Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia and failure to thrive, early childhood-onset hyperphagia with resulting obesity, short stature, small hands and feet, hypogonadotropic hypogonadism and mental retardation. The majority of patients (70%) have interstitial deletions of the paternal chromosome 15 (q11.2-q13). Approximately 26% have maternal uniparental disomy (UPD), 2% have chromosome 15 translocations, and 2% have mutations of the imprint control region.

The American College of Medical Genetics has described two approaches to laboratory diagnosis. The first approach, to be used in cases with a high degree of suspicion of PWS, is DNA methylation analysis which will detect PWS cases caused by deletion, UPD or imprint defects. If the results are negative, chromosome analysis should be performed to rule out chromosome abnormalities. In the second approach, chromosome analysis and FISH are carried out first to detect PWS patients with deletions or translocations and non-PWS patients with chromosome abnormalities. If negative, DNA methylation studies can be performed to detect PWS cases with UPD and imprint control mutations.

For Testing Methodology, Specimen Requirements and CPT codes, refer to:

Prader-Willi Syndrome: DNA Methylation Testing

Prader-Willi Syndrome: Uniparental Disomy Analysis

Prader-Willi Syndrome: FISH Analysis