Abstract

Using a test based on parent of origin specific DNA methylation at the D15S63 (PW71) locus, we studied 385 patients (aged 1 to 36 years) for diagnostic confirmation of Prader-Willi syndrome (PWS) and 65 infants (aged 0 to 12 months) with severe hypotonia of unknown cause. Fifty eight of 385 patients were examined personally; 28/58 patients had PWS and lacked the paternal PW71 band and 30/58 patients, who did not have PWS, had a normal methylation pattern. In five of these patients, a differential diagnosis was made (Ohdo-like blepharophimosis syndrome, Alstrøm syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypoparathyroidism). A total of 327/385 blood samples was sent to us from outside. The test confirmed the diagnosis of PWS in 112/327 patients. Most of the other 215 patients lacked the major diagnostic criteria such as neonatal hypotonia, feeding problems, characteristic facies, and hypogenitalism. On the other hand, 29/65 hypotonic infants tested positive for PWS. We conclude that the PW71 methylation test detects most, if not all, patients with typical PWS and that PWS is often not recognised in infants and wrongly suspected in obese and mentally retarded patients.