title: Genetic biomarkers for the risk of seizures in long QT syndrome.
abstract: OBJECTIVE
  The coprevalence, severity, and biomarkers for seizures and arrhythmias in long QT syndrome (LQTS) remain incompletely understood.
  
  
  METHODS
  Using the Rochester-based LQTS Registry, this study included large cohorts of LQTS1-3 participants (LQTS+, n = 965) and those without a LQTS mutation (LQTS-, n = 936).
  
  
  RESULTS
  Compared to LQTS-participants, there was a higher prevalence of LQTS1, LQTS2, and LQTS+participants classified as having seizures (p < 0.001, i.e., history of seizures/epilepsy or antiseizure medication). LQTS+participants with longer corrected QT interval (QTc) durations were more likely to have seizures. LQTS2 mutations in the KCNH2 pore domain were positive predictors for both arrhythmias and seizures. In contrast, mutations in the cyclic nucleotide binding domain (cNBD) of KCNH2 conferred a negative risk of seizures, but not arrhythmias. LQTS2, KCNH2-pore, KCNH2-cNBD, QTcduration, and sex were independent predictors of seizures. LQTS+participants with seizures had significantly longer QTcdurations, and a history of seizures was the strongest independent predictor of arrhythmias (hazard ratio 4.09, 95% confidence interval 2.63-6.36, p < 0.001).
  
  
  CONCLUSIONS
  This study highlights potential biomarkers for neurocardiac electrical abnormalities in LQTS.
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY. david_auerbach@urmc.rochester.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Auerbach
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gross
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dirksen
authors.affiliation: From the Department of Medicine, Aab Cardiovascular Research Institute (D.S.A.), Department of Medicine, Heart Research Follow-up Program (S.M., W.Z., A.J.M.), and Departments of Neurology (R.A.G.) and Pharmacology & Physiology (R.A.G., R.T.D.), University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000328:Adult; D015331:Cohort Studies; D000072237:ERG1 Potassium Channel / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation; D015995:Prevalence; D012042:Registries; D012306:Risk; D012307:Risk Factors; D012640:Seizures / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D005819:Genetic Markers; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human