THE LONG QT SYNDROME - ION-CHANNEL DISEASES OF THE HEART

Once limited to discussions of the Jervell and Lange-Nielsen syndrome and Romano-Ward syndrome, the long QT syndrome (LQTS) is now understoo d to be a collection of genetically distinct arrhythmogenic cardiovasc ular disorders resulting from mutations in fundamental cardiac ion cha nnels that orchestrate the action potential of the human heart, Our un derstanding of this genetic ''channelopathy'' has increased dramatical ly from electrocardiographic depictions of marked QT interval prolonga tion and torsades de pointes and clinical descriptions of people exper iencing syncope and sudden death to molecular revelations in the 1990s of perturbed ion channel genes, More than 35 mutations in four cardia c ion channel genes--KVLQT1 (voltage-gated K-channel gene causing one of the autosomal dominant forms of LQTS) (LQT1), HERG (human ether-a-g o-go related gene) (LQT2), SCN5A (LQT3), and KCNE1 (mink, LQTS)--have been identified in LQTS, These genes encode ion channels responsible f or three of the fundamental ionic currents in the cardiac action poten tial, These exciting molecular breakthroughs have provided new opportu nities for translational research with investigations into genotype-ph enotype correlations and gene-targeted therapies.