphobilinogen, PBG). The enzyme deficiency is due to mutations in the PPOX gene coded for PPOX.
## Diagnostic methods
Diagnosis of acute attacks is based on evidence of elevated concentrations of PBG and ALA in urine and of elevated concentrations of coproporphyrin and, especially, protoporphyrin in stool.
## Differential diagnosis
Differential diagnoses include acute intermittent porphyria and, particularly, porphyria cutanea tarda (see these terms). The presence of a fluorometric peak (626-628 nm) in plasma is pathognomonic and allows a definitive diagnosis of variegate porphyria rather than porphyria cutanea tarda.
## Genetic counseling
Transmission is autosomal dominant. Genetic counseling should be offered to patients and families.
## Management and treatment
Acute attacks should be urgently treated with an injection of human hemin. Management includes both the prevention of attacks (warning against triggering factors) and pain relief (opiates). Phlebotomy and taking chloroquine are rarely effective at treating cutaneous manifestations. Micro-phlebotomy is beneficial for some patients. It is necessary to protect the skin from sources of light.
## Prognosis
With early diagnosis and treatment acute attacks are rarely fatal and the disease is rarely progressive. However, variegate porphyria is a risk factor for the development of hepatocellular carcinoma.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Porphyria variegata
|
c0162532
| 8,254 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79473
| 2021-01-23T17:03:13 |
{"gard": ["7848"], "mesh": ["D046350"], "omim": ["176200"], "umls": ["C0162532"], "icd-10": ["E80.2"], "synonyms": ["Protoporphyrinogen oxidase deficiency", "Variegate porphyria"]}
|
A number sign (#) is used with this entry because of evidence that infantile hypotonia with psychomotor retardation (IHPMR) is caused by homozygous mutation in the CCDC174 gene (616735) on chromosome 3p25.
Clinical Features
Volodarsky et al. (2015) reported 6 children from 2 unrelated families with a similar severe neurodevelopmental disorder. Two Egyptian sibs presented in the first month of life with severe generalized hypotonia requiring a feeding tube and artificial ventilation. The patients, aged 8 and 9 years at the time of the report, had mild psychomotor retardation with delayed speech acquisition. They still required continuous positive airway pressure (CPAP) and gastrostomy feeding. Brain imaging showed dilated lateral ventricles and thin corpus callosum. Four children from a consanguineous Israeli Arab Bedouin family had a similar, but more severe, disorder. Reduced fetal movements were apparent in some cases, and all had severe axial hypotonia and delayed psychomotor development. Brain imaging in 2 patients was normal. Three of the 4 died before 4 months of age, and 1 was alive at age 2 years. Muscle biopsy in the Egyptian sibs did not show evidence of necrosis or increased fibrosis, but electron microscopy showed destruction of myofibrils with no evidence of regeneration. Muscle biopsy in the Arab children showed moderate to severe myopathic changes, increased fibrosis, increased variation in fiber size, small atrophic fibers, and sporadic fibers with internal nuclei. Muscle biopsy of 1 patient showed depletion of RYR1 (180901). Additional features in both families included strabismus due to abducens nerve palsy, cardiac septal defects, and cryptorchidism in the males. Serum creatine kinase was normal in both families.
Inheritance
The transmission pattern of IHPMR in the families reported by Volodarsky et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 6 patients from 2 unrelated families with IHPMR, Volodarsky et al. (2015) identified a homozygous mutation in the CCDC164 gene (616735.0001) that was predicted to extend the protein by 6 additional residues (Ter468TrpextTer6). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in both families. Haplotype analysis suggested a founder effect for the 2 families. Expression of the mutation into ccdc174-null Xenopus oocytes was unable to rescue the neural defect, consistent with a loss of function. Mutant CCDC174 localized normally to the nucleus and was able to interact with EIF4A3 (608546), but overexpression of mutant CCDC174 resulted in rapid and massive apoptosis of cells and aggregation of the mutant protein in the nucleus.
Animal Model
Volodarsky et al. (2015) found that morpholino knockdown of the ccdc174 ortholog in Xenopus oocytes resulted in poor neural fold closure and a reduction in markers for differentiating primary neurons. Survival was also decreased at later embryonic stages. Knockdown embryos showed a sharp reduction in expression of n-tubulin, a marker for differentiating primary neurons, and of hindbrain markers krox20 (129010) and hoxb3 (142966), suggesting a disruption in early neural plate patterning and neuron formation.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Myopathic facies Eyes \- Strabismus \- Abducens nerve palsy Mouth \- Open mouth CARDIOVASCULAR Heart \- Cardiac septal defects RESPIRATORY \- Respiratory insufficiency due to muscle weakness ABDOMEN Gastrointestinal \- Feeding difficulties due to muscle weakness GENITOURINARY External Genitalia (Male) \- Cryptorchidism MUSCLE, SOFT TISSUES \- Hypotonia, neonatal, severe \- Myopathic changes see on muscle biopsy \- Increased fibrosis (in some patients) \- Increased variation in fiber size (in some patients) \- Small atrophic fibers (in some patients) \- Increased internal nuclei (in some patients) \- Myofibril destruction (in some patients) NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Poor speech acquisition \- Thin corpus callosum (in some patients) \- Enlarged ventricles (in some patients) PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements MISCELLANEOUS \- Onset in utero or at birth \- Two unrelated families have been reported (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 174 gene (CCDC174, 616735.0001 ) ▲ 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
|
HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION
|
c4225196
| 8,255 |
omim
|
https://www.omim.org/entry/616816
| 2019-09-22T15:47:49 |
{"omim": ["616816"], "orphanet": ["467176"], "synonyms": []}
|
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Cone dystrophy" – news · newspapers · books · scholar · JSTOR (September 2017)
Cone dystrophy
Fundus of a 34-year-old patient with cone rod dystrophy due to Spinocerebellar Ataxia Type 7 (SCA7). Note that the macular area, and also the mid periphery, are atrophic.
SpecialtyOphthalmology
A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.
## Contents
* 1 Presentation
* 2 Dystrophy of the rods and cones
* 3 Mechanism
* 4 Diagnosis
* 5 Treatment
* 6 Notes
* 7 References
* 8 External links
## Presentation[edit]
The most common symptoms of cone dystrophy are vision loss (age of onset ranging from the late teens to the sixties), sensitivity to bright lights, and poor color vision. Therefore, patients see better at dusk. Visual acuity usually deteriorates gradually, but it can deteriorate rapidly to 20/200; later, in more severe cases, it drops to "counting fingers" vision. Color vision testing using color test plates (HRR series) reveals many errors on both red-green and blue-yellow plates.
## Dystrophy of the rods and cones[edit]
Dystrophy of the light-sensing cells of the eye may also occur in the rods as well, or in both the cones and the rods.
A type of rod-cone dystrophy—where rod function decline is typically earlier or more pronounced than cone dystrophy—has been identified as a relatively common characteristic of Bardet–Biedl Syndrome.[1]
At least one type of autosomal dominant cone-rod dystrophy is caused by mutations in the guanylate cyclase 2D gene (GUCY2D) on chromosome 17.[citation needed]
## Mechanism[edit]
The pathogenesis of cone dystrophy has yet to be elucidated. It appears that the dystrophy is primary, since subjective and objective abnormalities of cone function are found before ophthalmoscopic changes can be seen. However, the retinal pigment epithelium (RPE) rapidly becomes involved, leading to a retinal dystrophy primarily involving the macula. The histological examination of the eyes of one such patient showed that the outer nuclear layer of cones and rods had disappeared completely, whereas the RPE showed pronounced pigment changes. There was also atrophy of the temporal disc.
## Diagnosis[edit]
The fundus exam via ophthalmoscopy is essentially normal early on in cone dystrophy, and definite macular changes usually occur well after visual loss. Fluorescein angiography (FA) is a useful adjunct in the workup of someone suspected to have cone dystrophy, as it may detect early changes in the retina that are too subtle to be seen by ophthalmoscope. For example, FA may reveal areas of hyperfluorescence, indicating that the RPE has lost some of its integrity, allowing the underlying fluorescence from the choroid to be more visible. These early changes are usually not detected during the ophthalmoscopic exam.
The most common type of macular lesion seen during ophthalmoscopic examination has a bull’s-eye appearance and consists of a doughnut-like zone of atrophic pigment epithelium surrounding a central darker area. In another, less frequent form of cone dystrophy there is rather diffuse atrophy of the posterior pole with spotty pigment clumping in the macular area. Rarely, atrophy of the choriocapillaris and larger choroidal vessels is seen in patients at an early stage. The inclusion of fluorescein angiography in the workup of these patients is important since it can help detect many of these characteristic ophthalmoscopic features. In addition to the retinal findings, temporal pallor of the optic disc is commonly observed. As expected, visual field testing in cone dystrophy usually reveals a central scotoma. In cases with the typical bull’s-eye appearance, there is often relative central sparing.[citation needed]
Because of the wide spectrum of fundus changes and the difficulty in making the diagnosis in the early stages, electroretinography (ERG) remains the best test for making the diagnosis. Abnormal cone function on the ERG is indicated by a reduced single-flash and flicker response when the test is carried out in a well-lit room (photopic ERG). The relative sparing of rod function in cone dystrophy is evidenced by a normal scotopic ERG, i.e. when the test is carried out in the dark. In more severe or longer standing cases, the dystrophy involves a greater proportion of rods with resultant subnormal scotopic records. Since cone dystrophy is hereditary and can be asymptomatic early on in the disease process, ERG is an invaluable tool in the early diagnosis of patients with positive family histories. Cone dystrophy in general usually occurs sporadically. Hereditary forms are usually autosomal dominant, and instances of autosomal recessive and X-linked inheritance also occur.
In the differential diagnosis, other macular dystrophies as well as the hereditary optic atrophies must be considered. Fluorescent angiography, ERG, and color vision tests are important tools to help facilitate diagnosis in early stages.[citation needed]
## Treatment[edit]
Though there is no treatment for cone dystrophy, certain supplements may help in delaying the progression of the disease.
The beta-carotenoids, lutein and zeaxanthin, have been evidenced to reduce the risk of developing age-related macular degeneration (AMD),[2] and may therefore provide similar benefits[according to whom?] to cone dystrophy sufferers.[citation needed]
Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early AMD, and in conjunction with low glycemic index foods, with reduced progression of advanced AMD,[3] and may therefore delay the progression of cone dystrophy.
Dr. Randall Walker, who has a variation of the condition himself, invented a software to enable low vision people to read with greater ease. <ref> url= https://www.bizjournals.com/twincities/print-edition/2014/06/06/made-at-mayo-mayo-professor-doubles-as-founder-of.html <ref>
## Notes[edit]
1. ^ Beales P, Elcioglu N, Woolf A, Parker D, Flinter F (1 June 1999). "New criteria for improved diagnosis of Bardet–Biedl syndrome: results of a population survey". J. Med. Genet. 36 (6): 437–46. doi:10.1136/jmg.36.6.437 (inactive 2021-01-17). PMC 1734378. PMID 10874630. Archived from the original on 2008-03-14. Retrieved 2007-10-11.CS1 maint: DOI inactive as of January 2021 (link)
2. ^ Carpentier S, Knaus M, Suh M (2009). "Associations between lutein, zeaxanthin, and age-related macular degeneration: An overview". Critical Reviews in Food Science and Nutrition. 49 (4): 313–326. doi:10.1080/10408390802066979. PMID 19234943. S2CID 23524407. "Abstract doesn't include conclusion"
3. ^ Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A (June 2009). "Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?". Br J Ophthalmol. 93 (9): 1241–6. doi:10.1136/bjo.2008.143412. PMC 3033729. PMID 19508997. "Conclusions: The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD."
## References[edit]
* Stephen J. Ryan et al., Retina, 3rd ed. (C.V. Mosby, 2001) ISBN 0-323-00804-6
* Stephen J. Ryan et al., Retina, 4th ed. (C.V. Mosby, 2005) ISBN 0-323-02598-6
* Carpentier S, Knaus M, Suh M (April 2009). "Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview". Crit Rev Food Sci Nutr. 49 (4): 313–26. doi:10.1080/10408390802066979. PMID 19234943. S2CID 23524407.CS1 maint: multiple names: authors list (link) "Abstract doesn't include conclusion"
* Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A (September 2009). "Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?". Br J Ophthalmol. 93 (9): 1241–6. doi:10.1136/bjo.2008.143412. PMC 3033729. PMID 19508997.CS1 maint: multiple names: authors list (link) "Conclusions: The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD."
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing 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 dystrophy
|
c1867326
| 8,256 |
wikipedia
|
https://en.wikipedia.org/wiki/Cone_dystrophy
| 2021-01-18T18:55:10 |
{"gard": ["11897"], "mesh": ["C566719"], "umls": ["C1867326"], "icd-10": ["H35.5"], "orphanet": ["1871"], "wikidata": ["Q147270"]}
|
## Clinical Features
Sener (1994) described a female child who had facial dysmorphism with hypodontia, dental occlusion, and buccal frenula. In addition she had thin hair and dystrophic nails. Her development was normal until the age of 5 years, and she subsequently developed mild developmental delay. An MRI scan showed multiple cysts of curvilinear configuration, representing extremely dilated Virchow-Robin spaces (the perivascular spaces lined by ependymal/leptomeningeal cells). Sener (1994) described this as a distinct neurocutaneous syndrome.
Lynch et al. (2000) described 2 children who they believed had the same condition as that described by Sener (1994). Both children were male. Case 1 had edema of the neck at birth with a large anterior fontanel, a short penis with large scrotum, and anteriorly placed anus. Cranial ultrasound showed partial agenesis of the corpus callosum, and renal ultrasound showed mild dilatation of the pelvicalyceal system. Bilateral inguinal herniae were repaired at 4 months of age. Ophthalmologic examination showed hypoplastic left disc and a small coloboma of the right disc. He had hypertelorism with a wide mouth, long, smooth philtrum, and small posteriorly rotated ears. His hair was coarse and brittle. The teeth were irregular and pointed. Karyotype, Skeletal survey, and metabolic investigations were normal. Case 2 had similar dysmorphic features but in addition had a midline cleft of the upper alveolar margin and 2 neonatal teeth. Both patients were developmentally delayed. MRI scan in both children showed multiple cystic areas within the white matter radiating from the ventricles into oval lobes with sparing of the basal ganglia, brainstem, and corpus callosum. Lynch et al. (2000) observed that the distribution of cystic changes in the MRI scan of their cases mirrored the perivascular distribution of the Virchow-Robin spaces. They noted that similar MRI findings had been described in the mucopolysaccharidoses (see 607014); however, screening of urinary amino acids was negative in their cases.
Winter (2001) reviewed several reports that are now listed in this entry and in 243310. He noted considerable overlap between the cases and suggested that they represent a syndrome, called the cerebrofrontofacial syndrome, that is comprised of 3 types based on brain MRI findings. The brain scans in type 1 are characterized by periventricular nodular heterotopia. In type 2, there are multiple cystic areas in the white matter radiating at right angles to the ventricles. These are interpreted as being dilated Virchow-Robin spaces. In type 3, there is no periventricular nodular heterotopia or cystic areas of the brain. Verloes et al. (2015) suggested that types 1 and 3 are the same as Baraitser-Winter syndrome (see 243310); type 2 corresponds with Sener syndrome.
INHERITANCE \- Isolated cases HEAD & NECK Head \- Large anterior fontanelle Face \- Smooth philtrum Ears \- Small ears \- Posteriorly rotated ears Eyes \- Hyperopic astigmatism \- Entropion \- Hypertelorism Mouth \- Wide mouth \- High-arched palate Teeth \- Neonatal teeth \- Delayed eruption of secondary teeth \- Hypodontia CARDIOVASCULAR Vascular \- Patent ductus arteriosus ABDOMEN External Features \- Umbilical hernia Gastrointestinal \- Anteriorly placed anus \- Chronic diarrhea GENITOURINARY External Genitalia (Male) \- Short penis \- Inguinal hernia SKIN, NAILS, & HAIR Skin \- Eczema Hair \- Coarse hair NEUROLOGIC Central Nervous System \- Developmental delay \- Hypoplastic corpus callosum \- Dilated Virchow-Robin spaces PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios ▲ 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
|
SENER SYNDROME
|
c1853616
| 8,257 |
omim
|
https://www.omim.org/entry/606156
| 2019-09-22T16:10:37 |
{"mesh": ["C537579"], "omim": ["606156"], "synonyms": ["Alternative titles", "FRONTONASAL DYSPLASIA AND DILATED VIRCHOW-ROBIN SPACES"]}
|
Paramyotonia congenita is an inherited condition that affects muscles used for movement (skeletal muscles), mainly in the face, neck, arms, and hands. Symptoms begin in infancy or early childhood and include episodes of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally and lead to muscle weakness. Symptoms in paramyotonia congenita worsen during exposure to cold temperatures, and unlike many other forms of myotonia, worsen with exercise and repeated movements. This condition is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant pattern.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Paramyotonia congenita
|
c0221055
| 8,258 |
gard
|
https://rarediseases.info.nih.gov/diseases/7325/paramyotonia-congenita
| 2021-01-18T17:58:26 |
{"mesh": ["D020967"], "omim": ["168300"], "orphanet": ["684"], "synonyms": ["PMC", "Paramyotonia congenita of Von Eulenburg", "Paralysis periodica paramyotonica", "Eulenburg disease", "Myotonia congenita intermittens", "Von Eulenburg paramyotonia congenita"]}
|
A number sign (#) is used with this entry because of evidence that thyroid dyshormonogenesis-4 (TDH4) is caused by homozygous mutation in the iodotyrosine deiodinase gene (IYD; 612025) on chromosome 6q25.
For a general phenotypic description and a discussion of genetic heterogeneity of thyroid dyshormonogenesis, see TDH1 (274400).
Clinical Features
The deiodinases are a group of membrane bound, NADPH-dependent, FAD-enhanced isoenzymes found in the thyroid, kidney, liver, and other organs. Patients with this defect lack the ability to deiodinate radiolabeled monoiodotyrosine (MIT) and diiodotyrosine (DIT). This results in continuous urinary loss of iodine and tyrosine from the body. Most of the earlier reported patients had severe congenital hypothyroidism. In a classic study, Hutchison and McGirr (1954, 1956) described this disorder in inbred, itinerant tinkers from western Scotland. Werdnig-Hoffman disease occurred also in this family, apparently as an independently inherited disorder. Kusakabe and Miyake (1963) described a mother and daughter plus 2 other unrelated individuals who showed defective peripheral iodotyrosine deiodination but essentially normal in vitro thyroidal activity. Kusakabe and Miyake (1964) reported 3 affected sisters, from a sibship of 7 born to healthy, first-cousin parents, whose thyroidal tissue lacked deiodinase activity, but whose peripheral tissues deiodinated radiolabeled MIT and DIT normally. The patients with these limited tissue defects had normal growth and development. Ismail-Beigi and Rahimifar (1977) found a mild variant of the defect in 3 children born to unaffected first cousins.
Afink et al. (2008) described a highly consanguineous Belgian Moroccan family segregating an apparently recessive phenotype of goiter, delayed psychomotor development, and stunted growth, which first came to medical attention in 1967. The 5-year-old female proband showed excretion of 50 to 70% of an administered dose of radiolabeled DIT, compared to controls who only secreted 15 to 20%, consistent with a diagnosis of deiodinase deficiency. The proband went on to have 5 children, 1 of whom was born with goiter and diagnosed with hypothyroidism due to dyshormonogenesis.
