IllnessHypoplastic left heart syndrome, differential diagnosis

NGS +

Hypoplastic left heart syndrome (HLHS) comprises a heterogeneous group of congenital heart malformations characterized by the presence of a hypoplastic left ventricle with aortic and/or mitral hypoplasia or atresia. The term includes mitral atresia/aortic atresia or stenosis and/ or ventricular septal defects. The common feature of HLHS is a single functioning ventricle combined with some degree of hypoplasia of the ascending aorta. The physiological consequence is that the systemic blood flow is provided entirely or in part by the right ventricle via a ductus arteriosus. The latter and adequate mixing at the atrial level are therefore essential for postnatal survival. A restrictive or occluded foramen ovale can lead to pulmonary edema, hypoxia and terminal lung parenchymal disease. Genetic syndromes are present in 10-25% of patients with HLHS, including autosomal trisomies, Turner syndrome, Noonan, Holt-Oram, Jacobsen, Ellis-van Creveld, Potocki-Lupski and many other complex genetic syndromes as well as the CHARGE association. The inheritance appears complex, and a unified disease-associated chain of causation has not yet been identified. Therefore, in addition to molecular genetic testing, differential diagnosis primarily involves specialised clinical genetic characterization to rule out mild symptoms of a complex genetic syndrome, if any.

Reference: doi:10.1093/ejcts/ezaa188

• Allelic: Atrioventricular septal defect 3 (GJA1)
• Allelic: Conotruncal heart malformations, variable (NKX2-5)
• Allelic: Craniometaphyseal dysplasia, AR (GJA1)
• Allelic: Erythrokeratodermia variabilis et progressiva 3 (GJA1)
• Allelic: Hypothyroidism, congenital nongoitrous, 5 (NKX2-5)
• Allelic: Oculodentodigital dysplasia, AR (GJA1)
• Allelic: Palmoplantar keratoderma with congenital alopecia (GJA1)
• Allelic: Syndactyly, type III (GJA1)
• Allelic: Ventricular septal defect (NKX2-5)
• Atrial septal defect 7, with/-out AV conduction defects (NKX2-5)
• Hypoplastic left heart syndrome (HAND1)
• Hypoplastic left heart syndrome 1 (GJA1)
• Hypoplastic left heart syndrome 2 (NKX2-5)
• Hypoplastic left heart syndrome [panelapp red] (FOXL1)
• Oculodentodigital dysplasia (GJA1)
• Potocki-Lupski syndrome (RAI1 gene duplication)