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Genetics of Adult and Fetal Forms of Long QT Syndrome

  • Lia Crotti
  • Alice Ghidoni
  • Federica Dagradi
Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 7)

Abstract

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by prolongation of QT interval at surface ECG, T-wave abnormalities, and high risk of life-threatening arrhythmias in otherwise healthy young individuals. Currently the LQTS diagnosis is genetically confirmed in nearly 75–85% of LQTS patients, revealing a good knowledge of the genetic bases of the disease. The main LQTS genes are KCNQ1, KCNH2, and SCN5A encoding potassium and sodium cardiac ion channels responsible of the cardiac action potential duration. Minor contributors of LQTS genetic background include genes encoding other cardiac ion channels, ancillary subunits, and protein components forming channels’ macromolecular complexes.

Fetal and neonatal forms of LQTS are the most aggressive form of the disease, frequently associated with typical ECG features as very prolonged QTc, 2:1 functional atrioventricular block, T-wave alternans, and life-threatening arrhythmias. The genetic basis of these early-onset cases is peculiar. Indeed, while potassium channel mutations are the most commonly observed causes of adult LQTS, fetal and neonatal forms of the disease are mainly due to aggressive sodium channel mutations or to mutations affecting calcium channel activity, as in Timothy syndrome, triadin knockout syndrome, and calmodulin-LQTS. Aggressive forms of LQTS can also cause sudden infant death syndrome (SIDS) or intrauterine fetal death.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Lia Crotti
    • 1
    • 2
    • 3
  • Alice Ghidoni
    • 1
  • Federica Dagradi
    • 1
  1. 1.Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Center for Cardiac Arrhythmias of Genetic OriginMilanItaly
  2. 2.Department of Medicine and SurgeryUniversity of Milano-BicoccaMilanItaly
  3. 3.Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic SciencesSan Luca HospitalMilanItaly

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