The European Prader-Willi Syndrome Clinical Research Database: an aid in the investigation of a rare genetically determined neurodevelopmental disorder.

BACKGROUND: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research database has been established to structure data collection and to enable multinational investigations into the development of children and adults with PWS. METHODS: As part of a joint basic science and clinical study of PWS funded through Framework 6 of the European Union (EU), an expert multidisciplinary group was established that included clinicians involved in PWS research and clinical practice, expert database software developers, and representatives from two national PWS Associations. This group identified the key issues that required resolution and the data fields necessary for a comprehensive database to support PWS research. RESULTS: The database consists of six 'index' entry points and branching panels and sub-panels and over 1200 data 'fields'. It is Internet-based and designed to support multi-site clinical research in PWS. An algorithm ensures that participant data are anonymous. Access to data is controlled in a manner that is compatible with EU and national laws. The database determines the assessments to be used to collect data thereby enabling the combining of data from different groups under specifically agreed conditions. The data collected at any one time will be determined by individual research groups, who retain control of the data. Over time the database will accumulate data on participants with PWS that will support future research by avoiding the need for repeat data collection of fixed data and it will also enable longitudinal studies and treatment trials. CONCLUSION: The development of the database has proved to be complex with various administrative and ethical issues to be addressed. At an early stage, it was important to clarify the exact function of the database. It was agreed that it was primarily to support grant-funded research rather than clinical practice. The most complex issues that had to be addressed were concerned with data ownership and establishing the rules for data entry, retrieval and sharing that are compatible with data protection laws, and which are likely to be acceptable to participants and their families and to individual research groups.

Cross-cultural comparisons of obesity and growth in Prader-Willi syndrome.

Introduction The present study reports cross-cultural comparisons of body mass index (BMI) and growth in Prader-Willi syndrome, a neurodevelopmental disorder associated with obesity, growth restriction and mild learning disability. Our objectives were to: (1) compare rates of obesity in adults with Prader-Willi syndrome (PWS) in France, with data available from Belgium, the UK and the USA; (2) compare growth of French children with PWS with their counterparts in Germany and the USA; and (3) evaluate the contribution of genetic, medical and social parameters to obesity outcome in French children and adults with PWS. Method (1) Cross-sectional comparison of BMI of 40 French adults, 38 Belgian adults, 46 British adults and 292 North American adults; (2) Construction of growth curves for French children aged 2-20 years from longitudinal data for 150 individuals with PWS, and comparison with published growth curves from Germany and the USA; and (3) Longitudinal regression analysis of 141 French children and adults to determine the factors contributing to obesity outcome. Results A total of 82.5% French adults with PWS have BMI > 30 compared with 65.8% in Belgium (n.s.), 58.2% in the USA (P < 0.005), and 54.3% in the UK (P < 0.01). Higher rates of obesity in females vs. males were found in the USA sample (P < 0.001) but not in the other samples. In contrast to adults, growth curves for French children with PWS show similar rates of growth compared with children with PWS in Germany and the USA. The principal determining factors of BMI status in the French PWS population are age (P < 0.0001), cohort (born within the last 15 years vs. born over 15 years ago, P < 0.0002) and growth hormone replacement therapy (P < 0.0002). Significant subsidiary effects include domestic situation (P < 0.0001), genetic diagnosis (P < 0.0001) and age of diagnosis (P < 0.0001). Conclusions French adults with PWS have significantly higher rates of obesity than adults in the UK and the USA, but growth in French children with PWS is similar to the USA and Germany. Clinical management has a greater impact on obesity outcome in PWS than cultural factors.