Neonates with HLHS do not typically have a heart murmur, but in some cases, a pulmonary flow murmur or tricuspid regurgitation murmur may be audible.Co-occurring tricuspid regurgitation or right ventricular dysfunction can cause hepatomegaly to develop. Pathogenesis
The majority of HLHS cases are sporadic meaning they arise in patients with no family history of HLHS. Some cases may have a genetic component, as HLHS has been shown to be heritable and associated with specific gene mutations. Possible contributing factors may include intrauterine infarction, infectious changes, and a selective left ventricular cardiomyopathy. Genetics
Genetic loci associated with HLHS include GJA1 (connexin 43), HAND1, NKX2.5, 10q22, and 6q23. There is a slight risk of recurrence in future pregnancies, estimated to be 2-4%, which increases to 25% in families with two affected children. This is thought to be mediated by genetic mutations with incomplete penetrance.HLHS is also associated with several genetic syndromes, including trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), partial trisomy 9, Turners syndrome (XO), Jacobsen syndrome (11q deletion syndrome), Holt-Oram syndrome, and Smith-Lemli-Opitz syndrome. Altered Blood Flow
A popular theory termed the "no flow, no grow" hypothesis suggest that primary anatomic defects of the aortic and mitral valves lead to malformations of the left ventricle and its outflow tract. These primary defects can be divided into those that lead to outflow tract obstruction or reduced left ventricular filling. Outflow tract obstruction leads to left ventricular hypertrophy and reduction in the left ventricular lumen. One example of this would be in the case of aortic stenosis.
The right ventricle performs the traditional job of the left, supplying the body with oxygenated blood, while the passive systemic venous pressure performs the traditional job of the right, passing deoxygenated blood to the lungs. Fetal surgery
Interventions performed during fetal development are under investigation. In fetuses with hypoplastic left ventricles and an intact interatrial septum, percutaneous atrial septostomy has been attempted. Prognosis
95% of untreated infants with HLHS die in the first weeks of life.Early survival has improved since the introduction of the Norwood procedure. Since there are no long-term studies of HLHS adults, statistics are usually derived from post-Fontan patients; it is estimated that 70% of HLHS patients may reach adulthood.Prognosis is dependent upon the health of the child, as there is an increased demand on respiratory and heart rate in infants during common childhood illnesses. This fragile population has little cardiac reserve to accommodate these demands and provide hemodynamic stability during illnesses.Children with HLHS and other comparable single-ventricle conditions, as a group, have poorer neurodevelopmental outcomes than their healthy peers. Deficits in language, executive functioning, and higher rates of anxiety and depression disorders have been demonstrated. Some of these outcomes may be a consequence of genetic factors associated with HLHS, and others may be modifiable through changes to procedures and to the healthcare environment. There is an emerging clinical consensus around the importance of continuous neurodevelopmental surveillance from the earliest years into adulthood.