Hypoplastic left heart syndrome results from defective development of the aorta proximal to the entrance of the ductus arteriosus and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus ... Hypoplastic left heart syndrome results from defective development of the aorta proximal to the entrance of the ductus arteriosus and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged (Brekke, 1953). - Genetic Heterogeneity of Hypoplastic Left Heart Syndrome Hypoplastic left heart syndrome-2 (HLHS2; 614435) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q35.1. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with HLHS.
Brekke (1953) described 2 brothers, born 2 years apart, who died in the neonatal period. On autopsy, the boys had atresia or hypoplasia of the aortic orifice and hypoplasia of the left ventricle and ascending aorta, patency of ... Brekke (1953) described 2 brothers, born 2 years apart, who died in the neonatal period. On autopsy, the boys had atresia or hypoplasia of the aortic orifice and hypoplasia of the left ventricle and ascending aorta, patency of the foramen ovale and of the ductus arteriosus, and hypertrophy of the right ventricle and right atrium. A previous pregnancy had resulted in a fullterm stillborn infant in which an autopsy was not performed. Kojima et al. (1969) described hypoplastic left heart syndrome in sibs. Shokeir (1971) described 13 patients in 5 families. Parental consanguinity was present in 3 sibships. In all affected infants, the course of the disease was inexorably progressive and ultimately fatal. Loffredo et al. (2004) ascertained families of 38 probands with hypoplastic left heart, 46 with coarctation of the aorta (120000), and 22 with d-transposition of the aorta (DTGA; 608808), with the latter group serving as 'disease controls.' Cardiovascular malformations were detected more frequently in first-degree relatives of probands with hypoplastic left heart (19.3%) or coarctation of the aorta (9.4%) than among DTGA families (2.7%). Less than 1% of second-degree relatives were affected in all 3 groups. In third-degree relatives, cardiovascular malformations were detected in 1.8% of families with hypoplastic left heart compared to 1.2% in families with coarctation of the aorta and 0.4% in families with DTGA. The predominant types of malformation seen in relatives were left-sided obstructive lesions. Loffredo et al. (2004) stated that this confirmed the familial aggregation of congenital heart defects among infants with hypoplastic left heart and coarctation of the aorta. The spectrum of left ventricular outflow tract obstruction (LVOTO) consists of hypoplastic left heart or left ventricle, aortic valve stenosis and bicuspid aortic valve (109730), hypoplastic aortic arch, and coarctation of the aorta (120000). Wessels et al. (2005) described 4 families with presumed autosomal dominant inheritance of LVOTO. In these families, LVOTO showed a wide clinical spectrum, with some members having severe anomalies such as hypoplastic left heart and others having only minor anomalies such as mild aortic valve stenosis. Wessels et al. (2005) concluded that their findings supported the suggestion that all anomalies of the LVOTO spectrum are developmentally related and sometimes can be caused by a single gene defect.
In 8 pediatric heart transplant recipients with hypoplastic left heart syndrome, Dasgupta et al. (2001) identified 4 substitutions in the GJA1 gene: 2 missense mutations and 2 silent polymorphisms (see 121014.0011).