Molecular determinants of left and right outflow tract obstruction

Congenital heart defects represent the most common group of human birth defects; they occur in 0.8-1% of live births and in 10% of spontaneously aborted fetuses. Heart defects seen in newborns typically represent specific morphogenetic defects of individual chambers or regions of the heart, with the remaining portions of the heart developing relatively normally. These developmental defects are commonly compatible with the intrauterine circulation, where the pulmonary circulation and systemic circulation work in concert, resulting in adequate embryonic growth and development. After delivery, however, significant cardiac symptoms develop. In many of these disorders, cyanosis is the earliest feature, while in others, cardiovascular collapse occurs before diagnosis. In this review, obstruction of the left and right sides of the heart are discussed. In these disorders, ventricular hypoplasia resulting in single ventricle physiologic characteristics is typical. The unaffected ventricle in these cases is usually morphologically and physiologically normal. These conditions include hypoplastic left heart syndrome and aortic coarctation on the left side, pulmonary stenosis, tetralogy of Fallot, and other complex right ventricle obstructive disorders. Many of these disorders occur in association with genetic syndromes identifiable by dysmorphic features. In some cases; the gene(s) has been identified or the genetic pathway has been defined. The purpose of this review is to discuss the molecular determinants of these obstructive disorders. Am. J, Med. Genet. (Semin. Med. Genet.) 97:297-303, 2000. (C) 2001 Wiley-Liss, Inc.