RECENT ADVANCES IN UNDERSTANDING THE MOLECULAR MECHANISMS OF THE LONGQT SYNDROME

Competing theories to explain the congenital long QT syndrome have inc luded an imbalance in sympathetic innervation of the heart or a defect in repolarizing ion currents, Recent studies have identified at least four chromosomal loci at which mutations cause the congenital long QT syndrome in different families, The specific genes mutated in affecte d individuals have been identified at two of these loci, and both enco de cardiac ion channels, The affected genes are SCN5A, the cardiac sod ium channel gene, and HERG, whose protein product likely underlies I-K r, the rapidly activating delayed rectifier, Thus, currently available evidence indicates that the congenital long QT syndrome is a primary disease of cardiac ion channels, Abnormalities in either inward or out ward currents can cause the disease, Ongoing studies are evaluating th e function of the mutant ion channels and the relationship between ind ividual mutations and the clinical manifestations of the syndrome.