SEARCH

SEARCH BY CITATION

Keywords:

  • overgrowth;
  • genomic imprinting;
  • embryonal tumors;
  • chromosome 11p15;
  • imprinted domains;
  • epigenotype;
  • monozygotic twinning

Abstract

Beckwith–Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome associated with an increased risk for embryonal tumor development. BWS provides an ideal model system to study epigenetic mechanisms. This condition is caused by a variety of genetic or epigenetic alterations within two domains of imprinted growth regulatory genes on human chromosome 11p15. Molecular studies of BWS have provided important data with respect to epigenotype/genotype–phenotype correlations; for example, alterations of Domain 1 are associated with the highest risk for tumor development, specifically Wilms' tumor. Further, the elucidation of the molecular basis for monozygotic twinning in BWS defined a critical period for imprint maintenance during pre-implantation embryonic development. In the future, such molecular studies in BWS will permit enhanced medical management and targeted genetic counseling. © 2005 Wiley-Liss, Inc.