Prader-Willi syndrome affects both sexes and all races and ethnicities equally, with the incidence of PWS occurring in approximately one in every 15,000-20,000 births. If Prader-Willi syndrome is suspected, genetic testing can confirm the diagnosis. A sample of blood will be drawn and sent to a specialized laboratory, and interpreted by a specialized physician called a geneticist.
Early diagnosis is critical for improving the prognosis. As soon as the diagnosis is made, therapeutic interventions such as occupational therapy, physical therapy, and speech and language therapy should begin, as well as medical interventions such as nutritional counseling and recombinant human growth hormone medication which can improve muscle tone, reduce developmental delays, improve short stature, and help manage excessive weight gain.
The mainstay for diagnosing PWS is a DNA Methylation Test which is the only test that will diagnose PWS caused by all three genetic mechanisms or subtypes: paternal deletion, maternal uniparental disomy (UPD), and imprinting center deletion. This test, also referred to as the “Prader-Willi/Angelman DNA methylation Panel”, detects more than 99% of affected individuals. DNA methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially in those who have atypical findings or are too young to show sufficient features to make the diagnosis on clinical grounds.
An oligo-SNP microarray will pick up the deletion class and size, as well as microdeletions that include the imprinting center and SNORD116, as well as 70% of uniparental disomy (UPD).
A FISH test (fluorescence in situ hybridization) will confirm a deletion on chromosome 15 if present, but will not reveal the size of the deletion nor the other two types of PWS, UPD or an imprinting center deletion, therefore it should not be used as the first genetic test.
If the DNA methylation test is positive, but the microarray or FISH test is normal, then the geneticist will need to do a DNA polymorphism analysis.
See GeneReviews for details of the PWS testing algorithm.