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Genetics of Adult and Fetal Forms of Long QT Syndrome

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Genetic Causes of Cardiac Disease

Part of the book series: Cardiac and Vascular Biology ((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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Authors and Affiliations

  1. Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy

    Lia Crotti, Alice Ghidoni & Federica Dagradi

  2. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

    Lia Crotti

  3. Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy

    Lia Crotti

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  1. Lia Crotti
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  2. Alice Ghidoni
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  1. IIEG, University of Lubeck, LĂĽbeck, Germany

    Jeanette Erdmann

  2. I Medical Dept (Cardiology), Klinikum Rechts der Isar of the Technical University Munich, MĂĽnchen, Bayern, Germany

    Alessandra Moretti

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Crotti, L., Ghidoni, A., Dagradi, F. (2019). Genetics of Adult and Fetal Forms of Long QT Syndrome. In: Erdmann, J., Moretti, A. (eds) Genetic Causes of Cardiac Disease. Cardiac and Vascular Biology, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-030-27371-2_1

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