The genetic basis of long QT and short QT syndromes: a mutation update

Hum Mutat. 2009 Nov;30(11):1486-511. doi: 10.1002/humu.21106.


Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization abnormalities that are characterized by length perturbations of the QT interval as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity for ventricular tachycardia of the torsades de pointes (TdP) type are characteristic of LQTS, while SQTS is characterized by shortened QT interval with tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes represent a high risk for syncope and sudden death. LQTS exists as a congenital genetic disease (cLQTS) with more than 700 mutations described in 12 genes (LQT1-12), but can also be acquired (aLQTS). The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions. The latter includes Jervell and Lange-Nielsen syndrome (JLNS), Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further complicated by the occurrence of double and triple heterozygotes in LQTS and a considerable number of nonpathogenic rare polymorphisms in the involved genes. SQTS is a very rare condition, caused by mutations in five genes (SQTS1-5). The present mutation update is a comprehensive description of all known LQTS- and SQTS-associated mutations.

Publication types

  • Review

MeSH terms

  • A Kinase Anchor Proteins / chemistry
  • A Kinase Anchor Proteins / genetics
  • Ankyrins / chemistry
  • Ankyrins / genetics
  • Arrhythmias, Cardiac / genetics
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Caveolin 3 / chemistry
  • Caveolin 3 / genetics
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Genotype
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Long QT Syndrome / genetics*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Mutation*
  • Syndrome


  • A Kinase Anchor Proteins
  • AKAP9 protein, human
  • ANK2 protein, human
  • Ankyrins
  • CAV3 protein, human
  • Calcium-Binding Proteins
  • Caveolin 3
  • Cytoskeletal Proteins
  • Ion Channels
  • Membrane Proteins
  • Muscle Proteins
  • syntrophin alpha1