Molecular Genetics
In 4 patients from 3 unrelated consanguineous families with hypothyroidism and biochemical features or a clinical history suggestive of an iodotyrosine deiodinase defect, Moreno et al. (2008) identified homozygosity for 3 different mutations in the iodotyrosine deiodinase (IYD) gene (612025.0001-612025.0003, respectively). Two of the patients were sisters whose consanguineous parents were members of the group of Scottish traveling families previously described by Hutchison and McGirr (1954, 1956).
Afink et al. (2008) analyzed the IYD gene in a consanguineous Belgian Moroccan family segregating apparently recessive hypothyroidism and goiter consistent with deiodinase deficiency, and identified homozygosity for a missense mutation (612025.0003) in the proband and her affected daughter; 4 clinically unaffected offspring were heterozygous for the mutation. Six years after DNA testing, a heterozygous 14-year-old son developed nonautoimmune goiter and hypothyroidism, indicating dominant inheritance with incomplete penetrance, which Afink et al. (2008) noted had been previously suggested in some families (Codaccioni et al., 1970). The mutation was also found in 1 of 100 control alleles, suggesting that it might represent a functional SNP.
History
The hypothyroidism in this disorder results not from dyshormonogenesis, but from simple iodine depletion (Stanbury, 1978). This has been well demonstrated by Codaccioni et al. (1970), who maintained euthyroidism in 5 patients with the complete defect by giving supplemental iodide alone. Rochiccioli and Dutau (1974) showed reduced deiodination of radiolabeled DIT after loading obligated carriers with cold DIT, thereby making heterozygote detection possible.
INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation HEAD & NECK Neck \- Goiter NEUROLOGIC Central Nervous System \- Mental retardation (if untreated in infancy) ENDOCRINE FEATURES \- Hypothyroidism LABORATORY ABNORMALITIES \- Low T4 \- Low T3 \- Rapid high RAI (radioactive iodine) uptake and turnover \- Iodotyrosine deiodinase deficiency \- Continuous urinary iodine loss \- Tyrosine loss \- Iodine depletion MOLECULAR BASIS \- Caused by mutation in the iodotyrosine deiodinase gene (IYD, 612025.0001 ) ▲ 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
|
THYROID DYSHORMONOGENESIS 4
|
c0342195
| 8,259 |
omim
|
https://www.omim.org/entry/274800
| 2019-09-22T16:21:40 |
{"mesh": ["C562770"], "omim": ["274800", "274400"], "orphanet": ["95716"], "synonyms": ["DEIODINASE DEFICIENCY", "HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 4", "Alternative titles", "IODOTYROSINE DEHALOGENASE DEFICIENCY", "THYROID HORMONOGENESIS, GENETIC DEFECT IN, 4", "Thyroid dyshormonogenesis"]}
|
## Clinical Features
In an extensive Brazilian kindred of Portuguese extraction, Kinton et al. (2002) observed a familial epilepsy syndrome, which they designated partial epilepsy with pericentral spikes (PEPS). Affected members in the family reported by Kinton et al. (2002) manifested a variety of seizure types, including hemiclonic, hemitonic, generalized tonic-clonic, simple partial (stereotyped episodes of epigastric pain), and complex partial seizures consistent with temporal lobe epilepsy. The syndrome was benign, either requiring no treatment or responding to a single antiepileptic medication. Seizure onset was in the first or second decade of life, with seizures in individuals up to the age of 71 years and documented encephalogram changes up to the age of 30 years. A key feature of PEPS was a characteristic encephalogram abnormality of spikes or sharp waves in the pericentral region (centroparietal, centrofrontal, or centrotemporal). The distinctive encephalogram abnormality of pericentral spikes united the several seizure types into a discrete epilepsy syndrome. The inherited nature of the syndrome could be overlooked because of the variability in penetrance and seizure types among affected family members.
Inheritance
The pedigree pattern in the family with PEPS reported by Kinton et al. (2002) was consistent with autosomal dominant inheritance, with vertical and male-to-male transmission. There was evidence of incomplete penetrance, both for the EEG trait and epilepsy, with obligate gene carriers remaining unaffected up to ages 66 and 70 years, respectively.
Mapping
By linkage studies, Kinton et al. (2002) mapped the epilepsy in the Brazilian family to 4p15 with a maximum lod score of 3.3 at D4S2311. Haplotype analysis confirmed the boundaries of the critical region. Homozygosity for the haplotype was not associated with a more severe phenotype.
Molecular Genetics
For discussion of a possible role of variation in the METTL19 gene in PEPS, see 614309.0001.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EPILEPSY, PARTIAL, WITH PERICENTRAL SPIKES
|
c1846609
| 8,260 |
omim
|
https://www.omim.org/entry/607221
| 2019-09-22T16:09:31 |
{"mesh": ["C564605"], "omim": ["607221"], "synonyms": ["Alternative titles", "EPPS"]}
|
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder characterized by adult-onset parkinsonism that is frequently accompanied by focal dystonia, which becomes generalized over time, and that has a highly variable clinical course.
## Epidemiology
Over 500 cases of XDP have been reported in the literature to date, all occurring in the Philippines (Panay Island). The estimated prevalence in the Philippines is 1/322,000 and in the Province of Capiz it is at its highest with a prevalence of 1/4,000 in the male population.
## Clinical description
XDP affects mainly males, most female carriers are asymptomatic. The disease typically presents in adulthood (mean: 39 years) with either focal dystonia or, more commonly, parkinsonism. Focal dystonia affects mainly the jaw, neck, eyes and trunk, but also rarely the limbs, pharynx, larynx and tongue, leading to various manifestations such as difficulty with jaw opening and closing, blepharospasm, involuntary tongue protrusion, difficulty swallowing, retrocollis, trunk hyperextension, leg spasms, foot flexion, and foot inversion. Within 2-5 years after onset, 50% of patients have generalized dystonia. Parkinsonism manifests with bradykinesia, rigidity, resting tremor, shuffling gait and postural instability, which may be severe and can lead to walking impairment and frequent stumbling. Less common findings include sensory tricks, myoclonus, chorea and myorhythmia. In those with pure parkinsonism, the disease progresses slowly and is usually non-disabling. Most who develop orobuccolingual and cervical dystonia suffer from lethal complications such as infections, aspiration pneumonia and laryngeal stridor, leading to premature death. Mean duration of illness is 13-16 years.
## Etiology
XDP is due to mutations in the TAF1 gene (Xq13.1) encoding the TAF1 RNA polymerase II, TATA box-binding protein-associated factor, 250kDa.
## Diagnostic methods
Diagnosis is based on clinical and neuroimaging findings (of postsynaptic striatal and presynaptic nigrostriatal involvement), as well as having a positive family history compatible with X-linked inheritance and maternal Panay Island ancestral roots. MRI usually shows no abnormalities. Molecular genetic testing can confirm the diagnosis by identifying a TAF1 mutation. Preliminary results from a pilot study indicate olfactory dysfunction in XDP, therefore olfactory testing may also support diagnosis.
## Differential diagnosis
Differential diagnoses include Parkinson's disease, hereditary essential tremor, dopa-responsive dystonia and Parkinson-plus syndromes.
## Antenatal diagnosis
Prenatal diagnosis is possible in families with a known TAF1 mutation.
## Genetic counseling
XDP is inherited in an X-linked recessive manner and genetic counseling is recommended. Males with XDP pass the mutation to all of their daughters and none of their sons, whereas female carriers have a 50% risk of passing the mutation to their offspring. Rare de novo mutations have been reported.
## Management and treatment
There is no cure for XDP. Treatment involves the use of pharmacological agents and offers only temporary or partial relief. In the early stages of dystonia, benzodiazepines and anticholinergic agents may be effective, especially in combination. Botulinum toxin injections may relieve focal dystonia. Tetrabenazine and zolpidem can improve dystonia once it becomes generalized or multifocal. Those with pure parkinsonism may be responsive to levodopa. Deep brain stimulation has shown promise in a few cases with advanced disease refractory to medication. Periodic swallowing evaluation is recommended, especially in those with dysphagia. Physical therapy may be helpful. Psychological counseling should be offered to patients and their families.
## Prognosis
Prognosis is phenotype-dependent. Those with pure parkinsonism have the best prognosis, while those with a combination of parkinsonism followed by the development of orobuccolingual and cervical dystonia, 1-2 years after disease onset, have the worst prognosis, usually becoming bedridden with a reduced life expectancy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing 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 dystonia-parkinsonism
|
c1839130
| 8,261 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=53351
| 2021-01-23T17:37:03 |
{"gard": ["10533"], "mesh": ["C564048"], "omim": ["314250"], "umls": ["C1839130"], "icd-10": ["G24.1"], "synonyms": ["DYT3", "Lubag", "Lubag syndrome", "XDP"]}
|
Not to be confused with Marasmius.
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: "Marasmus" – news · newspapers · books · scholar · JSTOR (January 2017) (Learn how and when to remove this template message)
Marasmus
Child with Marasmus in India, 1972
SpecialtyCritical care medicine
Marasmus is a form of severe malnutrition characterized by energy deficiency. It can occur in anyone with severe malnutrition but usually occurs in children.[1] Body weight is reduced to less than 62% of the normal (expected) body weight for the age.[2] Marasmus occurrence increases prior to age 1, whereas kwashiorkor occurrence increases after 18 months. It can be distinguished from kwashiorkor in that kwashiorkor is protein deficiency with adequate energy intake whereas marasmus is inadequate energy intake in all forms, including protein. This clear-cut separation of marasmus and kwashiorkor is however not always clinically evident as kwashiorkor is often seen in a context of insufficient caloric intake, and mixed clinical pictures, called marasmic kwashiorkor, are possible. Protein wasting in kwashiorkor generally leads to edema and ascites, while muscular wasting and loss of subcutaneous fat are the main clinical signs of marasmus.[3]
The prognosis is better than it is for kwashiorkor[4] but half of severely malnourished children die due to unavailability of adequate treatment.[citation needed]
The word “marasmus” comes from the Greek μαρασμός marasmos ("withering").
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Treatment
* 4 Epidemiology
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
Buchenwald inmates, 16 April 1945 when camp was liberated
Marasmus is commonly represented by a shrunken, wasted appearance, loss of muscle mass and subcutaneous fat mass.[5] Buttocks and upper limb muscle groups are usually more affected than others. Edema is not a sign of marasmus and is present in only kwashiorkor and marasmic kwashiorkor. Other symptoms of marasmus include unusual body temperature (hypothermia, pyrexia); anemia; dehydration (as characterized with consistent thirst and shrunken eyes); hypovolemic shock (weak radial pulse; cold extremities; decreased consciousness); tachypnea (pneumonia, heart failure); abdominal manifestations (distension, decreased or metallic bowel sounds; large or small liver; blood or mucus in the stools), ocular manifestations (corneal lesions associated with vitamin A deficiency); dermal manifestations (evidence of infection, purpura, and ear, nose, and throat symptoms (otitis, rhinitis).[citation needed] Dry skin and brittle hair are also symptoms of marasmus. Marasmus can also make children short-tempered and irritable.[1]
## Causes[edit]
Marasmus is caused by the following factors:
* Maternal malnutrition
* Maternal anemia
* Parental ignorance
* Poverty
* Pathological conditions in a baby (e.g., diarrhea)
* Pneumonia
* Cyanotic heart diseases
* Malaria
* Necrotizing enterocolitis
* Pyloric stenosis
* Lactose intolerance
* Intussusception
* Meningitis
* Anorexia Nervosa
## Treatment[edit]
Both the causes and complications of the disorder must be treated, including infections, dehydration, and circulation disorders, which are frequently lethal and lead to high mortality if ignored.[citation needed] Initially, the child is fed dried skim milk that has been mixed with boiled water. Once the child tolerates the milk, a vegetable mix can be added including sesame, casein, and sugar.[6] Refeeding must be done slowly to avoid refeeding syndrome. Once children start to recover, they should have more balanced diets which meet their nutritional needs. Children with marasmus commonly develop infections and are consequently treated with antibiotics or other medications.[7] Ultimately, marasmus can progress to the point of no return when the body's ability for protein synthesis is lost. At this point, attempts to correct the disorder by giving food or protein are futile.[citation needed]
## Epidemiology[edit]
This section needs expansion. You can help by adding to it. (July 2016)
United States
In the United States, marasmus is rarely seen, especially in children. In 1995, there were only 228 deaths caused by marasmus in the U.S., of which only 3 were children. In 2016, the prevalence of marasmus in the United States was 0.5%. Prevalence is higher in hospitalized children, especially ones with chronic illnesses, however an exact incidence of nonfatal marasmus is not known. This is due to marasmus not being reported as an admission or discharge diagnosis.[8]
International
There are multiple forms of malnutrition and roughly 1/3 of the world’s population is currently experiencing one or more of them. There are around 50 million children less than 5 years old who have protein-energy malnutrition. Of the malnourished children population in the world, 80% live in Asia, 15% in Africa, and 5% in Latin America. It is estimated that the prevalence of acute malnutrition in Germany, France, the United Kingdom, and the United States to be 6.1-14%. In Turkey, the prevalence is as high as 32%.[8]
Race
There is no evident racial predisposition that correlates to malnutrition. Rather, there is a strong association with the geographic distribution of poverty.[9]
Age
Marasmus is more commonly seen in children under the age of 5 due to that age range being characterized as one that has an increase in energy need and susceptibility to viral and bacterial infections.[10] The World Health Organization also identifies the elderly as another population that is vulnerable to malnutrition. Because their nutritional requirement is not well defined, attempts to provide them with the necessary nutrition becomes difficult.[11]
There exists screening tools and tests that can be used to help identify signs and symptoms of malnutrition in older adults. The Malnutrition Screening Tool (MST) is a validated malnutrition screening tool that is primarily used in the residential aged care facility or for adults in the inpatient/outpatient hospital setting. It includes parameters such as weight loss and appetite.[12]
Disability-adjusted life year for protein-energy malnutrition per 100,000 inhabitants in 2002.[13]
no data
less than 10
10–100
100–200
200–300
300–400
400–500
500–600
600–700
700–800
800–1000
1000–1350
more than 1350
Persons in prisons, concentration camps, and refugee camps are affected more often due to poor nutrition.
## See also[edit]
* Starvation
* Cachexia
* Emaciation
* Kwashiorkor
## References[edit]
1. ^ a b "What You Should Know About Marasmus". Healthline.
2. ^ Appleton & Vanbergen, Metabolism and Nutrition, Medicine Crash Course 4th ed. Moseby (London: 2013) p.130
3. ^ Müller, Olaf; Krawinkel, Michael (2005-08-02). "Malnutrition and health in developing countries". CMAJ : Canadian Medical Association Journal. 173 (3): 279–286. doi:10.1503/cmaj.050342. ISSN 0820-3946. PMC 1180662. PMID 16076825.
4. ^ Badaloo AV, Forrester T, Reid M, Jahoor F (June 2006). "Lipid kinetic differences between children with kwashiorkor and those with marasmus". Am. J. Clin. Nutr. 83 (6): 1283–8. doi:10.1093/ajcn/83.6.1283. PMID 16762938.
5. ^ Rabinowitz, Simon. "MD, PhD, FAAP". Emedicine Medscape. Medscape. p. 28. Retrieved 29 January 2015.
6. ^ "What You Should Know About Marasmus".
7. ^ "What You Should Know About Marasmus". Healthline.
8. ^ a b "Marasmus: Background, Pathophysiology, Body Composition". 2019-02-02. Cite journal requires `|journal=` (help)
9. ^ Stephens, Janna D.; Althouse, Andrew; Tan, Alai; Melnyk, Bernadette Mazurek (2017). "The Role of Race and Gender in Nutrition Habits and Self-Efficacy: Results from the Young Adult Weight Loss Study". Journal of Obesity. 2017: 5980698. doi:10.1155/2017/5980698. ISSN 2090-0708. PMC 5406727. PMID 28491474.
10. ^ Katona-Apte, Judit; Katona, Peter (2008-05-15). "The Interaction between Nutrition and Infection". Clinical Infectious Diseases. 46 (10): 1582–1588. doi:10.1086/587658. ISSN 1058-4838. PMID 18419494.
11. ^ "WHO | Nutrition for older persons". WHO. Retrieved 2019-08-07.
12. ^ "Malnutrition Screening and Assessment Tools". NCOA. 2017-01-20. Retrieved 2019-08-07.
13. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.
## External links[edit]
Classification
D
* ICD-10: E41-E42
* ICD-9-CM: 261
* MeSH: D011502
* DiseasesDB: 7826
External resources
* eMedicine: ped/164
* v
* t
* e
Malnutrition
Protein-energy
malnutrition
* Kwashiorkor
* Marasmus
* Catabolysis
Vitamin deficiency
B vitamins
* B1
* Beriberi
* Wernicke–Korsakoff syndrome
* Wernicke's encephalopathy
* Korsakoff's syndrome
* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
* Potassium
* Magnesium
* Calcium
* Iron
* Zinc
* Manganese
* Copper
* Iodine
* Chromium
* Molybdenum
* Selenium
* Keshan disease
Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
* Weight loss
* Cachexia
* Underweight
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Marasmus
|
c0086588
| 8,262 |
wikipedia
|
https://en.wikipedia.org/wiki/Marasmus
| 2021-01-18T18:34:16 |
{"mesh": ["D011502"], "umls": ["C0086588"], "wikidata": ["Q582904"]}
|
A number sign (#) is used with this entry because of evidence that short-rib thoracic dysplasia-6 with or without polydactyly (SRTD6) is caused by homozygous mutation in the NEK1 gene (604588) on chromosome 4q33.
There is also evidence that SRTD can be caused by digenic biallelic mutation in the NEK1 and DYNC2H1 (603297) genes.
Description
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).
There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330).
For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Clinical Features
Majewski et al. (1971) reported 4 cases with a syndrome characterized by short ribs and limbs, median cleft lip, pre- and postaxial polysyndactyly, genital abnormalities, and anomalies of epiglottis and viscera. Death occurred perinatally in all. Majewski et al. (1971) identified 32 nearly identical or similar cases from the literature.
Spranger et al. (1974) reported a similar patient (case 1) whose sib may have died of the same condition, which they referred to as Majewski type short rib-polydactyly (SRP) syndrome. They noted that polycystic kidneys occur with this condition as well as with Meckel syndrome (249000). Spranger et al. (1974) stated that the most distinctive finding in the Majewski type of SRP syndrome is disproportionate shortening of the tibia. The radiologic appearance of the pelvis is normal and the metaphyseal margins of the tubular bones are regular.
Motegi et al. (1979) appear to have reported the first confirmed instance of Majewski syndrome in sibs (2 brothers).
Chen et al. (1980) reported a case with consanguineous parents. Microscopically, cartilage showed markedly stunted and disorganized endochondral ossification. Extraskeletal manifestations were hydrops, cleft lip, malformed larynx with hypoplastic epiglottis, pulmonary hypoplasia, glomerular and renal tubular cysts, ambiguous genitalia, pachygyria, and small cerebellar vermis.
Cooper and Hall (1982) reported 3 cases and compared them with 5 other fully documented cases. Two were sibs and 2 previously born children in this family had been affected also; all 4 were male. One case was the offspring of first-cousin Pakistani parents. The authors knew of other cases of the Majewski type of SRPS in Pakistani immigrant families in England. Central harelip and cleft palate were consistent features. The striking oval configuration of the tibias was noted.
Silengo et al. (1987) presented 2 patients who they suggested lent support to the idea that the Mohr (252100) and the Majewski syndromes are mild and severe expressions, respectively, of the same autosomal recessive disorder. The 2 patients had features typical of Mohr syndrome but, in addition, had laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet typical of Majewski syndrome. In the latter condition, the oral/facial findings are almost identical to those of the Mohr syndrome. Franceschini et al. (1995) reported on a patient with manifestations typical of Mohr syndrome and of the short rib-polydactyly syndromes. Neri et al. (1995) suggested that this group of disorders, which they referred to as oral-facial-skeletal syndromes, may turn out to be a family of disorders such as the achondroplasia/craniosynostosis syndromes which had shortly before been traced to mutations in the fibroblast growth factor receptor genes and the achondrogenesis/SED congenita/Stickler complex due to mutation in collagen type II and XI genes.
