WBS is an overgrowth malformation syndrome characterized by highly variable expressivity, associated with predisposition to different types of pediatric tumors including Wilms' tumor (WT), adrenocortical carcinoma (ADCC), rhabdomyosarcoma (RMS) and hepatoblastoma (HEP). Most cases are sporadic, however 15% of the cases are familial. Cytogenetic, genetic and molecular analysis of the different forms of this syndrome and associated tumors have provided increasing evidence that the gene (or genes) map to 11p15.5 and that genomic imprinting can account for the strange genetics of this syndrome/tumors [1]. Two candidate genes, H19 and Igf2, which are both imprinted, but in opposite direction, map close to but not within one of the two smallest region(s) defined both by constitutional and tumoral rearrangements. These two genes, H19 and Igf2, and their specific parental imprint, may thus account for the pattern of inheritance observed, the variable expressivity, the specific loss of alleles and the loss of imprint. However, that these genes map 400 kb away from one cluster of breakpoints observed in the cytogenetic cases of WBS suggests that other genes could be involved. Indeed, although mapping to a different subregion, a sequence wit the properties of a tumor Suppressor (rhabdomyosarcoma cell line) has recently been isolated [2].

Furthermore, neither reduplication of the active Igf2 paternal allele nor relaxation of Igf2 imprinting is sufficient for tumorigenesis, thus indicating that other mutation(s) must occur. The phenotypic consequences of these aberrant expressions will be better understood when the tissues, the stage of development or the state of differentiation are precisely identified [3-5].