Abstract

MOLECULAR ASPECTS OF LONG QT SYNDROME

Kamlesh Yadav*, K.S. Sodhi, Subhash Goyal, Rajesh Pandey, Jasbir Singh, Mukund Joshi

Abstract

Congenital long QT syndrome (LQTs) is a hereditary, heterogeneous group of cardiac diseases characterised by a prolongation of the QT interval. Disease prevalence is 1 in 2,500 live births. The two cardinal manifestations of LQTs are syncopal episodes and electrocardiographic abnormalities (including prolongation of the QT interval and T wave abnormalities) that may cause sudden cardiac arrest and death. At molecular level, mutations in 15 distinct LQTS susceptibility genes encoding ion channel pore forming α–subunits have been implicated in its pathogenesis. Mutations in genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1C, CAV3, SCN5A and SCN4B) cause the disease by prolonging the duration of the action potential. More than 70 drugs currently available in the market can cause drug-induced long QT syndrome (LQTS) which is associated with torsades de pointes arrhythmias, causing sudden cardiac death. These drugs block the human Ether-à-gogo Related Gene (hERG) channel involved in the repolarization phase of the cardiac action potential, and thus lengthen the QT interval. Treatment should always be started with β-blockers. Treatment of drug-induced LQTS includes identifying and withdrawing the culprit drugs(s), infusing magnesium and, in resistant cases, acceleration of the heart rate.

Keywords: Long QT syndrome, QT interval, genes, mutations, drugs.