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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Paula L Hedley
  • Poul Jørgensen
  • Sarah Schlamowitz
  • Romilda Wangari
  • Johanna Moolman-Smook
  • Paul A Brink
  • Kanters, Jørgen K.
  • Valerie A Corfield
  • Michael Christiansen
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.
Original languageEnglish
JournalHuman Mutation
Volume30
Issue number11
Pages (from-to)1486-511
Number of pages25
ISSN1059-7794
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: A Kinase Anchor Proteins; Ankyrins; Arrhythmias, Cardiac; Calcium-Binding Proteins; Caveolin 3; Cytoskeletal Proteins; Genotype; Humans; Ion Channels; Long QT Syndrome; Membrane Proteins; Muscle Proteins; Mutation; Syndrome

ID: 18763845