Identification of Hypoplastic Left Heart Genotypes and Phenotypes; The Window toward Future Cell-Based Therapy: A Narrative Review.

Abstract

Hypoplastic left heart syndrome (HLHS) is a prevalent and lethal type of single ventricle anomaly. During early prenatal evaluations, left heart hypoplasia may be neglected due to its progressive features. It is a heterogeneous congenital heart disease with different phenotypes. Currently, there is no definite treatment for HLHS. This is in part due to its heterogeneous phenotypes that require different management. In addition, hindrances in recognizing the etiologic factors do not allow early preventive or therapeutic procedures. Phenotypic determination is fundamental to identifying the etiologic factors and therapeutic strategies. This review article introduces comprehensive information about different phenotypes and genotypes of HLHS and their novel molecular strategy. Genetic defects and flow-mediated mechanisms are the main known factors of HLHS. Recent studies reported additional data about its nonmendelian genetic origins associated with heterogeneous phenotypes. The genetic defects influence endocardium or cardiomyocyte development to yield early or late valve deformities and myocardial malformations. The new molecular therapeutic methods are essentially based on genetic etiologies. The principal therapeutic purpose is reinforcing the function of the right ventricle in patients with nonfunctional left ventricles. The ultimate desire is to create a biventricular heart in selected cases.