Heterotaxy is associated with CHD in 50% to 95% of cases, and includes cardiac findings such as atrioventricular canal defects that are frequently unbalanced. It is estimated to occur in 1 in 10,000 live births and constitutes approximately 3% of CHD cases. Heterotaxy has the highest relative risk among all classes of CHD, which supports a strong genetic component. Clinically relevant CNV have been identified in 15% to 26% of patients with heterotaxy syndrome. Autosomal dominant, autosomal recessive, and X-linked inheritance patterns have all been described, but unlike other types of CHD, de novo variants are not major contributors to heterotaxy. The hallmark of CHD in heterotaxy is that there is no absolutely defined pattern to the possible combinations of cardiac and vascular defects.
Hagen et al. 2016, Human Genetics 135(12), 1355–1364 / Pierpont et al. 2018, Circulation 138:e653–e711