TY - JOUR
T1 - Genotype- and Phenotype-Guided Management of Congenital Long QT Syndrome
AU - Giudicessi, John R.
AU - Ackerman, Michael J.
N1 - Funding Information:
Funding Sources: This work was supported by the Windland Smith Rice Sudden Comprehensive Sudden Cardiac Death Program (to M.J.A.). J.R.G. is supported by a National Heart Lung and Blood Institute Ruth L. Kirschstein National Research Service Award individual pre-doctoral MD/PhD fellowship ( F30-HL106993 ) and the Mayo Clinic Medical Scientist Training Program.
PY - 2013/10
Y1 - 2013/10
N2 - Congenital long QT syndrome (LQTS) is a genetically heterogeneous group of heritable disorders of myocardial repolarization linked by the shared clinical phenotype of QT prolongation on electrocardiogram and an increased risk of potentially life-threatening cardiac arrhythmias. At the molecular level, mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore-forming α-subunits and accessory β-subunits central to the electromechanical function of the heart have been implicated in its pathogenesis. Over the past 2 decades, our evolving understanding of the electrophysiological mechanisms by which specific genetic substrates perturb the cardiac action potential has translated into vastly improved approaches to the diagnosis, risk stratification, and treatment of patients with LQTS. In this review, we describe how our understanding of the molecular underpinnings of LQTS has yielded numerous clinically meaningful genotype-phenotype correlations and how these insights have translated into genotype- and phenotype-guided approaches to the clinical management of LQTS.
AB - Congenital long QT syndrome (LQTS) is a genetically heterogeneous group of heritable disorders of myocardial repolarization linked by the shared clinical phenotype of QT prolongation on electrocardiogram and an increased risk of potentially life-threatening cardiac arrhythmias. At the molecular level, mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore-forming α-subunits and accessory β-subunits central to the electromechanical function of the heart have been implicated in its pathogenesis. Over the past 2 decades, our evolving understanding of the electrophysiological mechanisms by which specific genetic substrates perturb the cardiac action potential has translated into vastly improved approaches to the diagnosis, risk stratification, and treatment of patients with LQTS. In this review, we describe how our understanding of the molecular underpinnings of LQTS has yielded numerous clinically meaningful genotype-phenotype correlations and how these insights have translated into genotype- and phenotype-guided approaches to the clinical management of LQTS.
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U2 - 10.1016/j.cpcardiol.2013.08.001
DO - 10.1016/j.cpcardiol.2013.08.001
M3 - Article
C2 - 24093767
AN - SCOPUS:84884804986
SN - 0146-2806
VL - 38
SP - 417
EP - 455
JO - Current Problems in Cardiology
JF - Current Problems in Cardiology
IS - 10
ER -