Left Ventricular Noncompaction Cardiomyopathy in Children: A Focus on Genetic and Molecular Mechanisms

Left ventricular noncompaction (LVNC), also called noncompaction cardiomyopathy (NCM), is a myocardial disease that affects children and adults. Morphological features of LVNC include a noncompacted spongiform myocardium due to the presence of excessive trabeculations and deep recesses between prominent trabeculae. Incidence and prevalence rates of this disease remain contentious due to varying clinical phenotypes, ranging from an asymptomatic phenotype to fulminant heart failure, cardiac dysrhythmias, and sudden death. There is a strong genetic component associated with LVNC, and nearly half of pediatric LVNC patients harbor an identifiable genetic mutation. Recent studies have identified LVNC-associated mutations in genes involved in intercellular trafficking and cytoskeletal integrity, in addition to well-known mutations causing abnormal cardiac embryogenesis. Currently, the diagnosis is based on symptoms, as well as various diagnostic criteria, including echocardiography, electrocardiograms, and cardiac magnetic resonance imaging. Meanwhile, clinical management is primarily focused on the prevention of complications, such as heart failure, thromboembolic events, life-threatening arrhythmias, and stroke. Continued research is focusing on the genetic etiology, the development of gold-standard diagnostic criteria, and evidence-based treatment guidelines across all age groups. This review article will highlight the genotype-phenotype relationship within pediatric LVNC patients and assess the latest discoveries in genetic and molecular research aimed at improving their diagnostic and therapeutic management.