Genetics of long QT syndrome

Methodist Debakey Cardiovasc J. Jan-Mar 2014;10(1):29-33. doi: 10.14797/mdcj-10-1-29.

Abstract

Long QT syndrome (LQTS) is a potentially life-threatening cardiac arrhythmia characterized by delayed myocardial repolarization that produces QT prolongation and increased risk for torsades des pointes (TdP)-triggered syncope, seizures, and sudden cardiac death (SCD) in an otherwise healthy young individual with a structurally normal heart. Currently, there are three major LQTS genes (KCNQ1, KCNH2, and SCN5A) that account for approximately 75% of the disorder. For the major LQTS genotypes, genotype-phenotype correlations have yielded gene-specific arrhythmogenic triggers, electrocardiogram (ECG) patterns, response to therapies, and intragenic and increasingly mutation-specific risk stratification. The 10 minor LQTS-susceptibility genes collectively account for less than 5% of LQTS cases. In addition, three atypical LQTS or multisystem syndromic disorders that have been associated with QT prolongation have been described, including ankyrin-B syndrome, Anderson-Tawil syndrome (ATS), and Timothy syndrome (TS). Genetic testing for LQTS is recommended in patients with either a strong clinical index of suspicion or persistent QT prolongation despite their asymptomatic state. However, genetic test results must be interpreted carefully.

Keywords: genetics; ion channel; long QT syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Mutational Analysis
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / genetics*
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Heart Rate / genetics*
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / physiopathology
  • Long QT Syndrome / therapy
  • Mutation*
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human

Grant support

Funding/Support: Intellectual property derived from Dr. Ackerman’s research program resulted in license agreements in 2004 between Mayo Medical Ventures and Genaissance Pharmaceuticals (now Transgenomic), leading to royalties for FAMILION-LQTS and FAMILION-CPVT genetic tests.