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Europace 2001 3(1):16-27; doi:10.1053/eupc.2000.0141
© 2001 by European Society of Cardiology
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REGULAR ARTICLE: MOLECULAR AND GENETIC BASIS OF ELECTROPHYSIOLOGICAL DISEASE

The long QT syndrome

S. G. Priori, R. Bloise and L. Crotti

Molecular Cardiology Laboratories, Fondazione Salvatore Maugeri IRCCS Pavia Policlinico S. Matteo IRCCS Pavia, Italy


Correspondence: S. G. Priori, MD, PhD, Molecular Cardiology Laboratories, Fondazione Salvatore Maugeri, IRCCS, Via Ferrata, 8 27100 Pavia, Italy. E-mail: spriori{at}fsm.it


[1] Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985; 109: 399–411.[CrossRef][Web of Science][Medline]

[2] Schwartz PJ, Locati EH, Napolitano C, Priori SG. The long QT syndrome. In Zipes DP and Jalife J (Eds.). Cardiac Electrophysiology. From Cell to Bedside 1995; 2nd Edition Philadelphia W.B. Saunders pp. 788–811.

[3] Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell'età pediatrica. La Clinica Pediatrica 1963; 45: 656–683.[Medline]

[4] Ward OC. A new familial cardiac syndrome in children. J Irish Med Ass 1964; 54: 103–106.

[5] Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J 1975; 89: 378–390.[CrossRef][Web of Science][Medline]

[6] Jervell A and Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death. Am Heart J 1957; 54: 59–68.[CrossRef][Web of Science][Medline]

[7] Jackman WM, Friday KJ, Anderson JL, Aliot EM, Clark M, Lazzara R. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988; 31: 115–172.[CrossRef][Web of Science][Medline]

[8] Gilmour RF Jr, Riccio ML, Locati EH, Maison-Blanche P, Coumel P, Schwartz PJ. Time- and rate-dependent alterations of the QT interval precede the onset of torsade de pointes in patients with acquired QT prolongation. J Am Coll Cardiol 1997; 30: 209–217.[Abstract]

[9] Viskin S, Alla SR, Barron HV, Heller K, Saxon L, Kitzis I, Hare GF, Wong MJ, Lesh MD, Scheinman MM. Mode of onset of torsade de pointes in the congenital long QT syndrome. J Am Coll Cardiol 1996; 28: 1262–1268.[Abstract]

[10] Schwartz PJ, Zaza A, Locati E, Moss AJ. Stress and sudden death. The case of the long QT syndrome. Circulation 1991; 83:(Suppl II), II71–80.

[11] Rashba EJ, Zareba W, Moss AJ, et al. Influence of pregnancy on the risk for cardiac events in patients with hereditary long QT syndrome? Circulation 1998; 97: 451–456.[Abstract/Free Full Text]

[12] Kappenberger LJ, Gloor HO, Steinbrunn W. A new observation on long QT syndrome. Circulation 1984; 70:(Abstr Suppl II), II251.

[13] Viersma JW, May JF, De Jongste MJ. Long QT syndrome and sudden death during sleep in one family. Eur Heart J 1988; 9:(Abstr Suppl), 45.

[14] Schwartz PJ, Priori SG, Locati EH. 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 1995; 92: 3381–3386.[Abstract/Free Full Text]

[15] Butrous GS and Schwartz PJ. Clinical Aspects of Ventricular Repolarization 1989; London Farrand Press pp. 498.

[16] Merri M, Benhorin J, Alberti M, Locati E, Moss AJ. Electrocardiographic quantitation of ventricular repolarization. Circulation 1989; 80: 1301–1308.[Abstract/Free Full Text]

[17] Stramba-Badiale M, Spagnolo D, Bosi G, Schwartz PJ. Are gender differences in QTc present at birth? Am J Cardiol 1995; 75: 1277–1278.[CrossRef][Web of Science][Medline]

[18] Kunchithapatham S, McDonough E, Joseph N, et al. The QTc does not increase with raised hormone levels during pregnancy. Circulation 1999; 1–581.

