Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Diagnosis of congenital long QT syndrome

Stephen P Seslar, MD, PhD
Peter J Zimetbaum, MD
Charles I Berul, MD
Section Editors
John K Triedman, MD
Samuel Asirvatham, MD
Deputy Editor
Brian C Downey, MD, FACC


The 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 can lead to an increased risk of sudden cardiac death [1-3]. 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 2) [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 [6-9]. Mutations in at least 13 genes have been identified thus far in patients with genetic LQTS; the distinct genetic types are designated LQT 1 through 13 (table 1). (See "Genetics of congenital and acquired long QT syndrome".)

Two clinical phenotypes have been described in congenital LQTS that vary with the type of inheritance and the presence or absence of sensorineural hearing loss [9]:

The more common autosomal dominant form, the Romano-Ward syndrome, has a purely cardiac phenotype.

The autosomal recessive form (or compound heterozygous), the Jervell and Lange-Nielsen (JLN) syndrome, is associated with LQTS and sensorineural deafness. (See "Clinical features of congenital long QT syndrome", section on 'Congenital sensorineural deafness'.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: May 1, 2014.
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 ©2016 UpToDate, Inc.
  1. Moss AJ. Long QT Syndrome. JAMA 2003; 289:2041.
  2. Li H, Fuentes-Garcia J, Towbin JA. Current concepts in long QT syndrome. Pediatr Cardiol 2000; 21:542.
  3. 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.
  4. El-Sherif N, Turitto G. Torsade de pointes. Curr Opin Cardiol 2003; 18:6.
  5. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am 2001; 85:321.
  6. Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112:58.
  7. Wehrens XH, Vos MA, Doevendans PA, Wellens HJ. Novel insights in the congenital long QT syndrome. Ann Intern Med 2002; 137:981.
  8. Camm AJ, Janse MJ, Roden DM, et al. Congenital and acquired long QT syndrome. Eur Heart J 2000; 21:1232.
  9. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36:1.
  10. Funck-Brentano C, Jaillon P. Rate-corrected QT interval: techniques and limitations. Am J Cardiol 1993; 72:17B.
  11. Malik M. Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 2001; 12:411.
  12. Mönnig G, Eckardt L, Wedekind H, et al. Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J 2006; 27:2074.
  13. Al-Khatib SM, LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval. JAMA 2003; 289:2120.
  14. Cowan JC, Yusoff K, Moore M, et al. Importance of lead selection in QT interval measurement. Am J Cardiol 1988; 61:83.
  15. Goldman MJ. Principles of Clinical Electrocardiography, 8th ed, Lange Medical Pub, Los Altos 1973.
  16. LEPESCHKIN E, SURAWICZ B. The measurement of the Q-T interval of the electrocardiogram. Circulation 1952; 6:378.
  17. Taggart NW, Haglund CM, Tester DJ, Ackerman MJ. Diagnostic miscues in congenital long-QT syndrome. Circulation 2007; 115:2613.
  18. Garson A. The Electrogram in Infants and Children: A Systematic Approach, Lea & Febiger, Philadelphia 1983.
  19. Berul CI, Sweeten TL, Dubin AM, et al. Use of the rate-corrected JT interval for prediction of repolarization abnormalities in children. Am J Cardiol 1994; 74:1254.
  20. Rautaharju PM, Zhang ZM, Prineas R, Heiss G. Assessment of prolonged QT and JT intervals in ventricular conduction defects. Am J Cardiol 2004; 93:1017.
  21. Toivonen L. More light on QT interval measurement. Heart 2002; 87:193.
  22. Hnatkova K, Malik M. "Optimum" formulae for heart rate correction of the QT interval. Pacing Clin Electrophysiol 1999; 22:1683.
  23. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920; 7:353.
  24. Fridericia L. Die systolendauer im Elektrokardiogramm bei normalen menschen und bei herzkranken. Acta Med Scand 1920; 53:469.
  25. Moss AJ. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol 1993; 72:23B.
  26. Sagie A, Larson MG, Goldberg RJ, et al. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol 1992; 70:797.
  27. Malik M, Färbom P, Batchvarov V, et al. Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart 2002; 87:220.
  28. Manion CV, Whitsett TL, Wilson MF. Applicability of correcting the QT interval for heart rate. Am Heart J 1980; 99:678.
  29. 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.
  30. Kaufman ES, Priori SG, Napolitano C, et al. Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: experience in 101 related family members. J Cardiovasc Electrophysiol 2001; 12:455.
  31. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999; 99:529.
  32. Kligfield P, Hancock EW, Helfenbein ED, et al. Relation of QT interval measurements to evolving automated algorithms from different manufacturers of electrocardiographs. Am J Cardiol 2006; 98:88.
  33. Malfatto G, Beria G, Sala S, et al. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23:296.
  34. Zhang L, Timothy KW, Vincent GM, et al. Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes. Circulation 2000; 102:2849.
  35. Moss AJ, Zareba W, Benhorin J, et al. ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation 1995; 92:2929.
