Clinical features of congenital long QT syndrome
- Peter J Zimetbaum, MD
Peter J Zimetbaum, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Harvard Medical School
- Charles I Berul, MD
Charles I Berul, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Pediatrics
- George Washington University
- Section Editors
- John K Triedman, MD
John K Triedman, MD
- Section Editor — Pediatric Cardiology
- Professor of Pediatrics
- Harvard Medical School
- Samuel Lévy, MD
Samuel Lévy, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Cardiology
- University of Marseille, France
- Samuel Asirvatham, MD
Samuel Asirvatham, MD
- Section Editor — Long QT Syndrome
- Professor of Medicine and Pediatrics
- Mayo Clinic College of Medicine
The long QT syndrome (LQTS) is a disorder of myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram (ECG) (waveform 1) and an increased risk of sudden cardiac death [1-3]. This syndrome is associated with an increased risk of a characteristic life-threatening polymorphic ventricular tachycardia known as torsades de pointes or "twisting of the points" (waveform 2A-B) [4,5]. The primary symptoms in patients with LQTS include palpitations, syncope, seizures, and cardiac arrest.
The long QT syndrome may be congenital or acquired. While mutations in numerous genes have been identified in patients with congenital LQTS (table 1), two clinical phenotypes have been described that differ in the type of inheritance and the presence or absence of sensorineural hearing loss :
●The more common autosomal dominant form, the Romano-Ward syndrome, has a purely cardiac phenotype. (See "Genetics of congenital and acquired long QT syndrome".)
●The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, is associated with LQTS and sensorineural deafness, and a more malignant clinical course . (See 'Congenital sensorineural deafness' below.)
The epidemiology, clinical features, and conditions that are associated with congenital LQTS will be reviewed here. The diagnosis and management of congenital LQTS in children and adults and the clinical features of acquired LQTS are discussed separately. (See "Congenital long QT syndrome: Diagnosis" and "Prognosis and management of congenital long QT syndrome" and "Acquired long QT syndrome".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Moss AJ. Long QT Syndrome. JAMA 2003; 289:2041.
- Li H, Fuentes-Garcia J, Towbin JA. Current concepts in long QT syndrome. Pediatr Cardiol 2000; 21:542.
- Jackman WM, Friday KJ, Anderson JL, et al. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988; 31:115.
- El-Sherif N, Turitto G. Torsade de pointes. Curr Opin Cardiol 2003; 18:6.
- Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am 2001; 85:321.
- Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36:1.
- Schwartz PJ, Spazzolini C, Crotti L, et al. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 2006; 113:783.
- Quaglini S, Rognoni C, Spazzolini C, et al. Cost-effectiveness of neonatal ECG screening for the long QT syndrome. Eur Heart J 2006; 27:1824.
- Schwartz PJ, Stramba-Badiale M, Crotti L, et al. Prevalence of the congenital long-QT syndrome. Circulation 2009; 120:1761.
- Earle N, Crawford J, Smith W, et al. Community detection of long QT syndrome with a clinical registry: an alternative to ECG screening programs? Heart Rhythm 2013; 10:233.
- Goldenberg I, Zareba W, Moss AJ. Long QT Syndrome. Curr Probl Cardiol 2008; 33:629.
- Napolitano C, Priori SG, Schwartz PJ, et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA 2005; 294:2975.
- Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med 1992; 327:846.
- Berul CI, Sweeten TL, Hill SL, Vetter VL. Provocative testing in children with suspect congenital long QT syndrome. Ann Noninvasive Electrocardiol 1998; 3:3.
- Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112:58.
- Wehrens XH, Vos MA, Doevendans PA, Wellens HJ. Novel insights in the congenital long QT syndrome. Ann Intern Med 2002; 137:981.
- Camm AJ, Janse MJ, Roden DM, et al. Congenital and acquired long QT syndrome. Eur Heart J 2000; 21:1232.
- Haverkamp W, Breithardt G, Camm AJ, et al. The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J 2000; 21:1216.
- Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932.
- Garson A Jr, Dick M 2nd, Fournier A, et al. The long QT syndrome in children. An international study of 287 patients. Circulation 1993; 87:1866.
- Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991; 84:1136.
- Pacia SV, Devinsky O, Luciano DJ, Vazquez B. The prolonged QT syndrome presenting as epilepsy: a report of two cases and literature review. Neurology 1994; 44:1408.
- Pfammatter JP, Donati F, Dürig P, et al. Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation. Acta Paediatr 1995; 84:569.
- Singh B, al Shahwan SA, Habbab MA, et al. Idiopathic long QT syndrome: asking the right question. Lancet 1993; 341:741.
- Bardai A, Blom MT, van Noord C, et al. Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications. Heart 2015; 101:17.
- Davis AM, Wilkinson JL. The long QT syndrome and seizures in childhood. J Paediatr Child Health 1998; 34:410.
- Peeters CM, Wijnberger DE, Kamphuis DJ, et al. How reliable is asking the "right question" in diagnosing idiopathic long QT syndrome? Lancet 1995; 345:925.
- Vincent GM. The heart rate of Romano-Ward syndrome patients. Am Heart J 1986; 112:61.
- Beinder E, Grancay T, Menéndez T, et al. Fetal sinus bradycardia and the long QT syndrome. Am J Obstet Gynecol 2001; 185:743.
