Beckwith-Wiedemann syndrome

The Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth syndrome with a variable clinical appearance. The phenotype normalizes with age but the diagnosis of BWS is important as syndrome-specific complications may develop, in particular as a result of a 400-fold increased risk of patients developing certain tumor entities, predominantly nephroblastomas (Wilms' tumors) and hepatoblastomas, within the first years of life. BWS displays a clinical overlap with other syndromes so that an unambiguous molecular diagnostic is required for risk assessment and appropriate therapy. At the molecular level BWS is associated with the chromosomal region 11p15.5, where two clusters with imprinted genes are located. In patients both genetic mutations and in most cases aberrant DNA methylation can be observed, which pathogenically affect the gene dosage of functionally available monoallelically expressed 11p15.5 genes. Currently only a very incomplete genotype-phenotype correlation exists for BWS. Current research projects provide insights in the molecular etiopathogenesis of the syndrome by identifying interacting partners which modify the epigenetic regulation of imprinted 11p15.5-genes.