CSM Ng, CWM Au, HM Luk

Abstract

Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterised by overgrowth and an increased risk of embryonal tumours. Here, we present two local pairs of monozygotic twins with BWS. In both cases, one twin exhibited more severe features while the other twin had milder or no manifestations of the syndrome. Genetic analysis revealed concordant loss of methylation at the ICR2 region of chromosome 11p15 in both peripheral blood and buccal samples of the affected twins. Yet the unaffected twins showed loss of methylation only in peripheral blood, suggesting tissue-specific mosaicism of epigenetically aberrant cells. These cases emphasise the variable expressivity of BWS within monozygotic twin pairs and highlight the caveat of using peripheral blood alone for diagnosis. Further research is necessary to elucidate the underlying mechanisms contributing to this phenotypic variability, and long term data is needed to establish whether tumour surveillance is needed for the clinically unaffected ones in particular.