Additional Information

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with variable overgrowth features that may include neonatal hypoglycemia, hemihyperplasia, macroglossia, macrosomia, omphalocele, embryonal tumors (e.g., Wilms tumor and/or hepatoblastoma, among others), visceromegaly, renal abnormalities, and ear creases/pits. Alterations in DNA methylation across two distinct imprinting centers (ICs) located at 11p15 are associated with BWS. Approximately 10-20% of patients with BWS will have methylation alterations at both IC1 and IC2, likely secondary to paternal UPD of 11p15.5. Isolated hypermethylation of IC1, located upstream of the H19 gene, is found in about 5% of individuals with BWS. Isolated hypomethylation of IC2, located upstream of the LIT1 gene, is found in about 50% of individuals with BWS. Microdeletions and microduplications within the 11p15 region are also a cause of BWS (around 9% of patients), as are heterozygous maternal pathogenic variants in the CDKN1C gene (about 5% of patients). In approximately 20% of patients with clinical features of BWS, a molecular alteration cannot be identified.