Hypoplastic left heart syndrome (HLHS) affects one of every 4,344 newborns. It has high morbidity and mortality but little is known about the pathogenesis.

In a recent paper published in the journal Pediatric Cardiology, Charles C. Hong, MD, PhD, and colleagues report that mutations in the gene NOTCH1 might be a cause.

Newborns with HLHS have a severely underdeveloped left ventricle and without treatment the condition is fatal. Treatment often includes cardiac transplant; therefore, discovering the cause could allow the creation of alternative treatments.

Using whole exome sequencing, Hong reported that a nonsense mutation in NOTCH1, which results in a severe truncated Notch1 transmembrane receptor, was the likely cause of HLHS and another heart condition – hypoplastic right heart syndrome – in one family.

Notch1 controls cell fate and has been implicated in various types of structural heart disease. The findings, which suggest that HLHS is caused by a defect in the aortic outflow tract rather than ventricular morphogenesis, could eventually lead to new treatments for the condition.