Prader-Willi
Syndrome (PWS) is an imprinted
genetic disease first
described in
1956 by
Prader et al.
Clinical Features
The syndrome is
characterized by decreased
fetal activity and feeding difficulties,
obesity,
mental retardation, short
stature, and small
hands and
feet. PWS
patients typically have an
insatiable hunger, which results in the
aforementioned obesity, as well as
alimentary diabetes, which typically occurs around the onset of
puberty. These two conditions lead to a greatly decreased
life expectancy for PWS patients, though with controlled diet, sufferers can live as long as a
normal person.
Molecular Diagnosis
Prader-Willi
syndrome is
inherited in a
dominant fashion, with
paternal chromosome 15 being
responsible for the disease phenotype. The actual method of
transmission is not the standard
dominant gene paradigm. This disease is one of a small class in which
paternal imprinting is responsible (similar to
Angelman Syndrome), and as a result, has several possible
genotypes that result in the same disease. The most common is a
deletion or
rearrangement on the long arm of paternal
chromosome 15 at bands 15q11.2-q12. The other common mechanism is complete loss of paternal chromosome 15, resulting in maternal
uniparental disomy (UPD), where both chromosome 15s are from the
mother.
Because the disease results
primarily from chromosomal
abnormalities, the recurrence risk for couples with one
affected child is
relatively low for a genetic disease, perhaps as low as 1 in 1000. Most cases are
sporadic, occurring without previous
family histories.