Genotype- and phenotype-guided approaches to the clinical management of congenital long QT syndrome have evolved from an improved understanding of the molecular underpinnings of the disease.
Understanding the molecular basis of congenital long QT syndrome enables genotype- and phenotype-guided approaches to diagnosis, risk stratification, and treatment.
Congenital long QT syndrome (LQTS) is a genetically heterogeneous group of heritable disorders of myocardial repolarization linked by the shared clinical phenotype of QT prolongation on electrocardiogram and an increased risk of potentially life-threatening cardiac arrhythmias. At the molecular level, mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore-forming α-subunits and accessory β-subunits central to the electromechanical function of the heart have been implicated in its pathogenesis. Over the past 2 decades, our evolving understanding of the electrophysiological mechanisms by which specific genetic substrates perturb the cardiac action potential has translated into vastly improved approaches to the diagnosis, risk stratification, and treatment of patients with LQTS. In this review, we describe how our understanding of the molecular underpinnings of LQTS has yielded numerous clinically meaningful genotype-phenotype correlations and how these insights have translated into genotype- and phenotype-guided approaches to the clinical management of LQTS.
Giudicessi et al. (2013) conducted a review in Congenital long QT syndrome (LQTS). Genotype- and phenotype-guided management was evaluated. Genotype- and phenotype-guided approaches to the clinical management of congenital long QT syndrome have evolved from an improved understanding of the molecular underpinnings of the disease.