Most Beckwith-Wiedemann syndrome (BWS) cases are sporadic; nonetheless, imprinting center 1 (IC1) microdeletions have been suggested as a rare cause of familial BWS, with ~ 20 reported cases. We report 13 cases from nine families with IC1 microdeletions. Recurrent 1.4-kb, 1.8-kb, and 2.2-kb deletions were observed. IC1 hypermethylation was identified in all families, and we established a statistically significant relationship between IC1 microdeletions and hypermethylation (OR: 108.17, p = 2.76e-13). This study confirms IC1 microdeletions as a cause of familial BWS, expands the understanding of their molecular mechanisms, and supports a Likely Pathogenic clinical classification for IC1 microdeletions.
Keywords: BWS; Beckwith–Wiedemann syndrome; Familial BWS; IC1 hypermethylation; IC1 microdeletion; Imprinting center 1; Imprinting disorder; MS-MLPA.
© 2025. The Author(s).