Congenital Long QT Syndrome: A Review of Genetic and Pathophysiologic Etiologies, Phenotypic Subtypes, and Clinical Management.

ABSTRACT

Congenital Long QT Syndrome (CLQTS) is the most common inherited arrhythmia. The QT interval, which marks the duration of ventricular depolarization and repolarization in the myocardium, can be prolonged due to mutations in genes coding for the ion channel proteins that govern the cardiac action potential. The lengthening of the QT interval can lead to a wide range of clinical symptoms, including seizures, torsades de pointes, and fatal arrhythmias. There is a growing body of evidence that has revealed the genetic mutations responsible for the pathophysiology of CLQTS, and this has led to hypotheses regarding unique triggers and clinical features associated with specific gene mutations. Epidemiologic evidence has revealed a 1-year mortality rate of approximately 20% in untreated CLQTS patients, and a <1% of 1-year mortality rate in treated patients, underscoring the importance of timely diagnosis and effective clinical management. There are many phenotypic syndromes that constitute CLQTS, including but not limited to, Jervell and Lange-Nielsen syndrome, Romano and Ward syndrome, Andersen-Tawil syndrome, and Timothy syndrome. In this review, we aim to (1) summarize the genetic, epidemiologic, and pathophysiological basis of CLQTS and (2) outline the unique features of the phenotypic subtypes and their clinical management.