- Lupoglazoff JM, Denjoy I, Villain E, et al. Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol 2004; 43:826.
- Mitchell JL, Cuneo BF, Etheridge SP, et al. Fetal heart rate predictors of long QT syndrome. Circulation 2012; 126:2688.
- Veldkamp MW, Wilders R, Baartscheer A, et al. Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res 2003; 92:976.
- Kirchhof P, Eckardt L, Franz MR, et al. Prolonged atrial action potential durations and polymorphic atrial tachyarrhythmias in patients with long QT syndrome. J Cardiovasc Electrophysiol 2003; 14:1027.
- Johnson JN, Tester DJ, Perry J, et al. Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. Heart Rhythm 2008; 5:704.
- Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001; 103:89.
- Wilde AA, Jongbloed RJ, Doevendans PA, et al. Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). J Am Coll Cardiol 1999; 33:327.
- Moss AJ, Robinson JL, Gessman L, et al. Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome. Am J Cardiol 1999; 84:876.
- Splawski I, Shen J, Timothy KW, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000; 102:1178.
- Takenaka K, Ai T, Shimizu W, et al. Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome. Circulation 2003; 107:838.
- Batra AS, Silka MJ. Mechanism of sudden cardiac arrest while swimming in a child with the prolonged QT syndrome. J Pediatr 2002; 141:283.
- Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 1999; 74:1088.
- Choi G, Kopplin LJ, Tester DJ, et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110:2119.
- Ali RH, Zareba W, Moss AJ, et al. Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome. Am J Cardiol 2000; 85:457.
- Tan HL, Bardai A, Shimizu W, et al. Genotype-specific onset of arrhythmias in congenital long-QT syndrome: possible therapy implications. Circulation 2006; 114:2096.
- Yang P, Kanki H, Drolet B, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002; 105:1943.
- Duggal P, Vesely MR, Wattanasirichaigoon D, et al. Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome. Circulation 1998; 97:142.
- Huang L, Bitner-Glindzicz M, Tranebjaerg L, Tinker A. A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome. Cardiovasc Res 2001; 51:670.
- Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet 1999; 89:137.
- Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J 1975; 89:378.
- Tuncer C, Cokkeser Y, Komsuoglu B, et al. Assessment of ventricular repolarization in deaf-mute children. Pediatr Cardiol 2000; 21:135.
- Ocal B, Imamoglu A, Atalay S, Ercan Tutar H. Prevalence of idiopathic long QT syndrome in children with congenital deafness. Pediatr Cardiol 1997; 18:401.
- Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998; 338:1709.
- Schwartz PJ, Priori SG, Dumaine R, et al. A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med 2000; 343:262.
- Wedekind H, Smits JP, Schulze-Bahr E, et al. De novo mutation in the SCN5A gene associated with early onset of sudden infant death. Circulation 2001; 104:1158.
- Ackerman MJ, Siu BL, Sturner WQ, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 2001; 286:2264.
- Arnestad M, Crotti L, Rognum TO, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation 2007; 115:361.
- Wang DW, Desai RR, Crotti L, et al. Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation 2007; 115:368.
- Crotti L, Tester DJ, White WM, et al. Long QT syndrome-associated mutations in intrauterine fetal death. JAMA 2013; 309:1473.
- Guntheroth WG, Spiers PS. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998; 339:1161; author reply 1162.
- Andersen ED, Krasilnikoff PA, Overvad H. Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome? Acta Paediatr Scand 1971; 60:559.
- Tristani-Firouzi M, Jensen JL, Donaldson MR, et al. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002; 110:381.
- Sansone V, Griggs RC, Meola G, et al. Andersen's syndrome: a distinct periodic paralysis. Ann Neurol 1997; 42:305.
- Zhang L, Benson DW, Tristani-Firouzi M, et al. Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation 2005; 111:2720.
- Marks ML, Whisler SL, Clericuzio C, Keating M. A new form of long QT syndrome associated with syndactyly. J Am Coll Cardiol 1995; 25:59.
- Marks ML, Trippel DL, Keating MT. Long QT syndrome associated with syndactyly identified in females. Am J Cardiol 1995; 76:744.
- Bondy CA, Van PL, Bakalov VK, et al. Prolongation of the cardiac QTc interval in Turner syndrome. Medicine (Baltimore) 2006; 85:75.
- Bondy CA, Ceniceros I, Van PL, et al. Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome. Pediatrics 2006; 118:e1220.
- Dalla Pozza R, Bechtold S, Urschel S, et al. QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG. Eur J Pediatr 2009; 168:59.
- Trolle C, Mortensen KH, Pedersen LN, et al. Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations. PLoS One 2013; 8:e69614.
- CLINICAL MANIFESTATIONS
- TYPES OF ARRHYTHMIAS
- Polymorphic VT/torsades de pointes
- AV block
- Atrial arrhythmias
- TRIGGERS OF ARRHYTHMIA
- External triggers
- Pause dependence
- Influence of genotype on triggers
- Medications and electrolyte abnormalities
- ASSOCIATED CONDITIONS
- Congenital sensorineural deafness
- - Recommendations for screening ECG in congenital sensorineural deafness
- Sudden infant death syndrome
- - Recommendations for ECG screening in infants
- Andersen syndrome
- Turner syndrome
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS