Phenotypic discordance in monozygotic twins with a CDH2 variant

Monoallelic pathogenic variants consistent with Mendelian inheritance patterns causing congenital heart disease (CHD) have been increasingly identified as genetic testing, including genome sequencing (GS), has become more widely available within the clinical space. Here, we focus on a newly described pathogenic variant in CDH2 resulting in Agenesis of Corpus Callosum (ACC), Cardiac, Ocular, and Genital Syndrome (ACOGS). While previous studies document variable expressivity of the CDH2 variants in unrelated individuals, no cases have described such variable expressivity in twins with the same CDH2 variant. We present a novel case of likely monozygotic twins who both carried the same pathogenic CDH2 variant yet exhibited a spectrum of CHD with one presenting with hypoplastic left heart syndrome and the other with ventricular septal defect and pulmonary hypertension.