Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is characterized by severe muscle weakness, feeding difficulties and failure to thrive in early infancy, followed in later infancy by uncontrolled appetite and severe obesity. All patients have some degree of intellectual disability and behavior problems are common. In addition, PWS patients show short stature, small hands and feet and undescended testes in males.

There are a number of genetic changes that cause PWS, although each produces a similar clinical phenotype. Approximately 70-75 per cent of PWS cases are the result of a deletion of the paternal copy of the PWS critical region on chromosome 15. Approximately 25 per cent of cases have received two copies of chromosome 15 from their mother and none from their father, maternal uniparental disomy (matUPD). Like the deletion patients, the UPD patients are deficient for paternally derived genes in the PWS critical region. Approximately five per cent of patients have an ‘imprinting mutation’ which alters the normal expression of paternal genes in the PWS critical region.

DNA in the PWS critical region is methylated. If the normal expression of genes in the critical region is altered due to deletion, UPD or imprinting mutations, the methylation pattern is also changed. Therefore, testing the methylation status of genes within the critical region allows these genetic alterations to be detected. For molecular analysis, the methylation status of the gene SNRPN within the PWS critical region is measured. Abnormal methylation of the paternally derived genes is diagnostic of Prader-Willi syndrome. Point mutations or genetic rearrangement in the critical region, although very rare, may also result in PWS despite normally methylated paternal and maternal genetic contributions. These mutations are not detected by methodology currently in place in the Genome Diagnostics Laboratory.

See related information sheet: Prader-Willi syndrome