Angelman syndrome (happy puppet syndrome)

^[1]^[2]^[3]^[4]

Genetics

genetically heterogeneous group
most cases are sporadic but familial cases have been reported^[1]
60-70% of cases are due to an interstitial deletion on the maternally inherited chromosome 15 in the region q11-q13*
rare cases result from paternal disomy
in 30% of patients, neither maternal inherited deletion, nor paternal disomy, can be found
- recurrence risk for siblings is high
- molecular mechanisms are not completely known
associated with defects in MECP
associated with defects in ATP10A

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.

↑ ^1.0 ^1.1 Moncla et al Archives de Pediatrie 1(12):1118-26, 1994
↑ Saitoh Am J Med Genetics 52(2):158-63, 1994
↑ NINDS Angelman Syndrome Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Angelman-Syndrome-Information-Page
↑ 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