Prader-Willi syndrome is associated with neonatal hypotonia and feeding difficulties, changing to excessive eating later in infancy and childhood. Motor, cognitive, and language development are typically delayed. Prader-Willi syndrome is caused by the absence of the paternally-inherited criticial region of chromosome 15.

For diagnosis, DNA methylation study of the PWS/AS Critical Region is the recommended method. If the methylation pattern is characteristic of maternal inheritance, this is diagnostic for Prader-Willi syndrome. Maternal inheritance of the PWS/AS critical region can be caused by deletions of the paternal allele, receiving two copies of chromosome 15 from the mother (uniparental disomy) or defects in the imprinting process.

If the methylation test is positive, a FISH (fluorescence in situ hybridization) test can be used to distinguish between uniparental disomy and a deletion.

99% of cases of Prader-Willi syndrome will be diagnosed by DNA methylation studies.