1887
Volume 2015, Issue 2
  • ISSN: 2305-7823
  • E-ISSN:

Abstract

Congenital long QT syndrome, caused by a cardiac channelopathy, is a leading cause of sudden cardiac death in the young population. In total, 16 genes have been implicated in this condition, with three genes being the most commonly affected. Long QT syndrome is one of the earliest conditions for which a genotype specific treatment was designed. This genotype-phenotype correlation extends to involve the clinical presentation, electrocardiographic manifestation and treatment strategies. It is necessary for the clinician treating these patients to be cognizant of the important role played by the genotype in order to best provide counseling and treatment options to this unique population.

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2015-07-04
2019-08-20
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References

  1. [1]. Schwartz   PJ., , Stramba-Badiale   M., , Crotti   L., , Pedrazzini   M., , Besana   A., , Bosi   G., , Gabbarini   F., , Goulene   K., , Insolia   R., , Mannarino   S., , Mosca   F., , Nespoli   L., , Rimini   A., , Rosati   E., , Salice   P., , Spazzolini   C. . Prevalence of the congenital long-QT syndrome. . Circulation . 2009; ;120: : 1761– 1767 .
    [Google Scholar]
  2. [2]. Tester   DJ., , Ackerman   MJ. . Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. . J Am Coll Cardiol . 2007; ;49: : 240– 246 .
    [Google Scholar]
  3. [3]. Schwartz   PJ., , Crotti   L., , Insolia   R., , Long   QT. . syndrome: from genetics to management. . Circ Arrhythm Electrophysiol . 2012; ;5: : 868– 877 .
    [Google Scholar]
  4. [4]. Schwartz   PJ., , Ackerman   MJ. . The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. . Eur Heart J . 2013; ;34: : 3109– 3116 .
    [Google Scholar]
  5. [5]. Schwartz   PJ., , Crotti   L. . QTc behavior during exercise and genetic testing for the long-QT syndrome. . Circulation Nov . 2011; ;124: 20 : 2181– 2184 .
    [Google Scholar]
  6. [6]. Amin   AS., , Tan   HL., , Wilde   AA. . Cardiac ion channels in health and disease. . Heart Rhythm . 2010; ;7: : 117– 1126 .
    [Google Scholar]
  7. [7]. Schwartz   PJ., , Ackerman   MJ., , George   AL Jr., , Wilde   AA. . Impact of genetics on the clinical management of channelopathies. . J Am Coll Cardiol . 2013; ;62: : 169– 180 .
    [Google Scholar]
  8. [8]. Tester   DJ., , Ackerman   MJ. . Genetics of Long QT syndrome. . Methodist Debakey Cardiovasc J . 2014; ;10: : 29– 33 .
    [Google Scholar]
  9. [9]. Tristani-Firouzi   M1., , Jensen   JL., , Donaldson   MR., , Sansone   V., , Meola   G., , Hahn   A., , Bendahhou   S., , Kwiecinski   H., , Fidzianska   A., , Plaster   N., , Fu   YH., , Ptacek   LJ., , Tawil   R. . Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). . J Clin Invest . 2002; ;110: : 381– 388 .
    [Google Scholar]
  10. [10]. Mohler   PJ., , Splawski   I., , Napolitano   C., , Bottelli   G., , Sharpe   L., , Timothy   K., , Priori   SG., , Keating   MT., , Bennett   VA. . cardiac arrhythmia syndrome caused by loss of ankyrin-B function. . Proc Nat Acad Sci . 2004; ;101: : 9137– 9142 .
    [Google Scholar]
  11. [11]. Zareba   W. . Genotype-specific ECG patterns in long QT syndrome. . J Electrocardiol . 2006; ;39: : S101– S106 .
    [Google Scholar]
  12. [12]. Moss   AJ1., , Zareba   W., , Benhorin   J., , Locati   EH., , Hall   WJ., , Robinson   JL., , Schwartz   PJ., , Towbin   JA., , Vincent   GM., , Lehmann   MH. . ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. . Circulation . 1995; ;92: : 2929– 2934 .
    [Google Scholar]
  13. [13]. Antzelevitch   C. . Molecular genetics of arrhythmias and cardiovascular conditions associated with arrhythmias. . J Cardiovasc Electrophysiol . 2003; ;14: : 1259– 1272 .
