UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Congenital long QT syndrome: Epidemiology and clinical manifestations

Authors
Peter J Schwartz, MD
Michael J Ackerman, MD, PhD
Section Editors
John K Triedman, MD
Samuel Asirvatham, MD
Deputy Editor
Brian C Downey, MD, FACC

INTRODUCTION

Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram (ECG) (waveform 1) that can lead to symptomatic ventricular arrhythmias and an increased risk of sudden cardiac death [1,2]. The primary symptoms in patients with LQTS include syncope, seizures, and cardiac arrest. This syndrome is associated with an increased risk of a characteristic life-threatening cardiac arrhythmia known as torsades de pointes or "twisting of the points" (waveform 2A-B) [3,4].

LQTS may be congenital or acquired [1,5]. Mutations in at least 17 genes have been identified thus far in patients with congenital LQTS (table 1) [5]. Acquired LQTS usually results from undesired QT prolongation and potential for QT-triggered arrhythmias by either QT-prolonging disease states, QT-prolonging medications (www.crediblemeds.org), or QT-prolonging electrolyte disturbances (table 2) [6]. (See "Genetics of congenital and acquired long QT syndrome".)

While mutations in numerous genes have been identified in patients with congenital LQTS, 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 [7]. (See 'Congenital sensorineural deafness' below.)

                        
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:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 04, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Schwartz PJ, Ackerman MJ. The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. Eur Heart J 2013; 34:3109.
  2. Moss AJ. Long QT Syndrome. JAMA 2003; 289:2041.
  3. El-Sherif N, Turitto G. Torsade de pointes. Curr Opin Cardiol 2003; 18:6.
  4. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am 2001; 85:321.
  5. Schwartz PJ, Ackerman MJ, George AL Jr, Wilde AAM. Impact of genetics on the clinical management of channelopathies. J Am Coll Cardiol 2013; 62:169.
  6. Schwartz PJ, Woosley RL. Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes. J Am Coll Cardiol 2016; 67:1639.
  7. 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.
  8. Schwartz PJ, Stramba-Badiale M, Crotti L, et al. Prevalence of the congenital long-QT syndrome. Circulation 2009; 120:1761.
  9. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999; 99:529.
  10. 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.
  11. Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991; 84:1136.
  12. Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003; 348:1866.
  13. 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.
  14. Pfammatter JP, Donati F, Dürig P, et al. Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation. Acta Paediatr 1995; 84:569.
  15. Singh B, al Shahwan SA, Habbab MA, et al. Idiopathic long QT syndrome: asking the right question. Lancet 1993; 341:741.
  16. 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.
  17. Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112:58.
  18. Gorgels AP, Al Fadley F, Zaman L, et al. The long QT syndrome with impaired atrioventricular conduction: a malignant variant in infants. J Cardiovasc Electrophysiol 1998; 9:1225.
  19. Vincent GM. The heart rate of Romano-Ward syndrome patients. Am Heart J 1986; 112:61.
  20. Beinder E, Grancay T, Menéndez T, et al. Fetal sinus bradycardia and the long QT syndrome. Am J Obstet Gynecol 2001; 185:743.
  21. 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.
  22. Mitchell JL, Cuneo BF, Etheridge SP, et al. Fetal heart rate predictors of long QT syndrome. Circulation 2012; 126:2688.
  23. 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.
  24. 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.
  25. Johnson JN, Tester DJ, Perry J, et al. Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. Heart Rhythm 2008; 5:704.
  26. 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.
  27. 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.
  28. 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.
  29. Davis AM, Wilkinson JL. The long QT syndrome and seizures in childhood. J Paediatr Child Health 1998; 34:410.
  30. 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.
  31. Wehrens XH, Vos MA, Doevendans PA, Wellens HJ. Novel insights in the congenital long QT syndrome. Ann Intern Med 2002; 137:981.
  32. 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.
  33. 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.
  34. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 1999; 74:1088.
  35. Choi G, Kopplin LJ, Tester DJ, et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110:2119.
  36. 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.
  37. 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.
  38. 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.
  39. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36:1.
  40. 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.
  41. 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.
  42. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet 1999; 89:137.
  43. 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.
  44. 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.
  45. 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.
  46. Ackerman MJ, Siu BL, Sturner WQ, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 2001; 286:2264.
  47. Arnestad M, Crotti L, Rognum TO, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation 2007; 115:361.
  48. Wang DW, Desai RR, Crotti L, et al. Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation 2007; 115:368.
  49. Crotti L, Tester DJ, White WM, et al. Long QT syndrome-associated mutations in intrauterine fetal death. JAMA 2013; 309:1473.
  50. Andersen ED, Krasilnikoff PA, Overvad H. Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome? Acta Paediatr Scand 1971; 60:559.
  51. 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.
  52. Sansone V, Griggs RC, Meola G, et al. Andersen's syndrome: a distinct periodic paralysis. Ann Neurol 1997; 42:305.
  53. 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.
  54. 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.
  55. Marks ML, Trippel DL, Keating MT. Long QT syndrome associated with syndactyly identified in females. Am J Cardiol 1995; 76:744.
  56. Krause U, Gravenhorst V, Kriebel T, et al. A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). Clin Res Cardiol 2011; 100:1123.
  57. Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004; 119:19.