Thiel et al. (2011) investigated 3 probands, including 2 fetuses and an infant who died 1 hour after birth, with SRPS type II (Majewski) from 3 independent families: 2 consanguineous families of Turkish and Bedouin origin, respectively, and 1 nonconsanguineous family of German origin. All affected individuals had a narrow thorax with hypoplastic lungs, extreme polysyndactyly, disproportionate dwarfism, and median cleft lip and palate. One presented with a ventriculoseptal defect and cystic kidneys. The radiographic hallmarks of all probands included shortened and horizontal ribs, squared scapulae and elevated clavicles with lateral kinking, normal spine and pelvis configuration, and shortening of the bones of all 4 extremities, with extreme reduction of tibial bone length.
### Clinical Variability
McInerney-Leo et al. (2015) reported a 3-year-old girl from the British Isles (patient SKDP-126.3) who exhibited short stature, hyperopia, microform cleft lip, pectus carinatum, narrow thorax with bifurcated ribs, mesomelic shortening of the limbs with significantly short tibiae, brachydactyly, and hypermobile joints. The child also showed gross motor and speech delays, and had macrocephaly that was believed to be secondary to hydrocephalus. She had no renal or cardiac anomalies. The tentative diagnosis was Jeune asphyxiating thoracic dystrophy versus Sensenbrenner syndrome.
Wang et al. (2017) reported a 12.5-year-old Caucasian boy who was considered healthy until age 7 years, when his vision deteriorated abruptly and he was diagnosed with hyperopia, astigmatism, and neuroretinal degeneration. Electroretinography (ERG) at age 11 years showed severe generalized retinal dystrophy. Skeletal dysplasia was diagnosed at age 8 years, when narrow thorax and hyperflexible finger joints were observed. Skeletal survey revealed narrow thorax with short ribs, mild platyspondyly with rounded vertebral bodies, underdeveloped lower pelvis, sclerotic proximal femoral metaphyses and mild metaphyseal broadening of the distal femora and proximal tibia. Echocardiography showed mild insufficiency of bicuspid and tricuspid valves. Laboratory tests including hepatic and renal evaluation were normal. The patient was given a clinical diagnosis of axial spondylometaphyseal dysplasia.
Cytogenetics
Urioste et al. (1994) described an apparently balanced pericentric inversion of chromosome 4 in a newborn infant with clinical and radiologic manifestations of a short rib-polydactyly syndrome. Central cleft upper lip and hamartomatous lesions of the tongue as well as the polydactyly were illustrated. Some manifestations were those of the Majewski type of SRPS, whereas others were those of the Beemer-Langer type (269860). The full clinical pattern was difficult to fit into any of the specific types of SRPS; the clinical findings underscored the considerable overlap of the several types. The mother, who was asymptomatic, had the same (or seemingly same) pericentric inversion of one chromosome 4. Maternal features included complete situs inversus, an anomaly that has been described in the Saldino-Noonan, Verma-Naumoff, and Beemer-Langer types of SRPS, but apparently not in the Majewski type. Urioste et al. (1994) raised the question of whether a gene for SRPS is located at either 4q13 or 4p16, the location of the breakpoints in creation of the pericentric inversion. They suspected 4q13, rather than 4p16, because rearrangements on 4p16 have been described rather frequently and the manifestations have been of a type not shared by the patient they described. In a later note, Urioste et al. (1994) raised the question of the syndrome being due to disruption of a gene in the 4p16 region where achondroplasia, hypochondroplasia, thanatophoric dysplasia, and Ellis-van Creveld syndrome map.
Mapping
By genomewide linkage and homozygosity mapping in 2 consanguineous families segregating SRPS type II, Thiel et al. (2011) mapped the disorder to chromosome 4q32.1-q34.3 (maximum hlod of 2.95).
Molecular Genetics
Thiel et al. (2011) considered the NEK1 gene, located within the SRPS type II locus region, as a likely candidate for the disorder because mutant mice homozygous for the orthologous gene show polycystic kidney disease, craniofacial anomalies, and growth reduction. By sequencing of the NEK1 gene in the probands from 2 consanguineous families, they identified homozygosity for different mutations in each (604588.0001-604588.0002). In the proband from a nonconsanguineous family, they identified heterozygosity for an insertion mutation in the NEK1 gene (604588.0003) and heterozygosity for a missense mutation in the DYNC2H1 gene (603297.0016); no second mutation was found in either gene, and each parent was heterozygous for one of the mutations. Thiel et al. (2011) found that absence of functional full-length NEK1 severely reduces cilia number and alters cilia morphology in vivo.
El Hokayem et al. (2012) analyzed the NEK1 gene in 11 unrelated cases of SRPS type II, all of which were either terminated pregnancies or cases of neonatal death, and identified 4 homozygous mutations in 4 cases (see, e.g., 604588.0001 and 604588.0004). Compound heterozygous mutations in the DYNC2H1 gene (see, e.g., 603297.0017-603297.0020) were identified in 4 cases (see SRTD3; 613091); in the remaining 3 cases, no mutations were found in either gene, suggesting further genetic heterogeneity.
In a 3-year-old British girl with SRTD, McInerney-Leo et al. (2015) performed whole-exome sequencing and identified compound heterozygosity for mutations in the NEK1 gene: a splice site mutation (604588.0009) and a missense mutation (P172S; 604588.0010), neither of which was found in internal or public variant databases. Heterozygosity for a missense mutation in another SRTD-associated gene was also detected in this patient, an H297Q substitution in the WDR60 gene (615462), and the authors noted that this variant might modify the SRTD phenotype.
In a 12.5-year-old boy with severe retinal dystrophy, narrow thorax, short ribs, mild platyspondyly, and mild metaphyseal changes in the long bones, who had been clinically diagnosed with axial spondylometaphyseal dysplasia (see 602271) but was negative for mutation in the C21ORF2 gene (603191), Wang et al. (2017) performed whole-exome sequencing and identified compound heterozygosity for a nonsense mutation (S1036X; 604588.0011) and a missense mutation (D1277A; 604588.0012) in the NEK1 gene. The authors suggested that the phenotypic variability exhibited in this patient might be explained by the location of mutations on the NEK1 protein, since most of the previously reported mutations were located in the N terminus whereas this patient's mutations were in the C terminus.
Genotype/Phenotype Correlations
El Hokayem et al. (2012) reviewed the clinical features of 11 unrelated cases of SRPS type II, 4 of which were due to mutations in the NEK1 gene (SRTD6) and 4 due to mutations in the DYNC2H1 gene (SRTD3); in 3 cases, no mutation was detected in either gene. Lingual and gingival hamartoma were frequently observed in the mutation-positive group, present in 60% of NEK1 cases and in 25% of DYNC2H1 cases, but were absent from the mutation-negative group, whereas lobulated tongue was mostly observed in the mutation-negative group. Kidney cysts, intestinal malrotation, and heart defects were observed in both groups, but holoprosencephaly and polymicrogyria were observed only in the mutation-negative group.
INHERITANCE \- Autosomal recessive \- Digenic recessive GROWTH Height \- Dwarfism, disproportionate HEAD & NECK Head \- Brachycephaly (in some patients) Eyes \- Hyperopia \- Retinal dystrophy, severe generalized (rare) Mouth \- Median cleft lip \- Microform cleft lip \- Cleft-palate \- Lingual hamartoma (in some patients) \- Multiple frenula (in some patients) \- Microglossia (rare) CARDIOVASCULAR Heart \- Ventricular septal defect (rare) \- Atrial septal defect (rare) \- Bicuspid insufficiency, mild (rare) \- Tricuspid insufficiency, mild (rare) RESPIRATORY Nasopharynx \- Hypoplastic epiglottis Larynx \- Malformed larynx Lung \- Pulmonary hypoplasia CHEST External Features \- Narrow thorax \- Pectus carinatum (rare) Ribs Sternum Clavicles & Scapulae \- Short ribs \- Horizontal ribs \- Bifurcated ribs \- Handlebar clavicles \- Squared scapulae ABDOMEN Liver \- Hepatic fibrosis (rare) Pancreas \- Microcystic pancreas (rare) \- Pancreatic fibrosis (rare) Gastrointestinal \- Intestinal malrotation (in some patients) GENITOURINARY External Genitalia (Male) \- Micropenis (in some patients) \- Ambiguous genitalia External Genitalia (Female) \- Ambiguous genitalia Kidneys \- Polycystic kidneys \- Glomerular and renal tubular cysts SKELETAL \- Markedly stunted and disorganized endochondral ossification \- Hypermobile joints Spine \- Platyspondyly, mild (rare) Pelvis \- Underdeveloped lower pelvis (rare) Limbs \- Short long bones \- Mesomelic limb shortening \- Disproportionate shortening of the tibia \- Ovoid tibia shorter than fibula \- Tibial agenesis (in some patients) \- Sclerotic proximal femoral metaphyses (rare) \- Metaphyseal broadening of distal femora, mild (rare) \- Metaphyseal broadening of proximal tibia, mild (rare) Hands \- Postaxial polydactyly \- Preaxial polydactyly \- Brachydactyly (rare) Polysyndactyly Feet \- Hallucal and postaxial polysyndactyly \- Postaxial polydactyly NEUROLOGIC Central Nervous System \- Dilation of lateral ventricles (in some patients) \- Motor delay (rare) \- Speech delay (rare) \- Pachygyria (rare) \- Hypoplastic cerebellar vermis (rare) \- Leukomalacia (rare) PRENATAL MANIFESTATIONS \- Hydrops fetalis MISCELLANEOUS \- Variable features may be present \- Death in perinatal period (in some patients) \- A digenic form caused by heterozygous mutations in both NEK1 ( 604588 ) and DYN2CH1 ( 603297 ) has been reported (last curated June 2018) MOLECULAR BASIS \- Caused by mutation in the never in mitosis gene A-related kinase 1 gene (NEK1, 604588.0001 ) \- Caused by simultaneous heterozygous mutation in both the never in mitosis gene A-related kinase 1 gene (NEK1, 604588.0003 ) and the dynein, cytoplasmic-2, heavy chain-1 gene (DYN2CH1, 603297.0016 ) ▲ 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
|
SHORT-RIB THORACIC DYSPLASIA 6 WITH OR WITHOUT POLYDACTYLY
|
c0024507
| 8,263 |
omim
|
https://www.omim.org/entry/263520
| 2019-09-22T16:23:17 |
{"doid": ["0110092"], "mesh": ["D012779"], "omim": ["263520"], "orphanet": ["93269"], "synonyms": ["Alternative titles", "SHORT RIB-POLYDACTYLY SYNDROME, TYPE II", "SRPS, TYPE II", "MAJEWSKI SYNDROME", "SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA", "POLYDACTYLY WITH NEONATAL CHONDRODYSTROPHY, TYPE II"]}
|
A bronchial leiomyoma is a relatively rare form of lung tumours. These tumours can form in the lower respiratory tract tissue of the bronchi, trachea and other lung tissue. They may also be derived from blood vessels.[1] These tumors typically form from the smooth muscle tissue lining the bronchi. They grow as a solitary tumor attaching themselves to the sides of the bronchi.[2]
## Contents
* 1 Diagnosis
* 2 Treatment
* 3 Epidemiology
* 4 History
* 5 References
## Diagnosis[edit]
This type of tumor can be mistaken for asthma or chronic pulmonary obstructive disease.[1] The determination of a leiomyoma is done by chest x-rays, blood sample and taking a tissue sample of the tumor. An associated test is for tuberculosis, but the results are negative for this infection.[2]
## Treatment[edit]
Surgical removal is the usual treatment to remove the tumor. A less invasive method of removing a small leiomyoma is through a bronchioscopy. Recovery is usually complete.[2]
## Epidemiology[edit]
Bronchial leiomyomas are only 0.1% to 2% of benign lung tumours.[3][1] Bronchial lyeiomyomas comprise 33–45% of respiratory system leiomyomas. People usually develop the tumor in middle age. These growths appear in men and women at the same rate.[2]
## History[edit]
The first bronchial leiomyoma was described by in 1909.[2]
## References[edit]
1. ^ a b c Saoud, Marwan; Patil, Monali; Dhillon, Samjot Singh; Pokharel, Saraswati; Picone, Anthony; Hennon, Mark; Yendamuri, Sai; Harris, Kassem (2016). "Rare airway tumors: an update on current diagnostic and management strategies". Journal of Thoracic Disease. 8 (8): 1922–1934. doi:10.21037/jtd.2016.07.40. ISSN 2072-1439. PMC 4999752. PMID 27621844.-a protocol
2. ^ a b c d e Cárdenas-García, José; Lee-Chang, Alfredo; Chung, Virginia; Shim, Chang; Factor, Stephen; Tibb, Amit (2014). "Bronchial leiomyoma, a case report and review of literature". Respiratory Medicine Case Reports. 12: 59–62. doi:10.1016/j.rmcr.2014.04.004. ISSN 2213-0071. PMC 4061443. PMID 26029544.
3. ^ http://www.humpath.com/spip.php?article21941
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Bronchial leiomyoma
|
c1333386
| 8,264 |
wikipedia
|
https://en.wikipedia.org/wiki/Bronchial_leiomyoma
| 2021-01-18T18:47:58 |
{"umls": ["C1333386"], "wikidata": ["Q18557312"]}
|
Mucous membrane pemphigoid is a rare, chronic, blistering and scarring disease that affects the oral and ocular mucosa. Other mucosal sites that might be affected include the nasopharnyx, larynx, genitalia, rectum, and esophagus. The condition usually begins in late adulthood (e.g. 50's or 60's), affects more women than men, and has a variable prognosis. Scarring of the affected mucosa of the eye may lead to blindness and tends to be the most feared complication. A combination of environmental and genetic factors appear to play a role in the susceptibility of developing cicatricial pemphigoid. Although the specific causes of this condition have not been identified, it is considered an autoimmune disease that is characterized by the production of autoantibodies against basement membrane zone antigens such as BP180, BP230, and laminin 5. Treatment is dependent on the person's specific symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Mucous membrane pemphigoid
|
c0030804
| 8,265 |
gard
|
https://rarediseases.info.nih.gov/diseases/5913/mucous-membrane-pemphigoid
| 2021-01-18T17:58:56 |
{"mesh": ["D010390"], "orphanet": ["46486"], "synonyms": ["Benign mucosal pemphigoid", "Benign mucous membrane pemphigoid", "Cicatricial pemphigoid disease"]}
|
Pallister et al. (1974) described 2 brothers with a mental retardation syndrome characterized by an unusual physiognomy (frontal prominence), anterior cowlick, hypertelorism, antimongoloid orbital slant, and broad, flat nasal bridge like that of the OPD syndrome (311300), midline notch of upper lip and submucous cleft of the hard palate, absent upper central incisors, limited motion at the elbow due to subluxation, camptodactyly, and pes cavus. In addition to the mental retardation, the patients had grand mal seizures. The mother and a sister were considered mildly affected, consistent with heterozygous manifestation of an X-linked trait. Bottani and Schinzel (1993) described a patient thought to have this disorder. Severe mental retardation with seizures was associated with a pattern of facial dysmorphism, including high broad forehead, downslanting palpebral fissures, hypertelorism, peculiar nose, and peculiar upper lip with a median notch (incomplete midline oral cleft). The face was compared to that of a boxer, i.e., pugilistic face.
Goizet et al. (1999) reported 3 patients with the Pallister W syndrome and reviewed the 4 patients in 2 separate families that had previously been described. Constant features seemed to be characteristic facies with prominent mandible and pugilistic appearance, and central nervous system involvement with strabismus, spasticity, and moderate to severe mental retardation.
Hair \- Anterior cowlick Eyes \- Hypertelorism \- Telecanthus \- Down-slanting palpebral fissures \- Alternating esotropia Joints \- Limited elbow motion due to subluxation Neuro \- Mental retardation \- Seizures \- Mild spasticity Facies \- Frontal prominence Teeth \- Absent upper central incisors Mouth \- Midline notch of upper lip \- Submucous cleft hard palate \- Broad uvula Inheritance \- X-linked Limbs \- Cubitus valgus \- Short ulna \- Bowed radius \- Camptodactyly \- Clinodactyly \- Pes cavus \- Metatarsus varus \- Pes planus Nose \- Broad nasal bridge \- Flat nasal bridge Broad nasal tip ▲ Close
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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
|
PALLISTER W SYNDROME
|
c0796110
| 8,266 |
omim
|
https://www.omim.org/entry/311450
| 2019-09-22T16:17:27 |
{"mesh": ["C538106"], "omim": ["311450"], "orphanet": ["2804"], "synonyms": ["Alternative titles", "W SYNDROME"]}
|
A severe, genetic form of pontocerebellar hypoplasia (PCH) characterized by spinal cord anterior horn cell degeneration in addition to pontocerebellar hypoplasia. Clinically, patients manifest with a severe global development deficit that is evident early on from difficulties in feeding and swallowing
## Epidemiology
About 115 patients with pontocerebellar hypoplasia type 1 (PCH1) have been reported.
## Clinical description
The clinical course is severe. Neonates with PCH1 present with hypotonia, impaired swallowing with subsequent feeding difficulties, and progressive, postnatal microcephaly. A severe psychomotor deficit subsequently becomes apparent. If patients survive past infancy, patients have oculomotor manifestations including strabismus, nystagmus, occulomotor apraxia. The most severe cases of PCH1 manifest prenatally with polyhydramnios and arthrogryposis multiplex congenital.
## Etiology
PCH1 is genetically heterogeneous. Recessive mutations in the EXOSC3 gene (9p13.2) are found in 40-50% of patients and are the most prevalent cause of PCH1. Mutations in EXOSC8 (13q13.3) and EXOSC9 (4q27) are recently described as a rare cause of PCH1. Mutations in 3 families have been identified in SLC25A46 (5q22.1) and VRK1 (14q32.2) in 2 families. In single cases, recessive mutations have been found in TSEN54 (17q25.1) RARS2 (6q15). From the small groups reported, severity is suggested to depend on genotype.
## Diagnostic methods
MRI shows pontocerebellar hypoplasia with cerebellar hemispheres variably affected. Variable findings include spinal anterior horn degeneration and absence of pontine hypoplasia. Lack of awareness often results in a delay in diagnosis or a diagnosis is never made.
## Differential diagnosis
PCH type 2 and 4 (TSEN54-related PCH) can be considered. PCH2 is the most common type of PCH, characterized by dyskinesia and seizures. Brain MRI typically shows pontocerebellar hypoplasia with relative sparing of the vermis compared to the hemispheres, similar to PCH1. In PCH1 however, the pons may be unaffected while in PCH2 the ventral pons is flattened. PCH4 is a more severe than PCH2 and often associated with congenital contractures and polyhydramnios. Spinal Muscular Atrophy (SMA) type 1, caused by biallelic pathogenic variants in SMN1, is characterized by anterior horn cell degeneration, similar to that observed in PCH1. Cognitive function is normal in SMA.
## Antenatal diagnosis
Prenatal detection of PCH by ultrasound is unreliable, since cerebellar abnormalities are often not detected at time of the routine screening for structural abnormalities at 20 weeks of gestation. In families in which the causal mutation is detected, prenatal testing or pre-implantation genetic diagnosis (PGD) should be offered.
