Syndrome Synopsis: Prader-Willi Syndrome
by Beth A. Pletcher, MD, November 1999

Patients are usually referred for possible Prader-Willi syndrome (PWS) when an astute clinician sees a child with obesity and developmental delay. While the clinical features vary a great deal between individuals, there are some helpful clues that might assist in the identification of children with or without this condition. Furthermore, there are a number of other syndromes that have overlapping features with PWS.

Early in life many children with PWS have significant hypotonia and in some cases have feeding problems associated with failure to thrive during the first year of life. It usually isn't until 18 to 24 months of age that one may begin to see the voracious appetite and subsequent weight gain that one typically associates with this condition. Unlike other children with obesity where height tends to be equal to or greater than the 90th%ile when weight is above the 95th%ile, children with PWS often have heights at or below the 50th%ile despite significant weight gain. Also this height vs. weight discrepancy may become more pronounced over time.

Some features that might be seen more often in children with PWS include: bitemporal narrowing, almond-shaped eyes, lighter pigmentation than unaffected family members, small hands and feet, hypogonadism, cryptorchidism, and hypoplastic enamel leading to early, severe caries.

Diagnostic testing can be done as a two-pronged approach using both cytogenetic and molecular technologies. FISH cytogenetic studies looking for a submicroscopic deletion on chromosome 15 in the 15q11-13 region will pick up about 65% of children with PWS; molecular testing will detect an additional 30% of affected patients whose PWS is due to maternal uniparental disomy. For a more detailed laboratory discussion you may wish to refer to our website at http://www.genesatwork.org under Genetic Lab Testing Facts, subheading Molecular, Prader-Willi syndrome and Angelman syndrome.

Other syndromic causes of obesity and mental retardation include: Bardet-Biedl syndrome with additional features of polydactyly and retinitis pigmentosa as well as Cohen syndrome with down-slanting palpebrae, a prominent nose, and long, thin fingers and toes. Fragile X syndrome, although not typically associated with obesity, can have this as a prominent feature and may be missed if not considered in the differential diagnosis. Overgrowth syndromes such as Sotos syndrome would generally have a more proportionate overgrowth picture with macrocephaly and advanced bone age as well as a rather muscular build.