[19] Schwartz PJ. The long QT syndrome. In Kulbertus HE and Wellens HJJ (Eds.). Sudden Death 1980; The Hague M Nijhoff pp. 358–378.

[20] Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991; 84: 1136–1144.[Abstract/Free Full Text]

[21] Garson A Jr, Dick M II, Fournier A. The long QT syndrome in children. An international study of 287 patients. Circulation 1993; 87: 1866–1872.[Abstract/Free Full Text]

[22] Malfatto G, Beria G, Sala S, Bonazzi O, Schwartz PJ. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23: 296–301.[Abstract]

[23] De Ambroggi L, Bertoni T, Locati E, Stramba-Badiale M, Schwartz PJ. Mapping of body surface potentials in patients with idiopathic long QT syndrome. Circulation 1986; 74: 1334–1345.[Abstract/Free Full Text]

[24] De Ambroggi L, Negroni MS, Monza E, Bertoni T, Schwartz PJ. Dispersion of ventricular repolarization in the long QT syndrome. Am J Cardiol 1991; 68: 614–620.[CrossRef][Web of Science][Medline]

[25] Han J and Moe GK. Nonuniform recovery of excitability in ventricular muscle. Circ Res 1964; 14: 44–60.[Abstract/Free Full Text]

[26] Kuo CS, Munakata K, Reddy CP, Surawicz B. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential duration. Circulation 1983; 67: 1356–1367.[Abstract/Free Full Text]

[27] Day CP, McComb JM, Campbell RWF. QT dispersion: an indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990; 63: 342–344.[Abstract/Free Full Text]

[28] Priori SG, Napolitano C, Diehl L, Schwartz PJ. Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome. Circulation 1994; 89: 1681–1689.[Abstract/Free Full Text]

[29] Linker NJ, Colonna P, Kekwick CA, Till J, Camm AJ, Ward DE. Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes. Am J Cardiol 1992; 69: 634–638.[CrossRef][Web of Science][Medline]

[30] Mirvis DM. Spatial variation of QT interval in normal persons and patients with acute myocardial infarction. J Am Coll Cardiol 1985; 5: 625–631.[Abstract]

[31] Priori SG, Mortara DW, Napolitano C. Evaluation of the spatial aspects of T-wave complexity in the long-QT syndrome. Circulation 1997; 96: 3006–3012.[Abstract/Free Full Text]

[32] Vincent GM. The heart rate of Romano-Ward syndrome patients. Am Heart J 1986; 112: 61–64.[CrossRef][Web of Science][Medline]

[33] Locati E, Pancaldi A, Pala M, Schwartz PJ. Exercise-induced electrocardiographic changes in patients with the long QT syndrome. Circulation 1988; 78:(Abstr. Suppl II), 42.

[34] Schwartz PJ and Locati E. The idiopathic long QT syndrome. Pathogenetic mechanisms and therapy. Eur Heart J 1985; 6:(Suppl. D), 103–114.

[35] Schwartz PJ, Locati EH, Moss AJ, Crampton RS, Trazzi R, Ruberti U. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome: a worldwide report. Circulation 1991; 84: 503–511.[Abstract/Free Full Text]

[36] Keating MT, Atkinson D, Dunn C, Timothy K, Vincent GM, Leppert M. Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science 1991; 252: 704–706.[Abstract/Free Full Text]

[37] Yiang C, Atkinson D, Towbin JA, et al. Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity. Nature Genetics 1994; 8: 141–147.[CrossRef][Web of Science][Medline]

[38] Towbin JA, Li H, Taggart RT, et al. Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families. Circulation 1994; 90: 2635–2644.[Abstract/Free Full Text]

[39] Schott JJ, Peltier S, Foley P, et al. Mapping of a new gene for the long QT syndrome to chromosome 4q25-27. Am J Hum Genet 1995; 57: 1114–1122.[Web of Science][Medline]

[40] Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995; 80: 805–811.[CrossRef][Web of Science][Medline]

[41] Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia. HERG mutations cause long QT syndrome. Cell 1995; 80: 795–803.[CrossRef][Web of Science][Medline]