## Genetic counseling
PCH1 is inherited in an autosomal recessive manner. Genetic counseling is recommended for families of individuals with PCH1. For parents of an affected individual, there is a 25% recurrence risk of having another affected child.
## Management and treatment
Treatment is symptomatic in PCH.
## Prognosis
Prognosis is poor; the majority of patients will only live into infancy. Patients with EXOSC3 mutation have a less severe 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
|
Pontocerebellar hypoplasia type 1
|
c1843504
| 8,267 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2254
| 2021-01-23T17:36:29 |
{"gard": ["10704"], "mesh": ["C548069"], "omim": ["607596", "614678", "616081"], "umls": ["C1843504"], "icd-10": ["Q04.3"], "synonyms": ["Norman disease", "PCH1"]}
|
Benign cystic growth on the pituitary gland
Rathke's cleft cyst
Rathke's cleft cyst in a 53-year-old man with a pituitary adenoma and acromegaly
A Rathke's cleft cyst is a benign growth on the pituitary gland in the brain, specifically a mucin-filled[1] cyst in the posterior portion of the anterior pituitary gland.[2][3] It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40 mm in diameter.[3]
Asymptomatic cysts are commonly detected during autopsies in 2 to 26 percent of individuals who have died of unrelated causes. Females are twice as likely as males to develop a cyst.[3] If a cyst adds pressure to the optic chiasm, it may cause visual disturbances, pituitary dysfunction and headaches.[2] The majority of pituitary patients with chronic headaches have Rathke's cleft cysts. This is believed to be caused by the constant change in volume and the drastic changes in vasopressure from fluctuations in gonadotrophs and ADH.[4]
The treatment of choice for symptomatic cysts is drainage and taking a biopsy.[5][6] Radical excision is more dangerous because of the potential of damaging the patient's pituitary function e.g. ADH storage and lowering growth hormone production.
## References[edit]
1. ^ Abdelzaher, E. Rathke cleft cyst. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumorrathkecyst.html. Accessed May 26th, 2018.
2. ^ a b "Rathke's Cleft Cyst". UCLA. Archived from the original on 2009-09-24. Retrieved 2009-07-27.
3. ^ a b c Omar Islam (2008-05-28). "Rathke Cleft Cyst: Overview". Web MD. Archived from the original on 2009-09-24. Retrieved 2015-05-10.
4. ^ Arman Jahangiri; Jeffrey R. Wagner; Aaron T. Chin; Sung Won Han; Mai T. Tran; Liane M. Miller; Maxwell W. Tom; Rebecca Chen; Sandeep Kunwar; Lewis Blevins; Manish K. Aghi (2015), "Incidence of headache as a presenting complaint in over 1,000 patients with sellar lesions and factors predicting postoperative improvement", Clinical Neurology and Neurosurgery, 132 (May 2015): 16–20, doi:10.1016/j.clineuro.2015.02.006, PMID 25746316
5. ^ Omar Islam (2008-05-28). "Rathke Cleft Cyst: Follow-up". Web MD. Archived from the original on 2009-09-24.
6. ^ Marcella Koch; Benjamin White; Kar-Ming Fung (2004-03-02). "A 45-year-old man with a sellar mass". Department of Pathology, University of Oklahoma Health Sciences Center. Archived from the original on 2009-09-24. Retrieved 2015-05-10.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Rathke's cleft cyst
|
c0752244
| 8,268 |
wikipedia
|
https://en.wikipedia.org/wiki/Rathke%27s_cleft_cyst
| 2021-01-18T19:00:20 |
{"mesh": ["D020863"], "umls": ["C0752244"], "wikidata": ["Q7295649"]}
|
Serpentine fibula-polycystic kidney syndrome
Other namesAcroosteolysis with osteoporosis and changes in skull and mandible
SpecialtyNephrology
Exner syndrome, also known as serpentine fibula polycystic kidney syndrome,[1] is a rare disorder, typified by the afflicted person having oddly formed, s-shaped fibulas as well as the development of numerous cysts in the kidneys.[2]
## Contents
* 1 Symptoms
* 2 Diagnosis
* 3 Treatment
* 4 History
* 5 References
* 6 External links
## Symptoms[edit]
All of the following are usual elements of the syndrome:[3]
* Short stature
* Abnormal calf bone shape (fibula)
* Unusual facial appearance
* Polycystic kidneys
* Abnormally long fibula
* Mild sunken chest
* Large corneas
* Inguinal hernia
* Umbilical hernia
## Diagnosis[edit]
Exner syndrome is sometimes misdiagnosed as interstitial cystitis in its very early stages, but once the fibula begins to malform, Exner is the only real diagnosis.[4]
## Treatment[edit]
This section is empty. You can help by adding to it. (August 2017)
## History[edit]
The syndrome was discovered in June, 1988 by Dr. G. Exner,[5] a researcher at Orthopädische Universitätsklinik Balgrist in Zurich, Switzerland. Exner officially named the disorder serpentine fibula polycystic kidney syndrome, but the term "Exner syndrome" became more prevalent. While some research links it to other, related disorders,[6] most research suggests that Exner syndrome is very distinct.[7]
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): SERPENTINE FIBULA-POLYCYSTIC KIDNEY SYNDROME - 600330
2. ^ Date, C. "SERPENTINE FIBULA-POLYCYSTIC KIDNEY SYNDROME" (PDF). 600330 SERPENTINE FIBULA-POLYCYSTIC KIDNEY SYNDROME. NCBI. Retrieved 2008-11-07.
3. ^ Rosser EM, Mann NP, Hall CM, Winter RM (Apr 1996). "Serpentine fibula syndrome: expansion of the phenotype with three affected siblings". Clin Dysmorphol. 5 (2): 105–13. doi:10.1097/00019605-199604000-00002. PMID 8723560.
4. ^ Oeijord, Nils (2002). Genetic Catastrophe! Sneaking Doomsday?: With a Dictionary of Genetic Damage. iUniverse. ISBN 9780595225651.
5. ^ Exner GU (Jun 1988). "Serpentine fibula—polycystic kidney syndrome. A variant of the Melnick-Needles syndrome or a distinct entity?". Eur. J. Pediatr. 147 (5): 544–6. doi:10.1007/BF00441987. PMID 3409932.
6. ^ Ramos FJ, Kaplan BS, Bellah RD, Zackai EH, Kaplan P (Aug 1998). "Further evidence that the Hajdu-Cheney syndrome and the "serpentine fibula-polycystic kidney syndrome" are a single entity". American Journal of Medical Genetics. 78 (5): 474–81. doi:10.1002/(SICI)1096-8628(19980806)78:5<474::AID-AJMG14>3.0.CO;2-C. PMID 9714016.[dead link]
7. ^ Majewski F, Enders H, Ranke MB, Voit T (Nov 1993). "Serpentine fibula—polycystic kidney syndrome and Melnick-Needles syndrome are different disorders". Eur. J. Pediatr. 152 (11): 916–21. doi:10.1007/BF01957530. PMID 8276023.
## External links[edit]
Classification
D
* ICD-10: M89.5
* OMIM: 600330
* MeSH: C531695
External resources
* Orphanet: 955
* v
* t
* e
Congenital malformations and deformations of urinary system
Abdominal
Kidney
* Renal agenesis/Potter sequence, Papillorenal syndrome
* cystic
* Polycystic kidney disease
* Meckel syndrome
* Multicystic dysplastic kidney
* Medullary sponge kidney
* Horseshoe kidney
* Renal ectopia
* Nephronophthisis
* Supernumerary kidney
* Pelvic kidney
* Dent's disease
* Alport syndrome
Ureter
* Ectopic ureter
* Megaureter
* Duplicated ureter
Pelvic
Bladder
* Bladder exstrophy
Urethra
* Epispadias
* Hypospadias
* Posterior urethral valves
* Penoscrotal transposition
Vestigial
Urachus
* Urachal cyst
* Urachal fistula
* Urachal sinus
* v
* t
* e
Cystic diseases
Respiratory system
* Langerhans cell histiocytosis
* Lymphangioleiomyomatosis
* Cystic bronchiectasis
Skin
* stratified squamous: follicular infundibulum
* Epidermoid cyst and Proliferating epidermoid cyst
* Milia
* Eruptive vellus hair cyst
* outer root sheath
* Trichilemmal cyst and Pilar cyst and Proliferating trichilemmal cyst and Malignant trichilemmal cyst
* sebaceous duct
* Steatocystoma multiplex and Steatocystoma simplex
* Keratocyst
* nonstratified squamous: Cutaneous ciliated cyst
* Hidrocystoma
* no epithelium: Pseudocyst of the auricle
* Mucocele
* other and ungrouped: Cutaneous columnar cyst
* Keratin implantation cyst
* Verrucous cyst
* Adenoid cystic carcinoma
* Breast cyst
Human musculoskeletal system
* Cystic hygroma
Human digestive system
* oral cavity: Cysts of the jaws
* Odontogenic cyst
* Periapical cyst
* Dentigerous cyst
* Odontogenic keratocyst
* Nasopalatine duct cyst
* liver: Polycystic liver disease
* Congenital hepatic fibrosis
* Peliosis hepatis
* bile duct: Biliary hamartomas
* Caroli disease
* Choledochal cysts
* Bile duct hamartoma
Nervous system
* Cystic leukoencephalopathy
Genitourinary system
* Polycystic kidney disease
* Autosomal dominant polycystic kidney
* Autosomal recessive polycystic kidney
* Medullary cystic kidney disease
* Nephronophthisis
* Congenital cystic dysplasia
Other conditions
* Hydatid cyst
* Von Hippel–Lindau disease
* Tuberous sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Serpentine fibula-polycystic kidney syndrome
|
c1838257
| 8,269 |
wikipedia
|
https://en.wikipedia.org/wiki/Serpentine_fibula-polycystic_kidney_syndrome
| 2021-01-18T19:09:52 |
{"mesh": ["C537586"], "orphanet": ["2853"], "wikidata": ["Q7455128"]}
|
## Description
Bulimia nervosa (BN) is a psychiatric disorder characterized by episodes of binge-eating (eating an unusually large amount of food in a discrete period of time and feeling out of control), compensatory behavior (e.g., self-induced vomiting or laxative abuse), and over-concern with weight and shape.
Eating disorders such as bulimia nervosa are complex disorders that can be influenced by many genes.
Inheritance
There is evidence that bulimia (as well as the related eating disorder anorexia nervosa (AN; see 606788) and eating disorders not otherwise specified) is strongly familial (Lilenfeld et al., 1998; Strober et al., 2000; Bulik et al., 2000). Twin studies estimate the heritability of syndromic bulimia to be 54 to 83% (Kendler et al., 1991; Bulik et al., 1998; Wade et al., 1999; Kortegaard et al., 2001).
Mapping
Bulik et al. (2003) conducted a linkage analysis in multiplex families with eating disorders that were identified through a proband with bulimia nervosa. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multiplex maximum lod score (MLS) of 2.92 on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it could be measured, Bulik et al. (2003) performed linkage analysis in a subset of 133 families in which at least 2 affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provided evidence for the presence of a susceptibility locus (BULN1) for bulimia nervosa on 10p. Another region on 14q met the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 cM from the end of 14p.
Bacanu et al. (2005) measured over 100 attributes thought to be related to liability to eating disorders in affected individuals of multiplex families from the AN cohort that had previously been studied by Grice et al. (2002) and Devlin et al. (2002) and the BN cohort that had previously been studied by Bulik et al. (2003). Six traits were selected for linkage analysis on the basis of expert evaluation and statistical analysis, including obsessionality, age at menarche, anxiety for quantitative trait locus (QTL) linkage analysis, lifetime minimum body mass index (BMI), concern over mistakes, and food-related obsessions. Using QTL linkage analysis, the BN cohort produced 4 suggestive signals: for age at menarche at 10p13 and for anxiety for QTL linkage analysis at 1q31.1, 4q35.2, and 8q13.1. Using covariate-based linkage analysis, the BN cohort showed the most significant and suggestive linkages: for minimum BMI, 1 significant linkage at 4q21.1 and 3 suggestive linkages at 3p23, 10p13, and 5p15.3; for concern over mistakes, 2 significant linkages at 16p13.3 and 14q21.1 and 3 suggestive linkages at 4p15.33, 8q11.23, and 10p11.21; and for food-related obsessions, 1 significant linkage at 14q21.1 and 5 suggestive linkages at 4p16.1, 10p13.1, 8q11.23, 16p13.3, and 18p11.31. For the AN cohort, results were less compelling. Using QTL linkage analysis, they found 2 suggestive linkages, for obsessionality at 6q21 and for anxiety for QTL linkage analysis at 9p21.3. Covariate-based linkage analysis of the AN cohort revealed 5 suggestive signals: for minimum BMI at 4q13.1, for concern over mistakes, at 11p11.2 and 17q25.1, and for food-related obsessions at 17q25.1 and 15q26.2. There was minimum overlap between the 2 cohorts for substantial linkage signals.
Molecular Genetics
Monteleone and Maj (2008) reviewed the genetics of eating disorders, including bulimia nervosa, and stated that there was no convincing evidence for association of candidate genes with eating disorders; they noted that the heterogeneity of eating disorder phenotypes was most likely responsible for the contradictory and inconclusive results.
### Associations Pending Confirmation
For discussion of an association between susceptibility to bulimia (formerly symbolized BULN2) and polymorphism in the BDNF gene, see 113505.0002 and 113505.0003.
INHERITANCE \- Multifactorial NEUROLOGIC Behavioral Psychiatric Manifestations \- Recurrent episodes of binge eating \- Recurrent inappropriate conpensatory behavior to prevent weight gain, including self-induced vomiting, laxative or diuretic abuse, fasting, excessive exercise \- Overconcern with weight and body shape \- Feelings of guilt associated with episodes MOLECULAR BASIS \- Susceptibility conferred by polymorphisms in the brain-derived neurotrophic factor gene (BDNF, 113505.0002 and 113505.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
BULIMIA NERVOSA, SUSCEPTIBILITY TO
|
c1843776
| 8,270 |
omim
|
https://www.omim.org/entry/607499
| 2019-09-22T16:09:08 |
{"omim": ["607499"], "synonyms": ["Alternative titles", "BN"]}
|
Hereditary spastic paraplegia (HSP) is a group of hereditary, degenerative, neurological disorders that primarily affect the upper motor neurons. Upper motor neurons in the brain and spinal cord deliver signals to the lower motor neurons, which in turn, carry messages to the muscles. In hereditary spastic paraplegia, upper motor neurons slowly degenerate so the muscles do not receive the correct messages, causing progressive spasticity (increased muscle tone/stiffness) and weakness of the legs. This leads to difficulty walking. As degeneration continues, symptoms worsen. If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved. In these cases, additional symptoms, including impaired vision, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and/or deafness, occur. The different forms of HSP are caused by mutations in different genes. Inheritance varies. There are no specific treatments to prevent, slow, or reverse HSP. Individual symptoms may be treated with medications and/or physical therapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hereditary spastic paraplegia
|
c2931355
| 8,271 |
gard
|
https://rarediseases.info.nih.gov/diseases/6637/hereditary-spastic-paraplegia
| 2021-01-18T18:00:01 |
{"mesh": ["C536864"], "orphanet": ["685"], "synonyms": ["HSP", "Familial spastic paraparesis", "FSP", "Familial spastic paraplegia", "Hereditary spastic paraparesis", "SPG", "Strümpell-Lorrain disease"]}
|
A number sign (#) is used with this entry because of evidence that frontonasal dysplasia-2 (FND2) is caused by homozygous mutation in the ALX4 gene (605420) on chromosome 11p11.
For a general description and a discussion of genetic heterogeneity of frontonasal dysplasia, see FND1 (136760).
Clinical Features
Kayserili et al. (2009) described 2 consanguineous Turkish families with an autosomal recessive form of frontonasal dysplasia characterized by a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, cryptorchidism, agenesis of the corpus callosum, total alopecia, and mental retardation. No limb anomalies were reported. Skin from a biopsy of an affected individual demonstrated a hypomorphic interfollicular epidermis with reduced suprabasal layers associated with impaired interfollicular epidermal differentiation. Hair follicle-like structures were present but showed altered differentiation.
Kariminejad et al. (2008, 2014) reported a girl, born to consanguineous Iranian parents, with FND2. At age 2 years, she had very sparse hair, eyebrows, and eyelashes, and absence of body hair. Craniofacial abnormalities included hypertelorism, short and upslanting palpebral fissures, telecanthus, wide and flat nasal bridge, thick and broad columella, hypoplasia of the alae nasi, and notched nostrils. Imaging of the skull showed cranium bifidum with parietal foramina and normal facial skeletal bones; brain imaging showed small abnormally shaped occipital lobes and mild abnormalities of the corpus callosum. Skin biopsy showed mild hyperkeratosis and underdeveloped hair follicles. The patient also had reduced lacrimation and reduced sweating. Cognition was normal. The patient's father had bilateral small parasagittal parietal foramina and mild dysplastic changes in the cerebellum. The mother, who had milder cerebellar findings than the father, had impressions on the inner surface of the parasagittal parietal bones.
### Clinical Variability
Kayserili et al. (2012) reported a boy, born of consanguineous Turkish parents, with a mild form of FND2. He had hypertelorism, upslanting palpebral fissures, wide nasal bridge and ridge, bifid nasal tip, broad columella, cleft alae nasi, and an upper labiogingival sulcus. Skull and brain imaging showed bilateral parietal foramina and a mildly hypoplastic, kinked body of the corpus callosum and underdevelopment of the vermis. Psychomotor development was normal.
Inheritance
The transmission pattern of FND2 in the family reported by Kariminejad et al. (2014) was consistent with autosomal recessive inheritance.
Mapping
In a Turkish family segregating frontonasal dysplasia, Kayserili et al. (2009) used homozygosity mapping to localize the disease locus to a 19.8-Mb segment on chromosome 11p11.2-q12.3.
Molecular Genetics
In affected members of 2 consanguineous Turkish families segregating frontonasal dysplasia, Kayserili et al. (2009) identified homozygosity for a 793C-T nonsense mutation in the Aristaless-like-4 gene (605420.0008). The mutation was predicted to result in a premature stop codon (R265X), truncating 146 amino acids of the protein including a part of the highly conserved homeodomain and the C-terminal paired tail domain. Kayserili et al. (2009) concluded that ALX4 plays a critical role in craniofacial development as well as in skin and hair follicle development.
In a boy, born of consanguineous Turkish parents, with a mild form of FND2, Kayserili et al. (2012) identified a homozygous missense mutation in the ALX4 gene (Q225E; 605420.0011). Functional studies were not performed. The parents, who were heterozygous for the mutation, had uncovered bilateral parietal foramina of small size. Kayserili et al. (2012) postulated that the less severe phenotype observed in this patient compared to the patients reported by Kayserili et al. (2009) was due to the missense mutation retaining some functionality.
In a girl, born of consanguineous Iranian parents, with FND2, Kariminejad et al. (2014) identified a homozygous frameshift mutation in the ALX4 gene (605420.0014).