    [Google Scholar]
  14. [14]. Zhang   L., , Timothy   KW., , Vincent   GM., , Lehmann   MH., , Fox   J., , Giuli   LC., , Shen   J., , Splawski   I., , Priori   SG., , Compton   SJ., , Yanowitz   F., , Benhorin   J., , Moss   AJ., , Schwartz   PJ., , Robinson   JL., , Wang   Q., , Zareba   W., , Keating   MT., , Towbin   JA., , Napolitano   C., , Medina   A. . Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes. . Circulation . 2000; ;102: : 2849– 2855 .
    [Google Scholar]
  15. [15]. Priori   SG., , Napolitano   C., , Schwartz   PJ. . Low penetrance in the long-QT syndrome: clinical impact. . Circulation . 1999; ;99: : 529– 533 .
    [Google Scholar]
  16. [16]. Sy   RW., , van der Werf   C., , Chatta   IS., , Chockalingam   P., , Adler   A., , Healey   JS., , Perrin   M., , Gollob   MH., , Skanes   AC., , Yee   R., , Gula   LJ., , Leong –Sit   P., , Viskin   S., , Klein   GJ., , Wilde   AA., , Krahn   AD. . Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. . Circulation . 2011; ;124: : 2187– 2194 .
    [Google Scholar]
  17. [17]. Aziz   PF., , Wieand   TS., , Ganley   J., , Henderson   J., , Patel   AR., , Iyer   VR., , Vogel   RL., , McBride   M., , Vetter   VL., , Shah   MJ. . Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome. . Circ Arrhythm Electrophysiol . 2011; ;4: : 867– 873 .
    [Google Scholar]
  18. [18]. Schwartz   PJ., , Priori   SG., , Spazzolini   C., , Moss   AJ., , Vincent   GM., , Napoli- tano   C., , Denjoy   I., , Guicheney   P., , Breithardt   G., , Keating   MT., , Towbin   JA., , Beggs   AH., , Brink   P., , Wilde   AA., , Toivonen   L., , Zareba   W., , Robinson   JL., , Timothy   KW., , Corfield   V., , Wattanasirichaigoon   D., , Corbett   C., , Haverkamp   W., , Schulze-Bahr   E., , Lehmann   MH., , Schwartz   K., , Coumel   P., , Bloise   R. . Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. . Circulation . 2001; ;89:95 .
    [Google Scholar]
  19. [19]. Wilde   AA., , Jongbloed   RJ., , Doevendans   PA., , Düren   DR., , Hauer   RN., , van Langen   IM., , van Tintelen   JP., , Smeets   HJ., , Meyer   H., , Geelen   JL. . 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– 332 .
    [Google Scholar]
  20. [20]. Khositseth   A., , Tester   DJ., , Will   ML., , Bell   CM., , Ackerman   MJ. . Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. . Heart Rhythm . 2004; ;1: : 60– 64 .
    [Google Scholar]
  21. [21]. Stramba-Badiale   M., , Priori   SG., , Napolitano   C., , Locati   EH., , Viñolas   X., , Haverkamp   W., , Schulze-Bahr   E., , Goulene   K., , Schwartz   PJ. . Gene-specific differences in the circadian variation of ventricular repolarization in the long QT syndrome: a key to sudden death during sleep?.   Ital Heart J . 2000; ;1: : 323– 328 .
    [Google Scholar]
  22. [22]. Priori   SG., , Schwartz   PJ., , Napolitano   C., , Bloise   R., , Ronchetti   E., , Grillo   M., , Vicentini   A., , Spazzolini   C., , Nastoli   J., , Bottelli   G., , Folli   R., , Cappelletti   D. . Risk stratification in the long-QT syndrome. . N Engl J Med . 2003; ;348: : 1866– 1874 .
    [Google Scholar]
  23. [23]. Schwartz   PJ., , Spazzolini   C., , Crotti   L., , Bathen   J., , Amlie   JP., , Timothy   K., , Shkolnikova   M., , Berul   CI., , Bitner-Glindzicz   M., , Toivonen   L., , Horie   M., , Schulze-Bahr   E., , Denjoy   I. . The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. . Circulation . 2006; ;113: : 783– 790 .
    [Google Scholar]
  24. [24]. Mullally   J1., , Goldenberg   I., , Moss   AJ., , Lopes   CM., , Ackerman   MJ., , Zareba   W., , McNitt   S., , Robinson   JL., , Benhorin   J., , Kaufman   ES., , Towbin   JA., , Barsheshet   A. . Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. . Heart Rhythm . 2013; ;10: : 378– 382 .