  36. Moss AJ. T-wave patterns associated with the hereditary long QT syndrome. Card Electrophysiol Rev 2002; 6:311.
  37. 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.
  38. Schwartz PJ, Malliani A. Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. Am Heart J 1975; 89:45.
  39. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88:782.
  40. Zareba W, Moss AJ, le Cessie S, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23:1541.
  41. Burattini L, Zareba W, Rashba EJ, et al. ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients. J Electrocardiol 1998; 31 Suppl:114.
  42. Shah MJ, Wieand TS, Rhodes LA, et al. QT and JT dispersion in children with long QT syndrome. J Cardiovasc Electrophysiol 1997; 8:642.
  43. Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985; 109:399.
  44. Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med 2006; 259:39.
  45. Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011; 124:2181.
  46. Hofman N, Wilde AA, Kääb S, et al. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system? Eur Heart J 2007; 28:575.
  47. Rossenbacker T, Priori SG. Clinical diagnosis of long QT syndrome: back to the caliper. Eur Heart J 2007; 28:527.
  48. Swan H, Viitasalo M, Piippo K, et al. Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol 1999; 34:823.
  49. 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.
  50. Sy RW, van der Werf C, Chattha IS, et al. Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation 2011; 124:2187.
  51. Schwartz PJ, Priori SG, Locati EH, et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation 1995; 92:3381.
  52. 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.
  53. Crotti L, Spazzolini C, Porretta AP, et al. Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol 2012; 60:2515.
  54. Walker BD, Krahn AD, Klein GJ, et al. Burst bicycle exercise facilitates diagnosis of latent long QT syndrome. Am Heart J 2005; 150:1059.
  55. 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.
  56. Eggeling T, Hoeher M, Osterhues HH, et al. Significance of noninvasive diagnostic techniques in patients with long QT syndrome. Am J Cardiol 1992; 70:1421.
  57. Eggeling T, Osterhues HH, Hoeher M, et al. Value of Holter monitoring in patients with the long QT syndrome. Cardiology 1992; 81:107.
  58. Lupoglazoff JM, Denjoy I, Berthet M, et al. Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations. Circulation 2001; 103:1095.
  59. Christiansen JL, Guccione P, Garson A Jr. Difference in QT interval measurement on ambulatory ECG compared with standard ECG. Pacing Clin Electrophysiol 1996; 19:1296.
  60. Bhandari AK, Shapiro WA, Morady F, et al. Electrophysiologic testing in patients with the long QT syndrome. Circulation 1985; 71:63.
  61. Wang DW, Yazawa K, Makita N, et al. Pharmacological targeting of long QT mutant sodium channels. J Clin Invest 1997; 99:1714.
  62. Windle JR, Geletka RC, Moss AJ, et al. Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:DeltaKPQ mutation. Ann Noninvasive Electrocardiol 2001; 6:153.
  63. Ackerman MJ, Khositseth A, Tester DJ, et al. Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clin Proc 2002; 77:413.
  64. Vyas H, Hejlik J, Ackerman MJ. Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation 2006; 113:1385.
  65. Shimizu W, Ohe T, Kurita T, Shimomura K. Differential response of QTU interval to exercise, isoproterenol, and atrial pacing in patients with congenital long QT syndrome. Pacing Clin Electrophysiol 1991; 14:1966.
  66. Katagiri-Kawade M, Ohe T, Arakaki Y, et al. Abnormal response to exercise, face immersion, and isoproterenol in children with the long QT syndrome. Pacing Clin Electrophysiol 1995; 18:2128.
  67. Viskin S, Rosso R, Rogowski O, et al. Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome. Eur Heart J 2006; 27:469.
  68. 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.
  69. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 1999; 74:1088.
  70. Batra AS, Silka MJ. Mechanism of sudden cardiac arrest while swimming in a child with the prolonged QT syndrome. J Pediatr 2002; 141:283.
  71. Choi G, Kopplin LJ, Tester DJ, et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110:2119.
  72. Yoshinaga M, Kamimura J, Fukushige T, et al. Face immersion in cold water induces prolongation of the QT interval and T-wave changes in children with nonfamilial long QT syndrome. Am J Cardiol 1999; 83:1494.
  73. Kamimura J, Yoshinaga M, Kono Y, et al. A simple method for evaluating abnormal lengthening of the QT interval during the face immersion test. Pediatr Cardiol 2002; 23:122.
  74. Priori SG, Barhanin J, Hauer RN, et al. Genetic and molecular basis of cardiac arrhythmias: impact on clinical management parts I and II. Circulation 1999; 99:518.
  75. Priori SG, Barhanin J, Hauer RN, et al. Genetic and molecular basis of cardiac arrhythmias: impact on clinical management part III. Circulation 1999; 99:674.
  76. 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.
  77. 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.
  78. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 2011; 8:1308.