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Small head Eyes \- Hypertelorism \- Upslanting palpebral fissures \- Short palpebral fissures \- Decreased lacrimation (1 patient) Nose \- Wide nasal tip \- Bifid nasal tip \- Wide nasal bridge \- Depressed nasal bridge \- Depressed nasal ridge \- Cleft alae nasi \- Short, broad columella SKELETAL Skull \- Parietal foramina \- Cranium bifidum \- Craniosynostosis SKIN, NAILS, & HAIR Skin \- Decreased sweating (1 patient) Hair \- Alopecia (in some patients) \- Sparse hair \- Sparse eyelashes \- Sparse eyebrows NEUROLOGIC Central Nervous System \- Intellectual disability (in some patients) \- Hypoplasia of the corpus callosum \- Aplasia of the corpus callosum \- Cerebellar vermis hypoplasia MISCELLANEOUS \- Variable severity MOLECULAR BASIS \- Caused by mutation in the aristaless-like 4, mouse, homolog of, gene (ALX4, 605420.0008 ) ▲ 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
|
FRONTONASAL DYSPLASIA 2
|
c3150703
| 8,272 |
omim
|
https://www.omim.org/entry/613451
| 2019-09-22T15:58:37 |
{"omim": ["613451"], "orphanet": ["228390"], "synonyms": ["ALX4-related FNDAG", "Craniofrontonasal dysplasia with alopecia and hypogonadism", "Frontonasal dysplasia type 2", "Frontonasal dysplasia with alopecia and genital abnomality"]}
|
A number sign (#) is used with this entry because childhood hypophosphatasia can be caused by homozygous, compound heterozygous, or heterozygous mutation in the ALPL gene (171760) on chromosome 1p36.
Description
Hypophosphatasia is an inborn error of metabolism characterized clinically by defective bone mineralization and biochemically by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Fraser (1957) classified forms of hypophosphatasia according to age of onset: perinatal (see 241500), infantile (241500), childhood, and adult (146300). Whyte (1988) indicated a fifth form of hypophosphatasia with primarily only dental manifestations, referred to as odontohypophosphatasia (see 241500). All of these forms are allelic.
Clinical Features
Hu et al. (2000) described a 4-generation Texas family segregating autosomal dominant hypophosphatasia in both children and adults. The probands were a 6-year-old girl and her twin brother, who exhibited enamel hypoplasia and the premature loss of fully rooted anterior teeth at age 3.5 years; histologic examination of a tooth demonstrated a complete absence of cementum on the root surface. Lateral cephalometric radiograph showed multiple radiolucent spots with wormian bone in the occipital region, and enlarged pulp chambers in the mandibular canines and first primary molars were evident in the panorex. Radiographs of the long bones and chest revealed no additional skeletal abnormalities. Serum PLP and urine phosphoethanolamine (PEA) were abnormally high in both of the twins and a definitive diagnosis of hypophosphatasia was made, which was supported by findings in other members of the kindred.
Lia-Baldini et al. (2001) reported a 15-month-old girl with a phenotype suggestive of childhood hypophosphatasia, whose father had recurrent dental caries in his third decade despite being raised with fluoridated water, which the authors suggested represented odontohypophosphatasia. A paternal aunt had died at 7 days of apparent neonatal hypophosphatasia, with x-rays showing poorly mineralized ribs and skull, and the paternal grandmother lost all her permanent teeth in her third decade and subsequently developed osteoporosis.
Molecular Genetics
In 2 sibs with the mild childhood form of hypophosphatasia, Henthorn et al. (1992) identified compound heterozygosity for 2 missense mutations in the ALPL gene (171760.0003 and 171760.0008).
In an 11-year-old child with hypophosphatasia, Zurutuza et al. (1999) identified compound heterozygosity for 2 missense mutations in the ALPL gene (171760.0013 and 171760.0014).
In a 4-generation Texas family segregating autosomal dominant hypophosphatasia in both children and adults, Hu et al. (2000) identified a heterozygous missense mutation in the ALPL gene (171760.0015).
In a 15-month-old girl and her father, who had phenotypes suggestive of childhood hypophosphatasia and odontohypophosphatasia, respectively, Lia-Baldini et al. (2001) identified heterozygosity for a missense mutation in the ALPL gene (171760.0021).
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Craniostenosis \- Dolichocephaly Face \- Frontal bossing Eyes \- Proptosis Teeth \- Dental caries \- Premature deciduous tooth loss (less than five years of age) CHEST Ribs Sternum Clavicles & Scapulae \- Rachitic rosary SKELETAL \- Rachitic skeletal changes Limbs \- Bowed legs \- Characteristic metaphyseal radiolucency SKIN, NAILS, & HAIR Skin \- Skin dimple over apex of long bone angulation NEUROLOGIC Central Nervous System \- Seizures \- Myopathy LABORATORY ABNORMALITIES \- Low alkaline phosphatase \- Phosphoethanolaminuria \- Elevated plasma and urine inorganic pyrophosphate (PPi) MISCELLANEOUS \- Delayed onset of walking \- Presentation after 6 months \- Waddling gait MOLECULAR BASIS \- Caused by mutation in the alkaline phosphatase gene (ALPL, 171760.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HYPOPHOSPHATASIA, CHILDHOOD
|
c0020630
| 8,273 |
omim
|
https://www.omim.org/entry/241510
| 2019-09-22T16:26:35 |
{"doid": ["0110915"], "mesh": ["D007014"], "omim": ["241510"], "orphanet": ["436", "247667"], "genereviews": ["NBK1150"]}
|
A rare neurometabolic disease characterized by infantile onset of rapidly progressive neurological deterioration, typically precipitated by a febrile illness. Patients present with hypotonia, loss of previously acquired motor milestones and cognitive skills, ataxia, nystagmus, tremor, seizures, tetraparesis, and respiratory failure, eventually resulting in a vegetative state. Imaging of the brain and spinal cord may show white matter abnormalities, cerebral atrophy, cerebellar edema, and spinal myelopathy. Subacute development of extensive bullous skin lesions within weeks of onset of neurological symptoms has also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
NAD(P)HX epimerase deficiency
|
c4310675
| 8,274 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=555407
| 2021-01-23T18:30:09 |
{"omim": ["617186"], "synonyms": ["Apolipoprotein A-I binding protein deficiency"]}
|
A number sign (#) is used with this entry because of evidence that susceptibility to nonmedullary thyroid cancer-2 (NMTC2) is conferred by heterozygous mutation in the SRGAP1 gene (606523) on chromosome 12q14.
Description
Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; 155240). NMTC is classified into 4 groups: papillary, follicular, Hurthle cell (607464), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a minor component of a familial cancer syndrome (e.g., familial adenomatous polyposis, 175100, Carney complex, 160980) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009).
Follicular thyroid cancer (FTC) accounts for approximately 15% of NMTC and is defined by invasive features that result in infiltration of blood vessels and/or full penetration of the tumor capsule, in the absence of the nuclear alterations that characterize papillary carcinoma. FTC is rarely multifocal and usually does not metastasize to the regional lymph nodes but tends to spread via the bloodstream to the lung and bones. An important histologic variant of FTC is the oncocytic (Hurthle cell, oxyphilic) follicular carcinoma composed of eosinophilic cells replete with mitochondria (summary by Bonora et al., 2010).
For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).
Molecular Genetics
He et al. (2013) performed genomewide linkage analysis in 38 families with PTC and identified SRGAP1 in the linkage peak as a candidate gene. Two missense mutations in the Fes/CIP4 homology domain (Q149H, 606523.0001 and A275T, 606523.0002) segregated with disease in 1 family each; 1 missense variant in the RhoGAP domain (R617C; 606523.0003) occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42 (116950), a key function of SRGAP1, was severely impaired by the Q149H and R617C variants.
INHERITANCE \- Autosomal dominant \- Somatic mutation NEOPLASIA \- Nonmedullary thyroid carcinoma (papillary and follicular) MISCELLANEOUS \- Somatic mutations found in NRAS ( 164790.0002 ) MOLECULAR BASIS \- Susceptibility conferred by mutation in the slit-robo GTPase-activating protein, rho, 1 gene (SRGAP1, 606523.0001 ) ▲ 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
|
THYROID CANCER, NONMEDULLARY, 2
|
c4225426
| 8,275 |
omim
|
https://www.omim.org/entry/188470
| 2019-09-22T16:32:33 |
{"doid": ["3962"], "omim": ["188470"], "orphanet": ["319487"], "synonyms": ["FNMTC", "Familial pure nonmedullary thyroid carcinoma"]}
|
## Description
Autosomal recessive deafness-96 (DFNB96) is a form of nonsyndromic sensorineural severe to profound hearing impairment with prelingual onset (summary by Ansar et al., 2011).
Clinical Features
Ansar et al. (2011) reported a consanguineous Pakistani family in which 4 individuals had prelingual onset of severe to profound nonsyndromic deafness affecting all frequencies.
Inheritance
The transmission pattern of nonsyndromic deafness in the family reported by Ansar et al. (2011) was consistent with autosomal recessive inheritance.
Mapping
By genomewide linkage analysis of a consanguineous Pakistani family with nonsyndromic deafness, Ansar et al. (2011) found linkage to an 11.67-Mb region on chromosome 1p36.31-p36.13 between SNPs rs3817914 and rs477558, designated DFNB96. A maximum 2-point lod score of 3.2 was found at rs8627, and a maximum multipoint lod score of 3.8 was obtained at 15 contiguous markers from rs630075 to rs10927583. Sequencing of the ESPN gene (606351) and 2 genes that cause Bartter syndrome, CLCNKA (602024) and CLCNKB (602023), did not identify pathogenic variants.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, severe to profound, affecting all frequencies MISCELLANEOUS \- Prelingual onset \- One consanguineous Pakistani family has been reported (as of January 2012) ▲ 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
|
DEAFNESS, AUTOSOMAL RECESSIVE 96
|
c3888337
| 8,276 |
omim
|
https://www.omim.org/entry/614414
| 2019-09-22T15:55:23 |
{"doid": ["0110538"], "omim": ["614414"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
|
A rare non-syndromic limb reduction defect characterized by the congenital total absence of the hand and wrist with no bony elements distal to the radius or ulna. The malformation can be unilateral or bilateral.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Acheiria
|
c0265594
| 8,277 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=294983
| 2021-01-23T18:55:45 |
{"icd-10": ["Q71.3"], "synonyms": ["Congenital absence of hand"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic ataxia-4 (SPAX4) is caused by homozygous mutation in the MTPAP gene (613669) on chromosome 10p11. One such family has been reported.
For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).
Clinical Features
Crosby et al. (2010) reported a large consanguineous family of Old Order Amish origin in which 7 individuals had early childhood onset of a slowly progressive neurodegenerative disorder characterized primarily by cerebellar ataxia, spastic paraparesis, dysarthria, and optic atrophy. At the time of the report, the patients ranged in age from 2 to 27 years. Most patients had delayed walking with frequent falls and delayed speech development. The 4 older patients all had optic atrophy, and 2 had nystagmus. There was gait and limb ataxia, increased tone in the upper and lower limbs, hyperreflexia at the knee joint, and extensor plantar responses. The older individuals tended to have slow and spastic tongue movements, brisk jaw jerk, and loss of reflexes in the upper limb and ankles later in the disease, indicating the progressive nature of the disorder. All were still mobile without obvious intellectual deterioration, although some had learning disabilities and emotional lability.
Mapping
By genomewide linkage and homozygosity analysis of an Amish family with autosomal recessive spastic ataxia, Crosby et al. (2010) identified a 6.5-Mb region on chromosome 10p11.23 between markers rs1144522 and rs910967 (maximum lod score of 7.64).
Molecular Genetics
By candidate gene sequencing of a region on chromosome 10p11.23, Crosby et al. (2010) identified a homozygous mutation in the MTPAP gene (N478D; 613669.0001) in 6 affected members of a large consanguineous family of Old Order Amish origin with spastic ataxia-4.
Pathogenesis
Wilson et al. (2014) performed studies on fibroblasts from 2 patients and 1 unaffected obligate mutation carrier from the Amish family with SPAX4 reported by Crosby et al. (2010). Mitochondrial mRNA from patient cells showed a lack of polyadenylation and a concomitant increase in oligoadenylated species. Heterozygous cells were similar to controls, with a mild increase in oligoadenylated mRNA. Homozygous mutant cell lines showed a decrease in oxidative phosphorylation activity, as well as a severe decrease in the amounts and activities of mitochondrial complexes I and IV. The findings were consistent with a selective defect in mitochondrial gene expression, and the defects were rescued by expression of wildtype MTPAP.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Brisk jaw jerk Eyes \- Optic atrophy \- Nystagmus Mouth \- Poor oromandibular coordination \- Slow, spastic tongue movements NEUROLOGIC Central Nervous System \- Delayed walking \- Cerebellar ataxia, limb and trunk \- Spastic paraparesis \- Hyperreflexia of the lower limbs \- Increased tone in the upper limbs (occur later) \- Extensor plantar responses \- Delayed speech \- Dysarthria \- Learning difficulties \- Hyporeflexia (occurs later) Behavioral Psychiatric Manifestations \- Emotional lability (in some) LABORATORY ABNORMALITIES \- Fibroblasts shows defects in oxidative phosphorylation \- Decreased amount and activity of mitochondrial complexes I and IV MISCELLANEOUS \- Onset in early childhood \- Slowly progressive disorder \- Most retain independent ambulation \- One family from the Old Order Amish has been reported (last curated January 2015) MOLECULAR BASIS \- Caused by mutation in the mitochondrial poly(A) polymerase gene (MTPAP, 613669.0001 ) ▲ 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
|
SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE
|
c3150925
| 8,278 |
omim
|
https://www.omim.org/entry/613672
| 2019-09-22T15:57:54 |
{"doid": ["0050943"], "omim": ["613672"], "orphanet": ["254343"], "synonyms": ["Autosomal recessive spastic ataxia type 4", "SPAX4"]}
|
## Clinical Features
Mangino et al. (2001) reported a 4-generation Italian family segregating autosomal dominant progressive nonsyndromic hearing loss. Onset occurred between 10 and 40 years of age. Deafness first involved the higher frequencies and progressed to middle frequencies, resulting in a characteristic sloping audiogram.
Mapping
Mangino et al. (2001) performed a genome scan with polymorphic microsatellite markers in an Italian family segregating autosomal dominant nonsyndromic hearing loss and mapped the disorder, designated DFNA30, to an 18-cM region on 15q25-q26 with a maximum 2-point lod score of 4.12 at theta = 0.00 for marker D15S1004. Haplotype and multipoint analysis identified a critical interval between markers D15S151 and D15S130. The critical region did not overlap with the DFNB16 locus (603720) but partially coincided with the otosclerosis-1 locus (OTSC1; 166800), leading the authors to suggest that the DFNA30 hearing impairment might be an allelic disease of OTSC1.
Molecular Genetics
By sequence analysis of candidate genes mapping to the DFNA30 interval in members of an Italian family segregating nonsyndromic hearing loss, Mangino et al. (2001) found no mutations in the aggrecan-1 (155760) and PTD014 genes.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural bilateral symmetric, progressive (high frequency loss followed by middle frequency loss) MISCELLANEOUS \- Based on one 4-generation Italian family (last curated August 2015) \- Age of onset from 10 to 40 years ▲ 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
|
DEAFNESS, AUTOSOMAL DOMINANT 30
|
c1847972
| 8,279 |
omim
|
https://www.omim.org/entry/606451
| 2019-09-22T16:10:22 |
{"doid": ["0110560"], "mesh": ["C564706"], "omim": ["606451"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"]}
|
A number sign (#) is used with this entry because of evidence that variation in the IRF4 gene (601900) on chromosome 6p25 influences skin, hair, and eye pigmentation (SHEP8).
For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see 227220.
Mapping
Among 2,986 Icelanders, Sulem et al. (2007) carried out a genomewide association study (GWAS) for variants associated with hair and eye pigmentation, skin sensitivity to sun, and freckling. The most closely associated SNPs were then tested for replication in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. Sulem et al. (2007) found association of the A allele of a single-nucleotide polymorphism (SNP), rs1540771, on chromosome 6p25.3 between the IRF4 and SEC5L1 (615329) genes, with the presence of freckles in Icelandic and Dutch population samples (discovery odds ratio (OR) = 1.40, p = 3.7 x 10(-18)). Secondary associations of this allele were found with brown rather than blond hair and with skin sensitivity to sun. The frequency of rs1540771 is approximately 50% in European populations, but 30% and 5% in East Asian and Nigerian Yoruba HapMap samples, respectively.
Molecular Genetics
In a multistage GWAS of 4 studies comprising 7,028 individuals of European ancestry, Han et al. (2008) found a significant association between hair color (black to blond; black to red) and a C-to-T SNP (rs12203592) (601900.0001) in the IRF4 gene (p = 7.46 x 10(-127)). The SNP was also associated with skin color (p = 6.2 x 10(-14)), eye color (p = 6.1 x 10(-13)), and skin tanning response to sunlight (p = 3.9 x 10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771.
In a genomewide association study of 1,810 Australian adolescent twins, Duffy et al. (2010) found a significant association between rs12203592 and flat nevus lesions. Each T allele of this SNP increased the nevus count for flat lesions by an average of 30 (5 x 10(-23)). The effects of genotype were similar on sun-exposed and intermittently exposed sites. An opposite effect of this SNP on nevus association was found among 1,470 parents of the adolescents, indicating a strong gene-by-age interaction. The same gene-by-age interaction was replicated in cohorts from the UK and Sweden. The data suggest that rs12203592 T carriers are prone to developing many nevi at a young age, but these nevi involute faster than those that develop later, with few remaining by late adulthood.
In combined analysis of adult melanoma case-control data from Australia, the UK, and Sweden, the C allele of rs12203592 was mildly associated with melanoma (odds ratio (OR) of 1.15, p = 4 x 10(-3)), most often on the trunk, which is consistent with a nevus-count pathway of melanoma development.
In a case-control study of 1,738 Australian patients with cutaneous malignant melanoma and 4,517 controls, Duffy et al. (2010) did not find a significant association between rs12203592 and melanoma risk, although this SNP was strongly associated with pigmentation.
Praetorius et al. (2013) stated that the T minor allele of rs12203592 is not seen in sub-Saharan Africans or East Asians, and is most common in individuals of European descent. Among 2,230 Icelanders, there was a strong association between the T allele and the presence of freckles, brown hair, and high sensitivity of skin to sun exposure; a lesser association was found with eye color. In vitro functional expression studies in mouse and human melanin-containing cells showed that the SNP altered the function of the melanocyte enhancer in IRF4 by disrupting a TFAP2A (107580)-binding site, thereby suppressing the induction of IRF4 expression and impairing the induction of TYR (606933).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 8
|
c2673265
| 8,280 |
omim
|
https://www.omim.org/entry/611724
| 2019-09-22T16:02:53 |
{"mesh": ["C567096"], "omim": ["611724"], "synonyms": ["Alternative titles", "SKIN/HAIR/EYE PIGMENTATION 8, BROWN HAIR", "SKIN/HAIR/EYE PIGMENTATION 8, FAIR SKIN", "SKIN/HAIR/EYE PIGMENTATION 8, BLUE/LIGHT EYE COLOR", "SKIN/HAIR/EYE PIGMENTATION 8, FRECKLING/SUNBURN"]}
|
A rare, usually benign, chronic, form of systemic mastocytosis (SM) characterized by an abnormal accumulation of neoplastic mast cells (MCs) mainly in the bone marrow (BM) but also in other organs or tissues such as preferably the skin.
## Epidemiology
Indolent SM (ISM) represents 90% of all cases of SM for which the prevalence in Europe is estimated between 1/7,700 and 1/10,400.
## Clinical description
ISM mainly affects adults and typically presents with skin lesions (ISM+), usually in the form of urticaria pigmentosa (UP), while only a few patients have no skin lesions (ISM-). In addition, ISM patients frequently suffer from MC mediator-related symptoms, including pruritus, flushing, syncope, headache and gastro-intestinal (GI) events (vomiting, diarrhea, abdominal pain). Isolated BM mastocytosis (BMM) is a provisional subcategory of ISM typically characterized by absence of cutaneous lesions of ISM and normal to slightly elevated basal tryptase levels. In most patients with BMM, the KIT D816V allele burden in the peripheral blood is low. A BM smear typically reveals small-sized clusters and aggregates of MCs. In both ISM and BMM, patients have a high risk to develop severe anaphylactic reactions to various exogenous substances (triggers/allergens) such as insect bites. Presentation of severe osteoporosis or even spontaneous fractures is also possible.
