Long QT Syndrome: from Molecular Biology to Clinical Management

  • P. J. Schwartz


The last few years have witnessed a dramatic progress in the molecular biology of the congenital long QT syndrome (LQTS). The impact of these discoveries on the understanding of LQTS, and also of other diseases in which control of the cardiac action potential is important, has been recently reviewed by a multidisciplinary task force [1]. This progress has largely resulted from the partnership between molecular biologists and the clinical investigators who had made available the extraordinarily large number of LQTS families with a very well characterized phenotype enrolled in the International Registry co-ordinated by Moss and Schwartz.


Heart Rate Increase Ventricular Repolarization Cardiac Action Potential Cardiac Sodium Channel LQT3 Patient 
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  1. 1.
    Roden DM, Lazzara R, Rosen MR, Schwartz PJ, Towbin JA, Vincent GM for the SADS Foundation Task Force on LQTS (1996) Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. Circulation 94: 1996–2012Google Scholar
  2. 2.
    Towbin JA, Li H, Taggart RT, Lehmann MH, Schwartz PJ, Satler CA, Ayyagari R, Robinson JL, Moss AJ, Hejtmancik JF (1994) Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families. Circulation 90: 2635–2644PubMedCrossRefGoogle Scholar
  3. 3.
    Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) KvLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature 384: 78–80PubMedCrossRefGoogle Scholar
  4. 4.
    Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT (1996) Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IK, potassium channel. Nature 384: 80–83PubMedCrossRefGoogle Scholar
  5. 5.
    Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J, Faure S, Gary F, Coumel P, Petit C, Schwartz K, Guicheney P (1997) A novel mutation in the potassium channel KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nature Genetics 15: 186–189PubMedCrossRefGoogle Scholar
  6. 6.
    Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80: 805–811PubMedCrossRefGoogle Scholar
  7. 7.
    Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MTGoogle Scholar
  8. (1995).
    Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet 4:1603–1607Google Scholar
  9. 8.
    Bennett PB, Yazawa K, Makita N, George AL Jr (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376: 683–685PubMedCrossRefGoogle Scholar
  10. 9.
    Dumaine R, Wang Q, Keating MT, Hartmann HA, Schwartz PJ, Brown AM, Kirsch GE (1996) Multiple mechanisms of Na+ channel-linked long-QT syndrome. Circ Res 78: 916–924PubMedCrossRefGoogle Scholar
  11. 10.
    An RH, Bangalore R, Rosero SZ, Kass RS (1996) Lidocaine block of LQT-3 mutant human Na+ channels. Circ Res 79: 103–108PubMedCrossRefGoogle Scholar
  12. 11.
    Sanguinetti C, Curran ME, Spector PS, Keating MT (1996) Spectrum of HERG K+ -channel dysfunction in an inherited cardiac arrhythmia. Proc Natl Acad Sci USA 93: 22082212Google Scholar
  13. 12.
    Moss AJ, Zareba W, Benhorin J, Locati EH, Hall WJ, Robinson JL, Schwartz PJ, Towbin JA, Vincent GM, Lehmann MH, Keating MT, MacCluer JW, Timothy KW (1995) ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation 92: 2929–2934PubMedCrossRefGoogle Scholar
  14. 13.
    Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantù F, Towbin AJ, Keating MT, Hammoude H, Brown AM, Chen LK, Colatsky TJ (1995) Long QT syndrome patients with mutations on the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation 92: 3381–3386Google Scholar
  15. 14.
    Priori SG, Napolitano C, Cantù F, Brown AM, Schwartz PJ (1996) Differential response to Na+ channel blockade, (3-adrenergic stimulation, and rapid pacing in a cellular model mimicking the SCN5A and HERG defects present in the long QT syndrome. Circ Res 78: 1009–1015PubMedCrossRefGoogle Scholar
  16. 15.
    Schwartz PJ, Moss AJ, Priori SG, Robinson JL, Napolitano C, Paganini V, Lehmann MH, Vincent GM, Keating MT, Towbin JA (1997) Gene-specific influence on the triggers for syncope and sudden death in long QT syndrome. Eur Heart J (in press) (abstr)Google Scholar
  17. 16.
    Compton SJ, Lux RL, Ramsey MR, Strelich KT, Sanguinetti MC, Green LS, Keating MT, Mason JW (1996) Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation 94: 1018–1022Google Scholar
  18. 17.
    Schwartz PJ (1997)The long QT syndrome. In: Camm AJ (ed) clinical approaches to tachyarrhythmias series. Futura Publishing Co, Armonk, NYGoogle Scholar

Copyright information

© Springer-Verlag Italia 1998

Authors and Affiliations

  • P. J. Schwartz
    • 1
  1. 1.Università degli Studi di Pavia, Policlinico S. Matteo IRCCSPaviaItaly

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