    [Google Scholar]
  25. [25]. Barsheshet   A., , Goldenberg   I., , O-Uchi   J., , Moss   AJ., , Jons   C., , Shimizu   W., , Wilde   AA., , McNitt   S., , Peterson   DR., , Zareba   W., , Robinson   JL., , Ackerman   MJ., , Cypress   M., , Gray   DA., , Hofman   N., , Kanters   JK., , Kaufman   ES., , Platonov   PG., , Qi   M., , Towbin   JA., , Vincent   GM., , Lopes   CM. . Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. . Circulation . 2012; ;125: : 1988– 1996 .
    [Google Scholar]
  26. [26]. Johnson   JN., , Ackerman   MJ. . Return to play? Athletes with congenital long QT syndrome. . Br J Sports Med . 2013; ;47: : 28– 33 .
    [Google Scholar]
  27. [27]. Schwartz   PJ. . Management of long QT syndrome. . Nat Clin Pract Cardiovasc Med . 2005; ;2: : 346– 351 .
    [Google Scholar]
  28. [28]. Chockalingam   P., , Crotti   L., , Girardengo   G., , Johnson   JN., , Harris   KM., , van der Heijden   JF., , Hauer   RNW., , Beckmann   BM., , Spazzolini   C., , Rordorf   R., , Rydberg   A., , Clur   SAB., , Paed   FCP., , Fischer   M., , van den Heuvel   F., , Kääb   S., , Blom   NA., , Ackerman   MJ., , Schwartz   PJ., , Wilde   AAM. . Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. . J Am Coll Cardiol . 2012; ;2092: : 2099 .
    [Google Scholar]
  29. [29]. Priori   SG., , Napolitano   C., , Schwartz   PJ., , Grillo   M., , Bloise   R., , Ronchetti   E., , Moncalvo   C., , Tulipani   C., , Veia   A., , Bottelli   G., , Nastoli   J. . Association of long QT syndrome loci and cardiac events among patients treated with beta- blockers. . JAMA . 2004; ;292: : 1341– 1344 .
    [Google Scholar]
  30. [30]. Ruan   Y., , Liu   N., , Bloise   R., , Napolitano   C., , Priori   SG. . Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. . Circulation . 2007; ;116: : 1137– 1144 .
    [Google Scholar]
  31. [31]. Moss   AJ., , Zareba   W., , Schwarz   KQ., , Rosero   S., , McNitt   S., , Robinson   JL. . Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. . J Cardiovasc Electrophysiol . 2008; ;19: : 1289– 1293 .
    [Google Scholar]
  32. [32]. Schwartz   PJ., , Spazzolini   C., , Priori   SG., , Crotti   L., , Vicentini   A., , Landolina   M., , Gasparini   M., , Wilde   AAM., , Knops   RE., , Denjoy   I., , Toivonen   L., , Mönnig   G., , Al-Fayyadh   M., , Jordaens   L., , Borggrefe   M., , Holmgren   C., , Brugada   P., , De Roy   L., , Hohnloser   SH., , Brink   PA. . Who are the long-QT syndrome patients who receive an implantable cardioverter defibrillator and what happens to them? Data from the European long-QT syndrome implantable cardioverter-defibrillator (LQTS ICD) Registry. . Circulation . 2010; ;122: : 1272– 1282 .
    [Google Scholar]
  33. [33]. Schwartz   PJ. . Cardiac sympathetic denervation to prevent life-threatening arrhythmias. . Nat Rev Cardiol . 2014; ;11: : 346– 353 .
    [Google Scholar]
  34. [34]. Earle   N., , Yeo Han   D., , Pilbrow   A., , Crawford   J., , Smith   W., , Shelling   AN., , Cameron   V., , Love   DR., , Skinner   JR. . Single nucleotide polymorphisms in arrhythmia genes modify the risk of cardiac events and sudden death in long QT syndrome. . Heart Rhythm . 2014; ;11: : 76– 82 .
    [Google Scholar]
  35. [35]. Itzhaki   I., , Maizels   L., , Huber   I., , Zwi-Dantsis   L., , Caspi   O., , Winterstern   A., , Feldman   O., , Gepstein   A., , Arbel   G., , Hammerman   H., , Boulos   M., , Gepstein   L. . Modelling the long QT syndrome with induced pluripotent stem cells. . Nature . 2011; ;471: : 225– 229 .
    [Google Scholar]
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  • Article Type: Review Article
Keyword(s): genotype , genotype association studies and Long QT syndrome
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