## Etiology
Although the etiology of ISM is not fully understood, an activating mutation of KIT, usually KIT D816V, is found in the MCs of virtually all ISM cases. This mutation probably accounts for the abnormal accumulation of MCs in organ(s)/tissue(s). In some cases, the mutation is found primarily in the neoplastic MC compartment; in other cases, the mutation may be detected in other mature BM and PB cells such as basophils, eosinophils, neutrophils, as well as B- and T-lymphocytes. Furthermore, precursors of erythroid and myeloid cells as well as CD34+ progenitors may carry the KIT D816V mutation, suggesting the involvement of a pluripotent stem cell.
## Diagnostic methods
SM diagnosis is established using the WHO consensus criteria and is subsequently categorized according to the presence of B-findings and C-findings. In ISM and BMM there are neither B-findings, nor C-findings.
## Differential diagnosis
Differential diagnoses include all the other forms of SM as well as other causes of MC activation syndromes (MCAS): primary (clonal, but not fulfilling SM diagnostic criteria) MCAS; secondary MCAS where an IgE-dependent allergy or another reactive inflammatory disease process is present; and idiopathic MCAS where neither clonal MC nor an IgE-dependent allergy or another underlying condition/disease can be documented. Additional differential diagnoses include other forms of mastocytosis (pure cutaneous mastocytosis, mast cell sarcoma), endocrine disorders (adrenal tumors, VIPoma, gastrinoma), some gastrointestinal pathologies. In ISM-, the differential diagnosis is BMM. It should also be possible to distinguish Waldenström disease.
## Management and treatment
Indolent SM patients, as well as those with BMM, usually only require symptomatic treatments. The main objective is to reduce the symptoms of MC activation, such as pruritus, flushes and gastrointestinal cramps. In case of pruritus or skin manifestations, antihistamines H1 (anti-H1) are used. For GI tract manifestations, anti-H2 are effective and can be combined with anti-H1, with di-sodium cromoglycate or with leukotriene inhibitors. Corticoids can suppress antihistamines recalcitrant symptoms. Epinephrine is indicated for hypotension, which may be spontaneous or observed after an insect bite. Patients should be trained to self-administer injectable epinephrine. Of note, some SM patients may suffer from bee or wasp venom allergy. In these patients, specific immunotherapy should be administered lifelong to ensure protection. For patients with SM and osteoporosis, biphosphonates are recommended with adequate supplementation of calcium and vitamin D.
## Prognosis
The evolution of ISM and of BMM is slow and benign. The prognosis is generally good and life expectancy is similar to that of the general population. However, some of these patients may finally progress to SSM, SM-AHN, ASM or even MCL; multilineage KIT D816V involvement is probably the most important prognostic criterion for progression of ISM to more advanced SM subtypes.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Indolent systemic mastocytosis
|
c0272203
| 8,281 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98848
| 2021-01-23T17:54:31 |
{"mesh": ["D034721"], "umls": ["C0272203"], "icd-10": ["D47.0"]}
|
A number sign (#) is used with this entry because of evidence that menstrual cycle-dependent periodic fever can be caused by heterozygous mutation in the HTR1A gene (109760) on chromosome 5q11.
Description
Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines. Rare menstrual cycle-dependent febrile episodes have been reported, some of which have shown a luteal-phase-dependent pattern (summary by Jiang et al., 2012).
Clinical Features
Rutanen et al. (1993) reported 2 Finnish women who had recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle, who also had continuously elevated serum levels of TNF (191160) and IL6 (147620). The first woman developed monthly recurrent fevers, up to 39.5 degrees Celsius and lasting 1 week, at age 17 years; evaluation revealed only mild hypercortisolism. At age 18, she developed severe tremor and ataxia in association with the fever, which continued for a 2-month period. She was found to be pregnant, which was terminated due to her continued fever and neurologic symptoms; after termination, the fever and associated symptoms disappeared, but subsequently the fever and hypercortisolism recurred. Two more pregnancies were associated with fever, tremor, and ataxia, with resolution of symptoms after termination of the pregnancies. Upon recognition of an association between fever and the midluteal phase of the menstrual cycle, progesterone levels were measured and found to be normal. Three more pregnancies were associated with fever and ended in spontaneous abortions at 6 to 7 weeks' gestation. At age 28, the patient still had midluteal phase increases in temperature, but the associated symptoms were markedly milder than in the early years of the disorder. The second patient developed fever, myalgia, and lower extremity weakness after beginning use of a triphasic oral contraceptive at age 18. Evaluation after 6 weeks of continuous fever revealed no infectious focus. The oral contraceptive pill was discontinued, and the patient's symptoms improved dramatically; however, the patient was subsequently readmitted for evaluation several times due to recurrent fevers occurring at days 19 through 25 of the menstrual cycle, concomitant with the highest levels of serum progesterone. No signs of infection were detected and the only abnormal findings were mildly elevated serum cortisol and 11-deoxycorticosterol as well as 24-hour urinary excretion of cortisol. Administration of progesterone and progestins triggered fever in both patients, and treatment with antiprogesterone (RU486) prevented the fever and associated symptoms, which recurred with cessation of RU486. To prevent the endogenous progesterone surge, the first patient also underwent ovarian suppression by treatment with the GnRH (152760) antagonist nafarelin and remained afebrile. Serum levels of TNF and IL6 were consistently elevated in both patients, 4- to 6-fold and 4- to 4.5-fold, respectively, greater than the levels observed in healthy female controls. Rutanen et al. (1993) noted that fever did not appear immediately after ovulation, suggesting that a certain threshold of serum progesterone was required to trigger it.
Nakamura and Hino (2005) reported a 30-year-old Japanese woman who developed recurrent high fevers (greater than 38 degrees Celsius) associated with her menstrual cycle 3 years after being treated with interferon-beta for a hepatitis C infection. The fevers occurred a few days after ovulation, and when ovarian function was suppressed by GnRH agonist (GnRHa), the symptoms disappeared. While in anovulation, the patient received estrogen followed by estrogen with progestogen, which resembles the sex hormone milieu of a normal menstrual cycle without the luteinizing hormone (LH; 152780) surge; this treatment did not induce the symptoms. When human chorionic gonadotropin (hCG; 118860) was injected on the beginning day of estrogen with progestogen following treatment with estrogen alone, the previous symptoms reappeared. However, hCG injection without estrogen priming did not induce symptoms, indicating that the LH surge after estrogen priming caused the symptoms. Measurements of inflammatory cytokines, including TNF, IL6, IL1A (147760), and IL1B (147720), showed that serum levels were highest during the menstrual period, but there were no significant changes on the day when symptoms appeared. After ending 5 months of treatment with GnRHa, the patient had normal menstrual cycles, and although symptoms still occurred, they were mild and did not require treatment.
Yamasaki et al. (2011) described a 14-year-old Japanese girl who presented with a 1-year history of recurrent febrile episodes (39 to 41 degrees Celsius) associated with development of regular menstrual cycles. Recording of basal body temperatures revealed that the fevers occurred for 10 to 12 days, concomitant with the luteal phase of every ovulatory cycle, and disappeared 1 day before the onset of menses. Suppression of the ovulatory cycle with GnRHa abolished the fevers. Yamasaki et al. (2011) noted that unlike the report by Rutanen et al. (1993), in which there was persistent elevation of TNF and IL6 associated with progesterone action, serum levels of inflammatory cytokines in this patient, including TNF, IL1B, IL2 (147680), IL6, IL8 (146930), IL10 (124092), and C-reactive protein (123260), did not change during GnRHa therapy and most were within the normal range before and during GnRHa administration. Yamasaki et al. (2011) concluded that luteal-phase-dependent febrile episodes might be induced by various mechanisms.
Jiang et al. (2012) studied a 33-year-old Taiwanese woman with high fevers (greater than 38 degrees Celsius) in both the pre- and postovulation periods of her menstrual cycle since menarche at 14 years of age. Evaluation for infectious processes was negative, and serologic studies for connective tissue disorders and immunoelectrophoresis were all normal. During her menstrual cycles, extremely high levels of estrogen were observed in the luteal phase, and her fevers were not associated with levels of proinflammatory factors such as IL1B or IL6. GnRHa therapy resulted in complete remission of the fevers in association with ovarian suppression, and administration of a conjugated estrogen, Premarin, on the first day of the menstrual cycle immediately increased her body temperature. However, the progesterone antagonist RU486 had no effect on her fevers; taken together, these findings suggested that estrogen might play a critical role in her fevers. Family history revealed that her father had diabetes and diabetes-associated uremia, and her older brother developed migraines at age 20 years and diabetes at age 32. Her mother and sister were healthy. Because migraine, thermoregulation, and glucose metabolism are associated with human serotonin receptor HTR1A (109760) function, Jiang et al. (2012) administered a serotonin receptor antagonist, buspiron, which resulted in successful remission of the patient's periodic fevers.
Molecular Genetics
In a 33-year-old Taiwanese woman with recurrent fevers associated with her menstrual cycle that were successfully treated with a serotonin receptor antagonist, Jiang et al. (2012) sequenced the serotonin receptor gene HTR1A (109760) and identified a 1-bp deletion in the upstream promoter (-480delA; 109760.0001). The mutation was also identified in her father and brother, who had serotonin-related disorders such as diabetes and migraines, but was not found in her unaffected mother or sister or in 50 unrelated population controls. Jiang et al. (2012) proposed that increased concentrations of estrogen during the pre- and postovulation phases triggered an increase in body temperature in this patient through a failure in the negative feedback pathway of serotonin caused by HTR1A -480delA-mediated deficiency.
INHERITANCE \- Autosomal dominant GENITOURINARY Internal Genitalia (Female) \- Spontaneous abortion, recurrent (in some patients) \- Fetal loss after 6 to 7 weeks of gestation (in some patients) MUSCLE, SOFT TISSUES \- Myalgia with febrile episodes (rare) NEUROLOGIC Central Nervous System \- Tremor with febrile episodes (rare) \- Ataxia with febrile episodes (rare) \- Lower extremity weakness with febrile episodes (rare) \- Migraine (in affected males) METABOLIC FEATURES \- High fever (38-41 degrees centigrade), recurrent with each menstrual cycle \- Periodic fever, luteal phase-dependent (in some patients) \- Periodic fever, pre- and postovulation (in some patients) ENDOCRINE FEATURES \- Hypercortisolism, mild (in some patients) \- Diabetes (in affected males) IMMUNOLOGY \- TNF continuously elevated (in some patients) \- IL6 continuously elevated (in some patients) MISCELLANEOUS \- Symptoms relieved by ovarian suppression \- Symptoms relieved by progesterone antagonist (in some patients) \- Symptoms relieved by serotonin antagonist (in some patients) \- Affected males have serotonin-related disorders such as migraine headaches and diabetes MOLECULAR BASIS \- Caused by mutation in the 5-hydroxytryptamine receptor-1A gene (HTR1A, 109760.0001 ) ▲ 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
|
PERIODIC FEVER, MENSTRUAL CYCLE-DEPENDENT
|
c3553418
| 8,282 |
omim
|
https://www.omim.org/entry/614674
| 2019-09-22T15:54:33 |
{"omim": ["614674"]}
|
In a sibship of Swedish extraction, Gorlin et al. (1971) observed 2 sisters with cleft soft palate, severe oligodontia of the deciduous teeth, no permanent dentition, bilateral conductive deafness due to fixation of the footplate of the stapes, short halluces with wide space between the first and second toes, and coalition of bones in the foot. Gorlin (1989) knew of no further cases.
HEENT \- Cleft soft palate \- Severe oligodontia of deciduous teeth \- No permanent dentition \- Bilateral conductive deafness Inheritance \- Autosomal recessive Skel \- Short halluces \- Wide space between first and second toes \- Foot bone fusions ▲ 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
|
CLEFT PALATE, DEAFNESS, AND OLIGODONTIA
|
c1859081
| 8,283 |
omim
|
https://www.omim.org/entry/216300
| 2019-09-22T16:29:32 |
{"mesh": ["C565844"], "omim": ["216300"], "orphanet": ["2010"]}
|
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa with or without skeletal anomalies (RPSKA) is caused by homozygous or compound heterozygous mutation in the CWC27 gene (617170) on chromosome 5q12.
Clinical Features
Phillips et al. (1981) described a brother and sister with severe retinitis pigmentosa, short stature, and brachydactyly. Ocular examination in the second decade of life showed severely restricted visual fields and reduced or absent responses on electroretinography. Skeletal x-rays in early childhood showed metaphyseal chondrodysplasia of the proximal femoral metaphyses, whereas hip x-rays at ages 14 and 17 years appeared near-normal and normal, respectively. In addition, hand x-rays showed marked shortening of metacarpals and terminal phalanges. The sibs had IQs within the normal range. Both parents were unaffected clinically and radiologically, and there was no family history of a similar disorder.
Lorda-Sanchez et al. (1999) reported a Spanish brother and sister with RP, short stature, brachydactyly, and moderate mental retardation. Both patients developed slowly progressive visual problems after age 10 years, with night blindness and constriction of visual fields; funduscopy showed findings consistent with RP. Both sibs also showed marked brachydactyly of the hands and feet, particularly of the terminal phalanges, and exhibited craniofacial dysmorphism, including macrocephaly, malar hypoplasia, downslanting palpebral fissures, large columella, hypoplastic nares, large low-set ears, micrognathia, and short neck.
Xu et al. (2017) studied 10 patients from 7 unrelated families of diverse ethnicities, including the 2 Spanish sibs reported by Lorda-Sanchez et al. (1999), who had retinal degeneration, brachydactyly, short stature, craniofacial dysmorphism, and neurologic defects. Retinal defects were consistent with RP in most patients, in whom night blindness occurred around 10 years of age, followed by restriction of visual fields; however, 1 patient with more severe retinal defects had been diagnosed with Leber congenital amaurosis (LCA; see 204000). Brachydactyly affected primarily the distal phalanges, and some affected individuals showed hypoplastic nails. Craniofacial anomalies included frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability. Two of the probands, a 14-year-old Han Chinese boy and a 7-year-old Han Chinese girl, exhibited a retinal phenotype without syndromic features except for mild brachydactyly in the girl.
Molecular Genetics
In 7 families with retinitis pigmentosa with or without skeletal anomalies, Xu et al. (2017) performed whole-exome sequencing and identified homozygosity or compound heterozygosity for protein-truncating mutations in the CWC27 gene (see, e.g. 617170.0001-617170.0004) in all 10 affected individuals. The mutations segregated with disease in the 7 families, and either were not found or occurred only once in heterozygous state in public variant databases. Xu et al. (2017) noted that the 2 Han Chinese patients who exhibited a significantly milder extraocular phenotype shared the most C-terminal mutation (see 617170.0003), suggesting that residual CWC27 function might account for the phenotypic variability.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Macrocephaly (in some patients) \- Craniosynostosis (in 1 patient) Face \- Frontal bossing \- Micrognathia Ears \- Large ears \- Low-set ears Eyes \- Downslanting palpebral fissures \- Constriction of visual fields \- Thinning of retinal vessels \- Salt and pepper pigment changes \- Retinitis pigmentosa Nose \- Large columella \- Hypoplastic nares CARDIOVASCULAR Heart \- Ventricular septal defects (in 1 patient) Vascular \- Bilateral superior vena cava (in 1 patient) GENITOURINARY Kidneys \- Renal cysts (in 1 patient) \- Horseshoe kidney (in 1 patient) Bladder \- Bladder cyst (in 1 patient) SKELETAL Skull \- Macrocephaly (in some patients) \- Craniosynostosis (in 1 patient) Hands \- Brachydactyly \- Shortening of distal phalanges Feet \- Brachydactyly SKIN, NAILS, & HAIR Nails \- Hypoplastic nails (in some patients) NEUROLOGIC Central Nervous System \- Intellectual disability, mild to moderate \- Psychomotor retardation \- Feeding difficulties \- Speech delay \- Walking delay MISCELLANEOUS \- Phenotypic variability among families MOLECULAR BASIS \- Caused by mutation in the CWC27 spliceosome-associated cyclophilin gene (CWC27, 617170.0001 ) ▲ 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
|
RETINITIS PIGMENTOSA WITH OR WITHOUT SKELETAL ANOMALIES
|
c1855188
| 8,284 |
omim
|
https://www.omim.org/entry/250410
| 2019-09-22T16:25:23 |
{"mesh": ["C565398"], "omim": ["250410"], "orphanet": ["166035"], "synonyms": ["Alternative titles", "METAPHYSEAL CHONDRODYSPLASIA WITH RETINITIS PIGMENTOSA"]}
|
Dyssomnia
SpecialtyPsychiatry, psychology, sleep medicine
Dyssomnias are a broad classification of sleeping disorders involving difficulty getting to sleep, remaining asleep, or of excessive sleepiness.
Dyssomnias are primary disorders of initiating or maintaining sleep or of excessive sleepiness and are characterized by a disturbance in the amount, quality, or timing of sleep.
Patients may complain of difficulty getting to sleep or staying asleep, intermittent wakefulness during the night, early morning awakening, or combinations of any of these. Transient episodes are usually of little significance. Stress, caffeine, physical discomfort, daytime napping, and early bedtimes are common factors.
## Contents
* 1 Types
* 2 See also
* 3 References
* 4 External links
## Types[edit]
There are over 31 recognized kinds of dyssomnias. The major three groups, along with the group types, include:[1]:15
Intrinsic sleep disorders[1]:15
* * idiopathic hypersomnia,
* narcolepsy,
* periodic limb movement disorder,
* restless legs syndrome,
* obstructive sleep apnea,
* central sleep apnea syndrome,
* sleep state misperception,
* psychophysiologic insomnia,
* recurrent hypersomnia,
* post-traumatic hypersomnia,
* central alveolar hypoventilation syndrome,
* Extrinsic sleep disorders – 13 disorders recognized, including[1]:16
* alcohol-dependent sleep disorder,
* food allergy insomnia,
* inadequate sleep routine.
* Circadian rhythm sleep disorders, both intrinsic and extrinsic – 6 disorders recognized, including[1]:16
* advanced sleep phase syndrome,
* delayed sleep phase syndrome,
* jetlag,
* shift work sleep disorder.
## See also[edit]
* Parasomnia
* Sleep problems in women
* Somnolence
## References[edit]
1. ^ a b c d American Academy of Sleep Medicine (2001). The International Classification of Sleep Disorders, Revised (ICSD-R) (PDF). ISBN 0-9657220-1-5. Archived from the original (PDF) on 2011-07-26. Retrieved 2010-08-08.
