Hypoplastic Left Heart Syndrome

Abstract

Hypoplastic left heart syndrome (HLHS) is the most common severe congenital heart defect comprising 1-2% of all congenital heart defects and 7-9% of all anomalies diagnosed within the first year of life. It is also the most common congenital cardiac malformation involving a single ventricle. It is encountered more frequently in males than in females, with a 67% male predominance. It is a uniformly fatal condition without surgical intervention, and 95% of these infants will have died within the first month of life. In most children with HLHS, the cause of this severe malformation is not known, and multifactorial mode of inheritance is likely for most cases (Freedom RM, Black MD, Benson LN, Moss and Adams Heart Disease in Infants, Children, and Adolescents. Lippincott Williams and Wilkins 1011-1025, 2001). It typically occurs sporadically in otherwise normal infants. In some children, HLHS is known to be genetically determined. These cases may be due to mutations in the GJA1 gene on chromosome 6q22 with autosomal recessive inheritance (HLHS1) or the NKX2-5 gene on chromosome 5q35.1 with autosomal dominant inheritance (HLHS2). Somatic mutations in the HAND1 gene have been identified in tissue samples from patients with HLHS [2, 3]. HLHS has also been reported in association with certain genetic disorders including Turner syndrome, Jacobsen syndrome, trisomy 13, and trisomy 18 (Martinez Crespo et al. Ultrasound Obstet Gynecol 21:490- 493, 2003; Ye et al. Hum Mol Genet 19:648-656, 2010; Reis et al. Obstet Gynecol 93(4):532-535, 1999).