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Angelman syndrome (happy puppet syndrome)

Genetics: 1) genetically heterogeneous group 2) most cases are sporadic but familial cases have been reported [1] 3) 60-70% of cases are due to an interstitial deletion on the maternally inherited chromosome 15 in the region q11-q13* 4) rare cases result from paternal disomy 5) in 30% of patients, neither maternal inherited deletion, nor paternal disomy, can be found a) recurrence risk for siblings is high b) molecular mechanisms are not completely known 6) associated with defects in MECP 7) associated with defects in ATP10A Clinical manifestations: 1) severe mental retardation 2) easily provoked laughter 3) ataxia 4) absent speech 5) seizures Laboratory: - UBE3A gene mutation Notes: - the Prader-Willi syndrome (PWS) & the Angelman syndrome (AS) are 2 clinically distinct disorders caused by a differential parental origin of chromosome 15q11-q13 deletions. - both also can result from uniparental disomy (inheritance of both copies of chromosome 15 from only one parent) - loss of the paternal copy of 15q11-q13, whether by deletion or maternal uniparental disomy, leads to PWS, whereas a maternal deletion or paternal uniparental disomy leads to AS. - differential modification in expression of certain mammalian genes dependent upon parental origin is known as genomic imprinting, & AS & PWS represent the best examples of this phenomenon in humans - although molecular mechanisms of genomic imprinting are unknown, DNA methylation has been proposed to play a role in the imprinting process.

Related

Prader-Willi/Angelman syndrome genotyping

Specific

Angelman syndrome/UBE3A

General

genetic disease of the central nervous system genetic syndrome (multisystem disorder)

Database Correlations

OMIM correlations

References

  1. Moncla et al Archives de Pediatrie 1(12):1118-26, 1994
  2. Saitoh Am J Med Genetics 52(2):158-63, 1994
  3. NINDS Angelman Syndrome Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Angelman-Syndrome-Information-Page
  4. ARUP Consult: Angelman Syndrome and Prader-Willi Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/prader-willi-syndrome - Angelman Syndrome and Prader-Willi Syndrome Testing https://arupconsult.com/ati/angelman-syndrome-and-prader-willi-syndrome-testing