## External links[edit]
Classification
D
* ICD-9-CM: 307.47, 780.56
* MeSH: D020920
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
* Paraphilia
* Fetishism
* Voyeurism
* Sexual maturation disorder
* Sexual relationship disorder
Other
* Factitious disorder
* Munchausen syndrome
* Intermittent explosive disorder
* Dermatillomania
* Kleptomania
* Pyromania
* Trichotillomania
* Personality disorder
Childhood and learning
Emotional and behavioral
* ADHD
* Conduct disorder
* ODD
* Emotional and behavioral disorders
* Separation anxiety disorder
* Movement disorders
* Stereotypic
* Social functioning
* DAD
* RAD
* Selective mutism
* Speech
* Stuttering
* Cluttering
* Tic disorder
* Tourette syndrome
Intellectual disability
* X-linked intellectual disability
* Lujan–Fryns syndrome
Psychological development
(developmental disabilities)
* Pervasive
* Specific
Mood (affective)
* Bipolar
* Bipolar I
* Bipolar II
* Bipolar NOS
* Cyclothymia
* Depression
* Atypical depression
* Dysthymia
* Major depressive disorder
* Melancholic depression
* Seasonal affective disorder
* Mania
Neurological and symptomatic
Autism spectrum
* Autism
* Asperger syndrome
* High-functioning autism
* PDD-NOS
* Savant syndrome
Dementia
* AIDS dementia complex
* Alzheimer's disease
* Creutzfeldt–Jakob disease
* Frontotemporal dementia
* Huntington's disease
* Mild cognitive impairment
* Parkinson's disease
* Pick's disease
* Sundowning
* Vascular dementia
* Wandering
Other
* Delirium
* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
* v
* t
* e
Sleep and sleep disorders
Stages of sleep cycles
* Rapid eye movement (REM)
* Non-rapid eye movement
* Slow-wave
Brain waves
* Alpha wave
* Beta wave
* Delta wave
* Gamma wave
* K-complex
* Mu rhythm
* PGO waves
* Sensorimotor rhythm
* Sleep spindle
* Theta wave
Sleep disorders
Dyssomnia
* Excessive daytime sleepiness
* Hypersomnia
* Insomnia
* Kleine–Levin syndrome
* Narcolepsy
* Night eating syndrome
* Nocturia
* Sleep apnea
* Catathrenia
* Central hypoventilation syndrome
* Obesity hypoventilation syndrome
* Obstructive sleep apnea
* Periodic breathing
* Sleep state misperception
Circadian rhythm
disorders
* Advanced sleep phase disorder
* Cyclic alternating pattern
* Delayed sleep phase disorder
* Irregular sleep–wake rhythm
* Jet lag
* Non-24-hour sleep–wake disorder
* Shift work sleep disorder
Parasomnia
* Bruxism
* Nightmare disorder
* Night terror
* Periodic limb movement disorder
* Rapid eye movement sleep behavior disorder
* Sleepwalking
* Somniloquy
Benign phenomena
* Dreams
* Exploding head syndrome
* Hypnic jerk
* Hypnagogia / Sleep onset
* Hypnopompic state
* Sleep paralysis
* Sleep inertia
* Somnolence
* Nocturnal clitoral tumescence
* Nocturnal penile tumescence
* Nocturnal emission
Treatment
* Sleep diary
* Sleep hygiene
* Sleep induction
* Hypnosis
* Lullaby
* Somnology
* Polysomnography
Other
* Sleep medicine
* Behavioral sleep medicine
* Sleep study
Daily life
* Bed
* Bunk bed
* Daybed
* Four-poster bed
* Futon
* Hammock
* Mattress
* Sleeping bag
* Bed bug
* Bedding
* Bedroom
* Bedtime
* Bedtime story
* Bedtime toy
* Biphasic and polyphasic sleep
* Chronotype
* Dream diary
* Microsleep
* Mouth breathing
* Nap
* Nightwear
* Power nap
* Second wind
* Siesta
* Sleep and creativity
* Sleep and learning
* Sleep deprivation / Sleep debt
* Sleeping while on duty
* Sleepover
* Snoring
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dyssomnia
|
c0700201
| 8,285 |
wikipedia
|
https://en.wikipedia.org/wiki/Dyssomnia
| 2021-01-18T18:54:20 |
{"mesh": ["D020920"], "icd-9": ["780.56", "307.47"], "wikidata": ["Q559435"]}
|
A rare primary glomerular disease characterized by the association of congenital nephrotic syndrome, early onset renal failure and ocular anomalies with microcoria and severe neurodevelopment deficits.
## Epidemiology
Less than 70 cases have been described in the literature to date.
## Clinical description
Presentation is typically with congenital microcoria and heavy proteinuria. Proteinuria is usually nephrotic range, at or shortly after birth and progresses rapidly to early onset renal failure. The histological finding is usually diffuse mesangial sclerosis characterized by small and condensed appearance of glomerulus in which mesangial region shows some collagenous tissue. Ocular anomalies are usually bilateral but may vary in severity which include microcoria, iris hypoplasia, posterior embryotoxon, megalo- or microcornea, cataract, lenticonus, persistent fetal vasculature, retinal detachment, glaucoma, and phthisis bulbi. Neurological manifestations include severe global development delay, marked muscle hypotonia, movement disorders, and blindness. It should be noted that some cases with this disease show mild phenotypes of late onset proteinuria without ocular or mental abnormalities.
## Etiology
Mutations in the LAMB2 gene (3p21) encoding laminin beta 2 have been identified. Laminin beta 2 is expressed in the glomerular basement membrane, at the neuromuscular junctions, as well as in the intraocular muscles, lens and retina.
## Differential diagnosis
Early onset severe proteinuria accompanied by ocular anomalies are rare. Therefore, in typical cases, it is relatively easy to suspect this disease. Lowe syndrome (proteinuria, mostly low molecular weight protein, and congenital cataract) or renal-coloboma syndrome (due to PAX2 gene pathogenic variants) can be candidates for differential diagnosis.
## Antenatal diagnosis
Prenatal diagnosis is difficult, but sometimes may be suspected on hyperechogenic kidneys and oligohydramnios. Only genetic testing allows early and reliable prenatal diagnosis. Prenatal diagnosis may be offered to families in which the disease-causing mutation has already been identified in affected siblings.
## Genetic counseling
The disease is transmitted as an autosomal recessive trait. Where both parents are unaffected carriers of the disease, there is a 25% risk of transmission to offspring. Carrier testing of healthy family members is possible where the mutation has been identified in a family with at least one affected member.
## Management and treatment
There is no specific treatment available. Since protein loss is limited, nephrectomy to prevent protein loss to urine is rarely needed. Angiotensin converting enzyme (ACE) inhibitors could help reduce urine protein loss and can delay the progression to end-stage kidney disease (ESKD) due to their renal protective effects. Renal replacement therapies including kidney transplantation are successfully employed. To date, there is no-evidence of disease-recurrence reported in the grafts after kidney transplantation. Careful ophthalmological follow up is required for the care of retinal detachment.
## Prognosis
The kidney prognosis is severe with most patients progressing towards renal failure within the first year of life. Visual prognosis is generally poor: visual acuity ranges from no light perception to 20/200. Mild to severe intellectual disability is always observed. Survival into adult is reported with renal replacement therapies.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pierson syndrome
|
c1836876
| 8,286 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2670
| 2021-01-23T17:26:41 |
{"gard": ["9420"], "mesh": ["C537185"], "omim": ["609049"], "umls": ["C1836876"], "icd-10": ["Q13.8"], "synonyms": ["Microcoria-congenital nephrosis syndrome"]}
|
Fissures, cracks, or linear scars in the skin associated with congenital syphilis
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Rhagades" – news · newspapers · books · scholar · JSTOR (April 2019)
For the genus of moths, see Rhagades (moth).
Rhagades are fissures, cracks, or linear scars in the skin, especially at the angles of the mouth and nose. They tend to form at areas of motion. They can be a result from bacterial infection of skin lesions. They are associated with congenital syphilis.
This is one of the late stage manifestations of congenital syphilis, others are saber shins, Hutchinson teeth, saddle nose, and Clutton's joints (usually knee synovitis).[1]
## See also[edit]
* Angular cheilitis
* Anal fissure
## References[edit]
1. ^ Nelson's Textbook of Pediatrics. p. 1472.
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
|
Rhagades
|
c0221245
| 8,287 |
wikipedia
|
https://en.wikipedia.org/wiki/Rhagades
| 2021-01-18T19:05:38 |
{"wikidata": ["Q1931684"]}
|
Jackhammer esophagus is a motility disorder of the esophagus, the tube that connects the mouth with the stomach, classified under esophageal spasms. Esophageal spasms are divided in 2 main types, diffuse esophageal spasm and hypertensive peristalsis or nutcracker esophagus. Jackhammer esophagus is the most serious manifestation of the hypertensive type and it is also known as hypercontractile peristalsis. Contractions (spasms) are very intensive (very high amplitude), involve most of the esophagus, and last for a long time. There is a jackhammer-type appearance on the high-resolution manometry, an exam which measures the muscle contractions that occur in the esophagus when swallowing. Symptoms may include feeding difficulty (dysphagia) and chest pain that might be confused with a heart attack.The cause is unknown but it may occur with, or as a consequence of, other conditions, especially gastroesophageal reflux disease (GERD). Treatment depends on the frequency and severity of the esophageal spasms. It may include medication, Botox injections, and surgical procedures. Very hot or cold liquids, loud noises, and stress may worsen dysphagia. Jackhammer esophagus can progress to achalasia, a rare and serious condition that makes it very difficult for food and liquid to pass into the stomach.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Jackhammer esophagus
|
None
| 8,288 |
gard
|
https://rarediseases.info.nih.gov/diseases/13455/jackhammer-esophagus
| 2021-01-18T17:59:42 |
{"synonyms": ["Hypercontractile esophagus"]}
|
A number sign (#) is used with this entry because of evidence that autosomal dominant limb-girdle muscular dystrophy-4 (LGMDD4) is caused by heterozygous mutation in the CAPN3 gene (114240) on chromosome 15q15.
Biallelic mutation in the CAPN3 gene can cause autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1; 253600), which has earlier onset and is in general a more severe disorder.
Description
Autosomal dominant limb-girdle muscular dystrophy-4 is characterized by onset of proximal muscle weakness in young adulthood. Affected individuals often have gait difficulties; some may have upper limb involvement. Other features include variably increased serum creatine kinase, myalgia, and back pain. The severity and expressivity of the disorder is highly variable, even within families (summary by Vissing et al., 2016).
For a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see 603511.
Nomenclature
At the 229th ENMC international workshop, Straub et al. (2018) reviewed, reclassified, and/or renamed forms of LGMD. The proposed naming formula was 'LGMD, inheritance (R or D), order of discovery (number), affected protein.' Under this formula, LGMD1I was renamed LGMDD4.
Clinical Features
Vissing et al. (2016) reported 37 individuals from 10 unrelated families of northern European descent with limb-girdle muscular dystrophy. The phenotype and severity were highly variable, even within families. Most patients had symptom onset as adults (average 34 years), although a few patients had onset in the first or second decade. Features included proximal muscle weakness and atrophy of the upper and lower limbs. Most patients remained ambulatory, but 3 were wheelchair-bound. Patients had a common pattern of muscle involvement, including the paraspinal, gluteal, hamstring, and medial gastrocnemius, which was confirmed by fatty replacement of muscle tissue in these muscles on imaging. Serum creatine kinase was elevated in most, but not all, patients, and muscle biopsy, when performed, showed myopathic changes, including increased internal nuclei, variation in fiber size, and occasional fibrosis. Additional features included back pain and myalgia. Overall, the disorder was similar to LGMDR1, but was less severe. Several mutation carriers were clinically asymptomatic, but showed subtle signs of the disorder, such as increased serum creatine kinase or muscle atrophy.
Martinez-Thompson et al. (2018) reported 3 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy. Two of the families were multigenerational and very large. Clinical features of the 3 probands were described in detail. The patients had onset of proximal muscle weakness mainly affecting the lower limbs between 20 and 50 years of age. They had back pain, hyperlordosis, myalgia, and gait abnormalities due to proximal muscle weakness. Other features included scapular winging and weakness of the abdominal wall. Physical examination and/or imaging showed atrophy and fatty replacement of the iliopsoas, gluteus, and paraspinal muscles. EMG studies showed a myopathic pattern, and patients had variably increased serum creatine kinase. Muscle biopsy showed mild chronic myopathic changes, such as fiber splitting, some internal nuclei, type 1 fiber predominance, and rare regenerating fibers.
Inheritance
The transmission pattern of limb-girdle muscular dystrophy in the families reported by Vissing et al. (2016) was consistent with autosomal dominant inheritance.
Molecular Genetics
In 36 patients from 10 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy type 1I, Vissing et al. (2016) identified a heterozygous in-frame 21-bp deletion (c.643_663del21) in the CAPN3 gene (114240.0011). The families were identified from several different neuromuscular centers in northern Europe. Haplotype analysis of 4 families indicated a founder effect. Analysis of several patients' muscle tissue showed normal mRNA levels and no evidence of nonsense-mediated mRNA decay, but significantly decreased CAPN3 protein levels, at less than 15% of control values. Vissing et al. (2016) postulated that the in-frame nature of the mutation may have led to expression of a mutated protein which could have a dominant-negative effect.
In 3 unrelated patients of northern European descent with LGMDD4, Martinez-Thompson et al. (2018) identified the same heterozygous 21-bp deletion in the CAPN3 gene that had been reported by Vissing et al. (2016). The deletion resulted in the deletion of residues Ser215_Gly221 in the first structural domain. The mutations were found by next-generation, whole-exome, or Sanger sequencing; all were confirmed by Sanger sequencing. Each proband had a family history of the disorder, although not all affected family members were available for genetic testing. Functional studies of the variant were not performed, but Western blot analysis of patient tissues showed greatly decreased amounts of the CAPN3 protein.
INHERITANCE \- Autosomal dominant CHEST Ribs Sternum Clavicles & Scapulae \- Scapular winging SKELETAL Spine \- Hyperlordosis \- Back pain MUSCLE, SOFT TISSUES \- Muscle weakness, proximal \- Muscle atrophy, proximal \- Myalgia \- Lower limbs more affected than upper limbs \- Atrophy of the paraspinal muscles \- Atrophy of the gluteal muscles \- Atrophy of the hamstrings \- Fatty replacement of affected muscles \- Abdominal wall muscle weakness \- Myopathic changes seen on EMG \- Myopathic changes, mild, seen on skeletal muscle biopsy \- Increased internal nuclei \- Variation in fiber size \- Fiber splitting \- Type 1 fiber predominance NEUROLOGIC Central Nervous System \- Gait difficulties LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Adult onset (average 37 years) \- Some mutation carriers may be asymptomatic \- Some patients may become wheelchair-bound \- Reported in families of Northern European descent who share the same mutation MOLECULAR BASIS \- Caused by mutation in the calpain 3 gene (CAPN3, 114240.0011 ) ▲ 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
|
MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 4
|
c1869123
| 8,289 |
omim
|
https://www.omim.org/entry/618129
| 2019-09-22T15:43:50 |
{"mesh": ["C535895"], "omim": ["618129"], "orphanet": ["267"], "synonyms": ["Alternative titles", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1I"]}
|
Splenic tumor
SpecialtyOncology
A splenic tumor is a rare form of tumor that may be malignant or benign. Malignant forms include lymphoma and sarcoma.[1]
Lymphoma is the most common malignant splenic tumor.[2]
## References[edit]
1. ^ Bisset (1 January 2008). Differential Diagnosis in Abdominal Ultrasound, 3/e. Elsevier India. pp. 208–. ISBN 978-81-312-1574-6. Retrieved 22 May 2011.
2. ^ Neal C. Dalrymple; John R. Leyendecker; Michael Oliphant (12 June 2009). Problem Solving in Abdominal Imaging. Elsevier Health Sciences. pp. 410–. ISBN 978-0-323-04353-3. Retrieved 22 May 2011.
## External links[edit]
Classification
D
* ICD-10: C26.1, D13.9
* MeSH: D013160
* v
* t
* e
Lymphatic disease: organ and vessel diseases
Thymus
* Abscess
* Hyperplasia
* Hypoplasia
* DiGeorge syndrome
* Ectopic thymus
* Thymoma
* Thymic carcinoma
Spleen
* Asplenia
* Asplenia with cardiovascular anomalies
* Accessory spleen
* Polysplenia
* Wandering spleen
* Splenomegaly
* Banti's syndrome
* Splenic infarction
* Splenic tumor
Lymph node
* Lymphadenopathy
* Generalized lymphadenopathy
* Castleman's disease
* Intranodal palisaded myofibroblastoma
* Kikuchi disease
* Tonsils
* see Template:Respiratory pathology
Lymphatic vessels
* Lymphangitis
* Lymphangiectasia
* Lymphedema
* Primary lymphedema
* Congenital lymphedema
* Lymphedema praecox
* Lymphedema tarda
* Lymphedema–distichiasis syndrome
* Milroy's disease
* Secondary lymphedema
* Bullous lymphedema
* Factitial lymphedema
* Postinflammatory lymphedema
* Postmastectomy lymphangiosarcoma
* Waldmann disease
This oncology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Splenic tumor
|
c0037999
| 8,290 |
wikipedia
|
https://en.wikipedia.org/wiki/Splenic_tumor
| 2021-01-18T18:33:04 |
{"mesh": ["D013160"], "umls": ["C0037999"], "icd-10": ["C26.1"], "wikidata": ["Q7578547"]}
|
Binder syndrome is a rare developmental anomaly, affecting primarily the anterior part of the maxilla and nasal complex.
## Epidemiology
Binder syndrome occurs in less than one birth in 10,000 but is probably underdiagnosed.
## Clinical description
Affected individuals typically have an unusually flat, underdeveloped midface (midfacial hypoplasia), with an abnormally short nose and flat nasal bridge, underdeveloped upper jaw, relatively protruding lower jaw and/or a 'reverse overbite'' (or class III malocclusion). Hypoplasia of distal phalanges of fingers was reported in some cases.
## Etiology
The etiology and pathogenesis of Binder syndrome remains uncertain.
## Differential diagnosis
Phenocopies of Binder syndrome have been described in children exposed in utero to phenytoin or to vitamin K deficiency, being induced either by drug (anticoagulants) or by biliary lithiasis. Some authors consider Binder syndrome as an allelic form of chondrodysplasia punctata. Others suggest that Binder type maxillonasal dysplasia does not represent a distinct disease entity or syndrome, but rather is a nonspecific abnormality of the nasomaxillary regions.
## Antenatal diagnosis
Prenatal diagnosis by two and three-dimensional ultrasound is possible (visualization of flat profile; bone hypoplasia) from 20-22 weeks of gestation.
## Genetic counseling
Most reported cases were sporadic. A few cases of recurrence in pedigrees could be explained by either autosomal recessive or dominant inheritance with reduced penetrance or by multifactorial etiology.
## Management and treatment
Since the degree of malformation in Binder syndrome varies significantly, surgical correction (orthodontic, plastic surgery) needs to be tailored individually.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Maxillonasal dysplasia
|
c0220692
| 8,291 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1248
| 2021-01-23T18:50:35 |
{"gard": ["6992"], "mesh": ["C536036"], "omim": ["155050"], "umls": ["C0220692", "C3888567"], "icd-10": ["Q75.8"], "synonyms": ["Binder syndrome", "Maxillonasal dysostosis"]}
|
Payling-Wright and Evans (1970) described a girl who had been normal until age 3 months when there was onset of seizures. At the age of 9 months, she was floppy; also, she made choreoathetotic movements and appeared to lack sight or hearing. Investigations showed small head, hypsarrhythmia by EEG, and dilated ventricles by air encephalography. Lymphocytes grown in short-term culture showed very low beta-xylosidase. Thus, this appears to be a lysosomal disorder. No further information is available (Evans, 1974).
