The long QT syndromes

Abstract

The congenital long QT syndromes are a heterogeneous group of disorders that are characterized by prolongation of the QT interval on the 12-lead electrocardiogram, episodes of syncope, ventricular arrhythmias such as torsades de pointes and a high incidence of sudden death. The autosomal dominant form of congenital QT prolongation, the Romano-Ward long QT syndrome, is the most common of these disorders and has been demonstrated by linkage analysis studies to exhibit extensive genetic heterogeneity. These studies have determined that at least five different genes can cause the long QT syndrome. Positional cloning studies have led to the discovery of three genes which together appear to be responsible for nearly 90% of the autosomal dominant cases of congenital long QT syndrome. Further functional characterization of these three genes, the KVLQT1 potassium channel, the HERG potassium channel and the SCN5A voltage-gated cardiac sodium channel, as well as the identification and characterization of the other long QT syndrome genes, may allow improved diagnosis and therapy for these disorders. Furthermore, the increased understanding of myocardial repolarization that is gained from characterization of these genes may lead to improved treatment for other ventricular arrhythmias, including those related to drug-induced potassium channel blockade, central nervous system insult, and, possibly, myocardial infarction.