Human genetics of Ebstein anomaly

Abstract

Ebstein anomaly is a congenital malformation of the tricuspid valve characterized by abnormal attachment of the valve leaflets, resulting in varying degrees of valve dysfunction. The anatomic hallmarks of this entity are the downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve, and additional intracardiac malformations are common. Familial recurrence and an association with structural genomic variation, including syndromic forms, point to a strong genetic influence in pathogenesis. Gene content of more commonly observed chromosomal imbalances suggests that multiple cardiac regulators can contribute to Ebstein anomaly. A specific association has emerged with the definition of left ventricular noncompaction and Ebstein anomaly, caused by autosomal dominant mutations in the beta-myosin heavy chain MYH7. The current gene catalogue discussed here suggests that diverse developmental pathways are affected in Ebstein anomaly and that variable expressivity and incomplete penetrance are commonly observed phenomena.