[42] Wang Q, Curran ME, Splawski I, et al. Positional cloning of a novel potassium channel gene: KvLQT1 mutations cause cardiac arrhythmias. Nature Genetics 1996; 12: 17–23.[CrossRef][Web of Science][Medline]

[43] Sanguinetti C, Curran ME, Spector PS, Keating MT. Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia. Proc Natl Acad Sci USA 1996; 93: 2208–2212.[Abstract/Free Full Text]

[44] Gellens ME, George AL, George AL Jr, Chen L, et al. Primary structure and functional expression of the human cardiac tetrodotoxin insensitive voltage-dependent sodium channel. Proc Natl Acad Sci USA 1992; 89: 354–358.

[45] Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. KvLQT1 and IsK (minK) proteins associate to form the IKscardiac potassium current. Nature 1996; 384: 78–80.[CrossRef][Medline]

[46] Sanguinetti MC, Curran ME, Zou A, et al. Coassembly of KvLQT1 and minK (IsK) proteins to form cardiac IKspotassium channel. Nature 1996; 384: 80–83.[CrossRef][Medline]

[47] Neyroud N, Tesson F, Denjoy I, et al. A novel mutation in the potassium channel gene KvLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nature Genetics 1997; 15: 186–189.[CrossRef][Web of Science][Medline]

[48] Splawski I, Timothy KW, Vincent GM, Atkinson DL, Keating MT. Molecular basis of the long QT syndrome associated with deafness. N Engl J Med 1997; 336: 1562–1567.[Free Full Text]

[49] Schulze-Bahr E, Wang Q, Wedekind H, et al. KCNE1 mutations cause Jervell and Lange-Nielsen syndrome. Nature Genetics 1997; 17: 267–268.[CrossRef][Web of Science][Medline]

[50] Abbott GW, Sesti F, Splawski I, et al. MiRP1 forms Ikrpotassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999; 97: 175–187.[CrossRef][Web of Science][Medline]

[51] Priori SG, Napolitano C, Ronchetti PHE, et al. Characterization of the prevalence of minK polymorphism and mutations in 140 Long QT syndrome families. Pacing Clin Electrophysiol 1998; 21: 39.

[52] Priori SG, Napolitano C, Schwartz PJ, et al. Mutation in KvLQT1 gene in a patient with cisapride-induced Torsade de Pointes. Eur Heart J 1997; 18: 29.

[53] Russel MW, Dick M II, Collins FS, Brody LC. KvLQT1 mutations in three families with familial or sporadic long QT syndrome. Hum Mol Gen 1996; 9: 1319–1324.

[54] Tanaka T, Nagai R, Tomoike H, et al. Four novel KvLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation 1997; 95: 565–567.[Abstract/Free Full Text]

[55] Priori SG, Napolitano C, Schwartz PJ, et al. Variable phenotype of long QT syndrome patients with the same genetic defect. J Am Coll Cardiol 1998; 31: 349A.

[56] DeJager T, Corbett CH, Badenhorst JCB, Brink PA. Evidence of a long QT gene with varying phenotypic expression in South African families. Mol Genet 1996; 33: 567–573.

[57] Priori SG, Schwartz PJ, Napolitano C, et al. A recessive variant of the Romano-Ward long QT syndrome? Circulation 1998; 97: 2420–2425.[Abstract/Free Full Text]

[58] Roden DM. Taking the ‘Idio’ out of ‘Idiosyncratic’: Predicting Torsades de Pointes. Pacing Clin Electrophysical 1998; 21: 1029–1034.

[59] Priori SG, Diehl L, Schwartz PJ. Torsade de pointes. In Podrid PJ and Kowey PR (Eds.). Cardiac Arrhythmia Mechanisms, Diagnosis and Management 1995; Baltimore Williams & Wilkins pp. 951–963.

