Prevalence of beckwith-wiedemann syndrome in North West of Italy

Although Beckwith-Wiedemann syndrome (BWS, OMIM #130650) is the most common genetic overgrowth disorder, data on its epidemiology are scanty and the estimates of its occurrence show wide variability. The aim of this study is to assess its prevalence in Piedmont Region (Italy). We included in the study all patients diagnosed with BWS born in Piedmont from 1997 to 2009 through a search in the Italian Registry for Rare Diseases. This source was further validated with data from the network of Regional Clinical Genetics services and surveys in extra-regional Clinical Genetics centres, laboratories and the Italian BWS patients association. All cases were further ascertained through physical exam, medical history and specific molecular tests. The search identified 46 clear-cut cases of BWS born across the 13-year period, providing a prevalence of 1:10 340 live births (95% confidence interval 1:7,752-13,698 live births). Among the 41 patients who underwent molecular tests, 70.7% were positive, showing hypomethylation of the IC2 imprinting center (29.3%), paternal chromosome 11 uniparental disomy (pUPD11, 24.4%), IC1 hypermethylation (14.6%), CDKN1c mutation (2.4%), whereas 29.3% had negative molecular tests. The study provides an approximate BWS prevalence of 1:10,000 live birth, the highest reported to date.