Eyes \- Blindness Radiology \- Dilated ventricles by air encephalography Neuro \- Seizures \- Hypotonia \- Choreoathetosis Inheritance \- Autosomal recessive Head \- Microcephaly Lab \- Hypsarrhythmia by EEG \- Very low beta-xylosidase in short-term lymphocyte culture Ears \- Deafness ▲ 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
|
XYLOSIDASE DEFICIENCY
|
c1848407
| 8,292 |
omim
|
https://www.omim.org/entry/278900
| 2019-09-22T16:21:05 |
{"mesh": ["C564730"], "omim": ["278900"]}
|
Neurothekeoma histology slide
Neurothekeoma is a benign cutaneous tumor first described by Gallager and Helwig, who proposed the term in order to reflect the presumed origin of the lesion from nerve sheath.[1] Microscopically, the lesions described closely resembled the tumor, "nerve sheath myxoma", an entity first described by Harkin and Reed.[2] The latter had, through the years, been variously described as "Bizarre cutaneous neurofibroma",[3] "Myxoma of nerve sheath",[3] and "Pacinian neurofibroma".[3]
Clinically, neurothekeomas present as a solitary nodule of the skin.[4] The most common sites of occurrence are the head and neck and the extremities.[4] The lesions range in size from about 0.5 cm. to more than 3 cm.[4] The average patient age is about 25 years, but neurothkeomas may occur at any age.[4] Women are affected about more often; the male to female ratio is approximately 1:2.[4]
Microscopically, neurothekeoma consists of closely aggregated bundles or fascicles of spindle-shaped cells.[5] The fascicles may or may not have a myxoid background.[5]
Since the time of their first description, it has been reported that neurothekeomas are likely not of nerve sheath origin, as implied by the term.[4] Consequently, neurothekeoma and nerve sheath myxoma are likely not related histogenetically, although they are similar in appearance and in behavior.[4]
## See also[edit]
* List of cutaneous conditions
* List of histologic stains that aid in diagnosis of cutaneous conditions
* Myxoid tumor
## References[edit]
1. ^ Gallager RL, Helwig EB (December 1980). "Neurothekeoma-a benign cutaneous tumor of neural origin". American Journal of Clinical Pathology. 74 (6): 759–764. doi:10.1093/ajcp/74.6.759. PMID 7446487.
2. ^ Harkin, James C.; Richard J. Reed (1969), Tumors of the Peripheral Nervous System, in Armed Forces Institute of Pathology, ed: Atlas of Tumor Pathology, 2nd series, fascicle 3, Washington, D.C.: Armed Forces Institute of Pathology
3. ^ a b c Pulitzer DR, Reed RJ (October 1985). "Nerve-sheath myxoma (perineurial myxoma)". American Journal of Dermatopathology. 7 (5): 407–421. PMID 4091218.
4. ^ a b c d e f g Fetsch JF, Laskin WB, Hallman JR, Lupton GP, Miettinen M (July 2007). "Neurothekeoma: an analysis of 178 tumors with detailed immunohistochemical data and long-term patient follow-up information". American Journal of Surgical Pathology. 31 (7): 1103–1114. doi:10.1097/pas.0b013e31802d96af. PMID 17592278.
5. ^ a b Reed, Richard J.; Pulitzer, Donald R. (2008), "Chapter 35: Tumors of Neural Tissue", in Elder D; et al. (eds.), Lever's Histopathology of the Skin (Ninth ed.), Philadelphia: Lippincott Raven, ISBN 978-0781773638
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Neurothekeoma
|
c0206730
| 8,293 |
wikipedia
|
https://en.wikipedia.org/wiki/Neurothekeoma
| 2021-01-18T18:34:37 |
{"mesh": ["D018321"], "umls": ["C0206730"], "wikidata": ["Q7002720"]}
|
Aneurysm of heart
Heart left ventricular aneurysm short axis view
Ventricular aneurysms are one of the many complications that may occur after a heart attack. The word aneurysm refers to a bulge or ‘pocketing’ of the wall or lining of a vessel commonly occurring in the blood vessels at the base of the septum, or within the aorta. In the heart, they usually arise from a patch of weakened tissue in a ventricular wall, which swells into a bubble filled with blood.[1] This, in turn, may block the passageways leading out of the heart, leading to severely constricted blood flow to the body. Ventricular aneurysms can be fatal. They are usually non-rupturing because they are lined by scar tissue.
A left ventricular aneurysm can be associated with ST elevation.[2]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 Cardiac Diverticulum
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
Ventricular aneurysms usually grow at a very slow pace, but can still pose problems. Usually this type of aneurysm grows in the left ventricle. This bubble has the potential to block blood flow to the rest of the body, and thus limit the patient's stamina. In other cases, a similarly developed pseudoaneurysm ("false aneurysm") may burst, sometimes resulting in the death of the patient. Also, blood clots may form on the inside of ventricular aneurysms, and form embolisms. If such a clot escapes from the aneurysm, it will be moved in the circulation throughout the body. If it gets stuck inside a blood vessel, it may cause ischemia in a limb, a painful condition that can lead to reduced movement and tissue death in the limb.[1] Alternatively, if a clot blocks a vessel going to the brain, it can cause a stroke. In certain cases, ventricular aneurysms cause ventricular failure or arrythmia. At this stage, treatment is necessary.
## Causes[edit]
Ventricular aneurysms are usually complications resulting from a heart attack. When the heart muscle (cardiac muscle) partially dies during a heart attack, a layer of muscle may survive, and, being severely weakened, start to become an aneurysm. Blood may flow into the surrounding dead muscle and inflate the weakened flap of muscle into a bubble. It may also be congenital.
## Diagnosis[edit]
Left ventricular aneurysm
An ECG of a person with a left ventricular aneurysm. Note the ST elevation in the anterior leads.
When a person visits the hospital or doctor with other symptoms, especially with a history of heart problems, they will normally be required to undergo an electrocardiogram, which monitors electrical activity within the heart and shows abnormalities when a cardiac aneurysm is present. It can also appear as a bulge on a chest x-ray, and a more accurate diagnosis will then be made using an echocardiogram, which uses ultrasound to ‘photograph’ the heart and how it functions while it beats.t
* Play media
Left ventricular aneurysm as seen on ultrasound[3]
* Play media
Left ventricular aneurysm as seen on ultrasound[3]
### Differential diagnosis[edit]
It should also not be confused with a pseudoaneurysm,[4][5] coronary artery aneurysm or a myocardial rupture (which involves a hole in the wall, not just a bulge.)
## Treatment[edit]
Some people live with this type of aneurysm for many years without any specific treatment. Treatment is limited to surgery (ventricular reduction) for this defect of the heart. However, surgery is not required in most cases but, limiting the patient's physical activity levels to lower the risk of making the aneurysm bigger is advised. Also ACE Inhibitors seem to prevent Left Ventricular remodeling and aneurysm formation.
Blood thinning agents may be given to help reduce the likelihood of blood thickening and clots forming, along with the use of drugs to correct the irregular rhythm of the heart (seen on the electrocardiogram)
## Cardiac Diverticulum[edit]
Cardiac diverticulum or ventricular diverticulum is defined as a congenital malformation of the fibrous or muscular part of the heart which is only visible during chest x-rays or during an echocardiogram reading.[6] This should not be confused with ventricular diverticulum, as the latter is a sub type derived from the latter in congenital cases. it is usually asymptomatic and is only detected using imaging. Fibrous diverticulum is characterised by a calcification if present at the tip ( apex) or a thrombi that may detaches to form an emboli. Muscular diverticulum is characterised by appendix forming at the ether of the ventricles.[7] it is a rare anomaly and can be diagnosed prenatal. Diagnosis is usually done by a chest X-ray and silhouette is viewed around the heart. Echocardiogram reading present a similar picture to ventricular aneurysms on the ST segment. Management is dependent on the situation presented and the severity of the case. Usually surgical resection is advised but in prenatal cases, due to combination with other cardiac abnormalities, especially in latter trimesters, but pericardiocentesis is useful technique to reduce pleural effusion or/ and secondary disorders.
## See also[edit]
* Coronary artery aneurysm
## References[edit]
1. ^ a b "What is an Aneurysm?". www.heart.org. Retrieved 14 March 2017.
2. ^ Victor F. Froelicher; Jonathan Myers (2006). Exercise and the heart. Elsevier Health Sciences. pp. 138–. ISBN 978-1-4160-0311-3. Retrieved 10 October 2010.
3. ^ a b "UOTW #57 - Ultrasound of the Week". Ultrasound of the Week. 29 August 2015. Retrieved 27 May 2017.
4. ^ Zoffoli G, Mangino D, Venturini A, et al. (February 2009). "Diagnosing left ventricular aneurysm from pseudo-aneurysm: a case report and a review in literature". J Cardiothorac Surg. 4 (1): 11. doi:10.1186/1749-8090-4-11. PMC 2654444. PMID 19239694.
5. ^ Brown SL, Gropler RJ, Harris KM (May 1997). "Distinguishing left ventricular aneurysm from pseudoaneurysm. A review of the literature". Chest. 111 (5): 1403–9. doi:10.1378/chest.111.5.1403. PMID 9149600.
6. ^ Mady, Charles (1982). "Left Ventricular Diverticulum: Analysis of Two Operated Cases and Review of the Literature". Angiology. 33 (4): 280–286. doi:10.1177/000331978203300409. ISSN 0003-3197. PMID 7073021.
7. ^ Garcia Rodriguez, Raquel; Rodriguez Guedes, Azahara; Garcia Delgado, Raquel; Roldan Gutierrez, Lourdes; Medina Castellano, Margarita; Garcia Hernandez, Jose Angel (2015). "Prenatal Diagnosis of Cardiac Diverticulum with Pericardial Effusion in the First Trimester of Pregnancy with Resolution after Early Pericardiocentesis". Case Reports in Obstetrics and Gynecology. 2015: 1–11. doi:10.1155/2015/154690. ISSN 2090-6684. PMID 26558121.
## Further reading[edit]
* Graber, J.D.; Oakley, C.M.; Pickering, B.N.; Goodwin, J.F.; Raphael, M.J.; Steiner, R.E. (1972). "Ventricular aneurysm. An appraisal of diagnosis and surgical treatment". British Heart Journal. PubMed. 34 (8): 831–838. doi:10.1136/hrt.34.8.831. PMC 486989. PMID 5070115.
* Alenghat, FJ; Couper, GC; Givertz, MM (2013). "Giant left ventricular aneurysm as a late complication of inferior myocardial infarction". European Heart Journal. 24 (5): 344. doi:10.1093/eurheartj/ehs357. PMID 23095983.
## External links[edit]
Classification
D
* ICD-10: I25.3
* ICD-9-CM: 414.1
* MeSH: D006322
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ventricular aneurysm
|
c0392464
| 8,294 |
wikipedia
|
https://en.wikipedia.org/wiki/Ventricular_aneurysm
| 2021-01-18T18:48:21 |
{"umls": ["C0392464"], "icd-10": ["I25.3"], "wikidata": ["Q7920313"]}
|
Eruptive vellus hair cysts (or EVHC) are small lesions that occur most often in the chest wall, abdomen and extremities, often with a crusted surface.[1][2]:680 EVHC may occur randomly, or it can be inherited as an autosomal dominant trait. The condition affects males and females equally, and sporadic cases usually appear at 4–18 years of age. The cysts appear similar clinically to steatocystoma multiplex, as well as acneiform eruptions and milia. Therapeutic techniques that are safe and effective are rare, with incision and drainage being the primary form of treatment when sporadic regression does not occur.[3] It was first described in 1977.[4]
## Contents
* 1 Signs/symptoms
* 2 Cause
* 3 Diagnosis
* 3.1 Associations
* 4 Treatment
* 5 See also
* 6 References
* 7 Further reading
## Signs/symptoms[edit]
This section is empty. You can help by adding to it. (March 2017)
## Cause[edit]
This section is empty. You can help by adding to it. (March 2017)
## Diagnosis[edit]
Histopathology is the basis of diagnosis. Stratified-squamous epithelium with a granular layer that surrounding a cystic space filled with laminated keratin and a variable number of vellus hair cysts is seen to be present.[4] It can be difficult to distinguish from other skin conditions, including molluscum contagiosum and acne vulgaris but can be corroborated with histopathology.[5]
### Associations[edit]
It can be associated with Steatocystoma multiplex.[4]
## Treatment[edit]
The primary indication for treatment is cosmesis. Retinoids, surgery, and lasers are used as treatment modalities.[4]
## See also[edit]
* Steatocystoma simplex
* Milia
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1685. ISBN 1-4160-2999-0.
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
3. ^ Baums K, Blume-Peytavi U, Dippel E, Goerdt S, Orfanos CE (August 2000). "Guess what! Eruptive vellus hair cysts". Eur J Dermatol. 10 (6): 487–9. PMID 10980478. Retrieved 2009-03-17.
4. ^ a b c d Patel, U; Terushkin, V; Fischer, M; Kamino, H; Patel, R (Dec 15, 2012). "Eruptive vellus hair cysts". Dermatology Online Journal. 18 (12): 7. PMID 23286797.
5. ^ Alfaro-Castellón, Patricia; Mejía-Rodríguez, Silvia Anett; Valencia-Herrera, Adriana; Ramírez, Susana; Mena-Cedillos, Carlos (1 November 2012). "Dermoscopy Distinction of Eruptive Vellus Hair Cysts with Molluscum Contagiosum and Acne Lesions". Pediatric Dermatology. 29 (6): 772–773. doi:10.1111/j.1525-1470.2012.01771.x. PMID 22639880.
## Further reading[edit]
* Torchia, Daniele; Vega, Janelle; Schachner, Lawrence A. (1 February 2012). "Eruptive Vellus Hair Cysts". American Journal of Clinical Dermatology. 13 (1): 19–28. doi:10.2165/11589050-000000000-00000. PMID 21958358.
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Eruptive vellus hair cyst
|
c0345998
| 8,295 |
wikipedia
|
https://en.wikipedia.org/wiki/Eruptive_vellus_hair_cyst
| 2021-01-18T19:00:50 |
{"umls": ["C0345998"], "wikidata": ["Q5395978"]}
|
Spasmus nutans (SN) is a rare eye disease characterized by the clinical triad of asymmetric and pendular nystagmus, head nodding, and torticollis.
## Epidemiology
The prevalence of SN is unknown.
## Clinical description
The age of disease onset ranges from 4-12 months and clinically, SN is characterized by a triad of signs which are nystagmus, head nodding, and abnormal head turn or tilt (torticollis). The nystagmus in SN is typically pendular, intermittent, of small-amplitude, high frequency oscillations (shimmering nystagmus) and is usually bilateral, but it can be monocular, asymmetric, and variable in different positions of gaze. Head nodding is not always present, and often follows the onset of nystagmus. It is usually intermittent and of lower frequency than the nystagmus. Both nystagmus and head nodding can occur in any plane (horizontal (more frequent), vertical, oblique, or torsional). Strabismus and amblyopia may be present while oscillopsia is absent. Optic nerve, retinal, or intracranial abnormalities are generally absent.
## Etiology
SN is an idiopathic disorder. Head nodding suppresses nystagmus through the vestibular-ocular reflex and aids vision. Similarly, the torticollis has been observed clinically and by electrooculography (EOG) recordings to dampen nystagmus by a hypothesized vestibular mechanism. Low socioeconomic status represents a risk factor for the development of SN.
## Diagnostic methods
The diagnosis relies on exclusion of neurological and ophthalmological diseases. Eye movement recordings reveal a fine, high frequency, pendular horizontal nystagmus, which cannot be seen superimposed upon the normal optokinetic response. Visual acuities are generally lower in the eye with the greater nystagmus and vary between 6/6 and 6/24. Optic disc examinations are usually normal. Visual electrophysiology (visual evoked potential (VEP) and electroretinograms (ERG)) should be performed to exclude retinal diseases which can mimic SN.
## Differential diagnosis
Differential diagnosis includes SN-like nystagmus, which is defined as a condition where children have nystagmus, head nodding and abnormal head position similar to SN but symptoms are associated with low vision (for example optic nerve hypoplasia, achromatopsia, congenital stationary night blindness, Bardet-Biedl syndrome), neurologic diseases (optic pathway glioma (chiasmal), arachnoid cyst, opsoclonus-myoclonus syndrome, diencephalic syndrome, and Leigh syndrome (see these terms), or systemic abnormalities. Nystagmus may also be associated with idiopathic infantile nystagmus (see this term). SN may also be misdiagnosed as thalamic neoplasm and empty sella.
## Genetic counseling
SN is generally sporadic but cases of SN occurring in monozygotic twins have been reported.
## Management and treatment
No cure exists and treatment is mainly supportive. This includes treatment for strabismus, amblyopia and refractive errors.
## Prognosis
SN is a benign eye motility disorder where patients are usually healthy. The nystagmus has a tendency to decrease in intensity with age and symptoms tend to spontaneously remit within 1 to 5 years of onset with fine, residual nystagmus detectable only on eye movement recording. However, in rare cases, the signs may persist for as long as 8 years.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spasmus nutans
|
c1527306
| 8,296 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=279882
| 2021-01-23T17:03:43 |
{"mesh": ["D013036"], "umls": ["C1527306"], "icd-10": ["F98.4"]}
|
Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome is a rare, inherited cancer-predisposing syndrome characterized by an early development of cutaneous telangiectasia, mild dental and nail anomalies, patchy alopecia over the affected skin areas and increased lifetime risk for oropharyngeal cancer. Other types of cancer have also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome
|
c3281203
| 8,297 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=313846
| 2021-01-23T18:59:15 |
{"omim": ["614564"]}
|
Dendrophilia (or less often arborphilia or dendrophily) literally means "love of trees". The term may sometimes refer to a paraphilia in which people are sexually attracted to or sexually aroused by trees. This may involve sexual contact or veneration as phallic symbols or both.[1]
## References[edit]
1. ^ Corsini, Raymond J. (1999). The Dictionary of Psychology. Psychology Press. p. 263. ISBN 1-58391-028-X.
* 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
This sexuality-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dendrophilia (paraphilia)
|
None
| 8,298 |
wikipedia
|
https://en.wikipedia.org/wiki/Dendrophilia_(paraphilia)
| 2021-01-18T19:09:44 |
{"wikidata": ["Q1262499"]}
|
For a phenotypic description and a discussion of genetic heterogeneity of osteoarthritis, see OS1 (165720).
Clinical Features
Meulenbelt et al. (2006) studied families with dominant inheritance of generalized osteoarthritis in a genomewide scan. The phenotype was characterized by distinct progressive osteoarthritis in the absence of chondrodysplasia. Symptoms and radiographic osteoarthritis occurred at multiple joint sites simultaneously, including involvement of the hands with noduli, knees, hips, ankle, and spine. Individuals with clinical and radiographic evidence of osteoarthritis in 2 or more joints before the age of 50 years were considered affected. The mean age of onset in these patients was 33 years and ranged between 20 and 50 years. Family 1, with a phenotype representative of that of the other families, had been described by Meulenbelt et al. (1997).
Mapping
Meulenbelt et al. (2006) performed linkage analysis in 6 families with early-onset symptomatic osteoarthritis occurring without detectable dysplasia at multiple joint sites simultaneously in an autosomal dominant inheritance pattern. Significant linkage was found on chromosome 2q33.3 with a maximum 2-point lod score of 6.05 at marker D2S155 (theta = 0.0); the highest multipoint nonparametric linkage score was 4.70 at marker D2S2358 (p = 0.0013). Haplotype analysis of affected family members defined a minimum candidate region of 2.6 Mb between D2S1384 and D2S2178. Meulenbelt et al. (2006) investigated 2 likely candidate genes, PTHR2 (601469) and FZD5 (601723). No segregating variant was found for FZD5; a missense variant in PTHR2 that cosegregated with disease in 1 family was identified, but Meulenbelt et al. (2006) stated that it was unlikely to be the major disease gene for the observed linkage to the osteoarthritis phenotype.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
OSTEOARTHRITIS SUSCEPTIBILITY 4
|
c1835815
| 8,299 |
omim
|
https://www.omim.org/entry/610839
| 2019-09-22T16:04:07 |
{"omim": ["610839"], "synonyms": ["Alternative titles", "OSTEOARTHRITIS, GENERALIZED, WITHOUT DYSPLASIA"]}
|
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