[60] Schulze-Bahr E, Haverkamp W, Weibusch H, et al. Frequency and phenotype of HERG mutations in congenital long QT syndrome (LQTS). Circulation 1996; 94: 1–719.[Free Full Text]

[61] Priori SG, Schwartz PJ, Napolitano C, et al. Molecular analysis of HERG -gene in forty-eight unrelated long QT syndrome patients: genotype/phenotype correlation in two families with novel mutations. J Am Coll Cardiol 1997; 29: 184A.

[62] Priori SG, Napolitano C, Schwartz PJ, et al. Identification of novel HERG gene mutations in Long QT syndrome patients. Phenotypic Implications? Pacing Clin Electrophysiol 1997; 20: 1072.[CrossRef]

[63] Benson DW, MacRae CA, Vesley MR, et al. Missense mutation in the pore region of HERG causes familial long QT syndrome. Circulation 1996; 93: 1791–1795.[Abstract/Free Full Text]

[64] Napolitano C, Priori SG, Schwartz PJ, et al. Identification of a mutational hot spot in HERG -related long QT syndrome (LQT2): phenotypic implications. Circulation 1997; 96: 212.

[65] Zhou Z, Gong Q, Priori SG, Napolitano C, January CT. Mechanism of HERG channel dysfunction caused by human Long QT Syndrome mutations in the Cyclic Nucleotide-Binding Domain. Circulation 1999; 100: 1–632.

[66] Bennett PB, Yazawa K, Makita N, George AL, George AL Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature 1995; 376: 683–685.[CrossRef][Medline]

[67] Priori SG, Napolitano C, Brown AM, et al. The loss of function induced by HERG and KvLQT1 mutations does not correlate with the clinical severity of the Long QT Syndrome. Circulation 1998; 98: 1–457.[Abstract/Free Full Text]

[68] Abott GW, Sesti F, Splawski I, et al. MiRP1 forms Ikrpotassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999; 97: 175–187.[CrossRef][Web of Science][Medline]

[69] Bianchi L, Shen Z, Dennis AT, et al. Cellular dysfunction of LQT5-mink mutants: abnormalities of Iks, Ikrand trafficking in long QT syndrome. Hum Mol Genet 1999; 8: 1499–1507.[Abstract/Free Full Text]

[70] Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST-segment elevation in leads V1through V3. A marker for sudden death in patients without demonstrable structural heart disease. Circulation 1998; 97: 457–460.[Abstract/Free Full Text]

[71] Schott JJ, Alshinawi C, Le Marec H, et al. Cardiac conduction defects associated with mutations in SCN5A. Nature Genetics 1999; 25: 20–21.

[72] Brugada P and Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992; 20: 1391–1396.[Abstract]

[73] Chen Q, Kirsch GE, Zhang D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998; 392: 293–295.[CrossRef][Medline]

[74] Alshinawi CR, Veldkamp MW, Van Den Berg MP, et al. A single sodium channel mutation causing both Long QT and Brugada Syndrome. Circulation 1999; 100: 1–494.

[75] Zareba W, Moss AJ, Schwartz PJ, et al. Influence of the genotype on the clinical course of the Long QT Syndrome. N Engl J Med 1998; 339: 960–965.[Abstract/Free Full Text]

[76] Priori SG, Napolitano C, Cantù F, Brown AM, Schwartz PJ. Differential response to Na+channel blockade, ß-adrenergic stimulation, and rapid pacing in a cellular model mimicking the SCN5A and HERG defects present in the long QT syndrome. Circ Res 1996; 78: 1009–1015.[Abstract/Free Full Text]

[77] Schwartz PJ, Moss AJ, Priori SG, et al. Gene-specific influence on the triggers for cardiac arrest in the long QT syndrome. Circulation 1997; 96: 212.

[78] Shimizu W and Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of beta-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and Torsade de Pointes. Circulation 1998; 98: 2314–2322.[Abstract/Free Full Text]

[79] Schwartz PJ, Priori SG, Locati EH, et al. 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 1995; 92: 3381–3386.

[80] Compton SJ, Lux RL, Ramsey MR, et al. Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation 1996; 94: 1018–1022.[Abstract/Free Full Text]

[81] Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the Long-QT syndrome. Clinical impact. Circulation 1999; 99: 529–533.[Abstract/Free Full Text]


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