Epigenetic Abnormalities of 11p15.5 Region in Beckwith-Wiedemann Syndrome - A Report of Eight Indian Cases

Abstract

Objectives: To report a phenotypic series of eight patients of Beckwith-Wiedemann Syndrome (BWS) with abnormalities of 11p15.5 region to highlight the spectrum of phenotypic manifestations.

Methods: All the cases were evaluated using Methylation Specific Multiplex Ligation Dependent Probe Amplification (MS-MLPA) of 11p15.5 region to detect the abnormal methylation status of ICR1 (H19DR) and ICR2 (KvDMR) regions.

Results: The median age at diagnosis was 5.7 mo (range 1.5-13 mo) with female preponderance. Macroglossia, ear creases and abdominal wall defects were the major features. Hypomethylation at ICR2 and hypermethylation at ICR1 was observed in 6/8 and 2/8 patients respectively. No specific genotype and phenotype correlation was observed.

Conclusions: This report highlights the major clinical features of BWS that should prompt pediatricians to offer genetic testing to evaluate the epigenetic abnormalities using MS-MLPA, as it not only helps in appropriate counseling but also provides further guidance about the tumor risk surveillance.

Keywords: Beckwith-Wiedemann syndrome; Epigenetics; MS-MLPA; Overgrowth.