Last update: 12/12/2007

Background to disease

OMIM #176270 (gene OMIM #182279)

Prader-Willi Syndrome (PWS) is an imprinting disorder caused by the loss of function of the paternally inherited region at 15q11-q13. The clinical features of PWS are infantile hypotonia, mental retardation, hypogonadism, obesity and short stature. PWS is closely linked to but distinct from, Angelman Syndrome (see separate page) as mutations in the same region also cause this disease (some of the testing analysis is mutually exclusive for both diseases).

Incidence is approximately 1 in 25-30,000.

The disorder is caused by:

1. Microdeletions – deletion of the paternally derived region (15q11-q13) account for 65-75%

of PWS cases.

2. Uniparental disomy (UPD) – maternal UPD (no paternal chromosome) accounts for 20-30% of PWS cases.

3. Imprinting defects – where the paternal chromosome had a maternal imprint, accounts for 5% PWS cases.

4. Balanced translocations – very rare and account for 0.1% cases.

Mutation type is important as recurrence risks for deletion or UPD are very low but up to 50% for imprinting mutations.

Laboratory Analysis

Analysis for this disease is now carried out by the Northern Genetics Laboratories under a reciprocal arrangement (GENLYNC). Please contact them directly regarding information regarding turnaround time and sensitivity. Local samples should still be sent via the Yorkshire Regional Genetic Laboratory where they will be forwarded as whole blood as appropriate. DNA from these samples can be stored in the Yorkshire Regional Genetic Laboratory if it is anticipated that future tests may be required (please indicate clearly on referral card if required).