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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.