Congenital long QT syndrome: The value of genetics in assessing the prognosis

The congenital long QT syndrome (QTL) is a heterogenic clinical and genetic entity characterised by prolongation, of the QT interval which may be comp licated by syncope and sudden death. Four genes have been identified for th e cardiac potassium (KCNQ1, HERG and KCNE1) and sodium (SCN5A). The aim of this study was to assess the prognosis of the disease by the sit e of mutation identified on the morbid gene. Thirty-two genotyped families participated to this study. Each subject gave a clinical history, an ECG an d a search for genetic mutation. Eighteen mutations in the transmembrane do mains of KCNQ1 were identified in 25 families and 2 mutations in the C-term inal part were found in 4 families. The phenotype was less severe in C-terminal part mutations : less syncopes and sudden deaths (22 vs S5%, p < 0.001) and a shorter QTc (458 +/- 31 ms v s 479 +/- 31 ms, p = 0.0003). Three mutations were detected in the C-termin al part of HERG in 3 different families. Their phenotype was less severe wi th syncoped related to hypokalemia. The authors also report the case of a f amily in which two subjects who were the most severely affected had two mut ations, one in HERG and the other in KCNQ1. This study confirms the value of a genetic research in assessing the severi ty of the congenital long QT syndrome.