title: Genetics of long QT syndrome.
abstract: Long QT syndrome (LQTS) is a potentially life-threatening cardiac arrhythmia characterized by delayed myocardial repolarization that produces QT prolongation and increased risk for torsades des pointes (TdP)-triggered syncope, seizures, and sudden cardiac death (SCD) in an otherwise healthy young individual with a structurally normal heart. Currently, there are three major LQTS genes (KCNQ1, KCNH2, and SCN5A) that account for approximately 75% of the disorder. For the major LQTS genotypes, genotype-phenotype correlations have yielded gene-specific arrhythmogenic triggers, electrocardiogram (ECG) patterns, response to therapies, and intragenic and increasingly mutation-specific risk stratification. The 10 minor LQTS-susceptibility genes collectively account for less than 5% of LQTS cases. In addition, three atypical LQTS or multisystem syndromic disorders that have been associated with QT prolongation have been described, including ankyrin-B syndrome, Anderson-Tawil syndrome (ATS), and Timothy syndrome (TS). Genetic testing for LQTS is recommended in patients with either a strong clinical index of suspicion or persistent QT prolongation despite their asymptomatic state. However, genetic test results must be interpreted carefully.
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tester
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: genetics; ion channel; long QT syndrome