Perceived temporal trends in recognition and diagnosis of Prader-Willi syndrome served as the rationale for an updated epidemiological profile of individuals with this syndrome. Data from the Victorian Prader-Willi Syndrome Register were used to explore birth prevalence, birth characteristics, timing of diagnosis, and molecular mechanism, and to identify trends over time. Maternal age, birth gestation, small for gestational age, and sex were compared across molecular mechanisms. Between 1951 and 2012 there were 160 individuals with Prader-Willi syndrome, known to the Victorian Prader-Willi Syndrome Register, who were born in the Australian state of Victoria. The birth prevalence for individuals with a molecular diagnosis of Prader-Willi syndrome was estimated to be 1:15,830 for 2003-2012. Compared to 1973-1981, the decade 2003-2012 saw an increase in the rate of molecular diagnosis from 58% to 96%, more complete identification of the molecular mechanism (42% vs. 83%), earlier molecular diagnosis (1.3 years vs. 8.6 weeks), and a rise in the relative proportion of maternal uniparental disomy from 0% to 45%. One quarter of infants was born preterm and 53% were small for gestational age. This study confirms a temporal change in diagnostic patterns, suggests a greater relative contribution of maternal uniparental disomy as a molecular mechanism, provides a more robust estimate of birth prevalence and provides evidence of in utero growth restriction for this group. These findings have important clinical and health service delivery implications and pave the way for further research in Prader-Willi syndrome.

Background: Prader-Willi syndrome (MIM #176270; PWS) is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center. De novo balanced reciprocal translocations in 5 reported individuals had breakpoints clustering in SNRPN intron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and a de novo translocation t(4;15)(q27;q11.2).

Based on the findings, structured teaching about cerebral palsy is necessary within the medical curriculum at the University of Melbourne. Greater promotion of positive attitudes toward people with cerebral palsy and other disabilities is required.