Clues or Miscues?

Abstract

The congenital long-QT syndrome (LQTS) is an inherited condition associated with a prolongation of the QT interval on the ECG characterized by syncope, seizures, and sudden death secondary to ventricular arrhythmia, specifically torsade de pointes.1 LQTS is particularly notable because it affects seemingly healthy children and young adults, often with no apparent serious health issues. Unfortunately, LQTS may present dramatically with sudden cardiac death in 10% of children and syncope or seizures in 30% to 40% as the first symptom.2 Importantly, although LQTS has a high mortality when not diagnosed and treated, the currently available therapies are very effective in preventing sudden cardiac death.3 Thus, making the correct diagnosis in as many individuals with LQTS as possible before life-threatening symptoms emerge is critical. Article p 2613 The condition now designated as LQTS was first described as the Jervell Lange-Nielson syndrome (LQTS with hearing deficit) in 1957.4 A few years later, the Romano Ward syndrome was described (LQTS with normal hearing).5,6 In 1979, the International LQTS Registry was established. Much of the information about LQTS, correlations between genotype and phenotype, risk stratification, and treatment of LQTS stems from information gleaned from this registry and other large cohorts.7–11 Identification of the gene mutations in cardiac ion channels in the 1990s led to further understanding of LQTS. At least 9 genes have been identified that encode for proteins that modulate ion channel structure, function, and signaling or trafficking; alter cardiac repolarization; and increase the risk for ventricular arrhythmias.3,12 The identified genes are thought to represent 70% of the mutations that cause LQTS, with others yet to be identified or their location on identified genes yet to be found. The authors13 of “Diagnostic Miscues in Congenital Long-QT Syndrome” in this issue of Circulation have illustrated many …