Hypoplastic Left Heart Syndrome

Abstract

See related article, pages 1363–1370 Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart defects, accounting for 20% to 25% of mortality in infants born with congenital heart disease. In the United States, ≈2000 infants are born each year with HLHS.1 To date, there is a paucity of studies that define the underlying genetic, molecular and cellular mechanisms of HLHS.2–4 Most cases of HLHS are thought to arise secondarily because of decreased flow into the developing embryonic left ventricle, although in some cases, abnormal left ventricular growth could be the primary defect. There is strong evidence for a genetic etiology for HLHS, although very little is understood about the genetic mechanisms underlying HLHS. Nineteen percent of first degree relatives of infants with HLHS have a congenital heart defect.5 In addition, there are several chromosomal disorders that are associated with HLHS. For example, 10% of all infants born with a terminal 11q deletion (Jacobsen syndrome) have HLHS.6 Mutations in at least one gene, the cardiac transcription factor NKX2.5, have been identified in patients with HLHS.7,8 Similar to many of the most severe congenital heart defects, treatment strategies for HLHS have evolved and are still changing. The two current surgical strategies include the three-stage Norwood/Fontan procedure, or, alternatively, cardiac transplantation. The Norwood procedure, which is performed optimally in the neonatal period to avoid the development of pulmonary vascular disease, entails reconstructing the aortic arch, transecting the pulmonary artery, anastamosing the pulmonary artery root to the reconstructed aorta, and placing a systemic to pulmonary artery shunt (either from aorta or more recently, from the right ventricle). Although there has been significant progress in outcomes, neither surgical approach is curative and long-term outcomes are uncertain. Consequently, there has been an ongoing effort to develop …