ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome

Arthur J. Moss, Wojciech Zareba, Jesaia Benhorin, Emanuela H. Locati, W. Jackson Hall, Jennifer L. Robinson, Peter J. Schwartz, Jeffrey Towbin, G. Michael Vincent, Michael H. Lehmann, Mark T. Keating, Jean W. MacCluer, Katherine W. Timothy

Research output: Contribution to journalArticle

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Abstract

Background: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. Methods and Results: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QT(onset-c), QT(peak-c), QT(c) and T(duration-c), in milliseconds) and the absolute height of the T wave (T(amplitude), in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n=47), 7 (n=30), and 11 (n=76). Genotypic data were used to define each family member as being affected or unaffected with long aT syndrome. Affected members of all six families had longer QT intervals (QT(onset-c), QT(peak-c), or QT(c)) than unaffected family members (P<.01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QT(onset-c), was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QT(onset-c) [mean±SD]: chromosome 3, 341±42 ms; chromosome 7, 290±56 ms; chromosome 11, 243±73 ms; P<.001); T(amplitude) was generally quite small in the chromosome 7 genotype (lead II T(amplitude), mV; chromosome 3, 0.36±0.14; chromosome 7, 0.13±0.07; chromosome 11, 0.37±0.17; P<.001); and T(duration) was particularly long in the chromosome 11 genotype (lead II T(duration-e): chromosome 3, 187±33 ms; chromosome 7, 191±51 ms; chromosome 11, 262±65 ms; P<.001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. Conclusions: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

Original languageEnglish (US)
Pages (from-to)2929-2934
Number of pages6
JournalCirculation
Volume92
Issue number10
DOIs
StatePublished - Nov 15 1995

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Long QT Syndrome
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 7
Electrocardiography
Genotype
Genes
Mutation
Genetic Loci
Sodium Channels
Sudden Death
Ion Channels
Tachycardia
Chromosomes
Phenotype

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Moss, A. J., Zareba, W., Benhorin, J., Locati, E. H., Hall, W. J., Robinson, J. L., ... Timothy, K. W. (1995). ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation, 92(10), 2929-2934. https://doi.org/10.1161/01.CIR.92.10.2929

ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. / Moss, Arthur J.; Zareba, Wojciech; Benhorin, Jesaia; Locati, Emanuela H.; Hall, W. Jackson; Robinson, Jennifer L.; Schwartz, Peter J.; Towbin, Jeffrey; Vincent, G. Michael; Lehmann, Michael H.; Keating, Mark T.; MacCluer, Jean W.; Timothy, Katherine W.

In: Circulation, Vol. 92, No. 10, 15.11.1995, p. 2929-2934.

Research output: Contribution to journalArticle

Moss, AJ, Zareba, W, Benhorin, J, Locati, EH, Hall, WJ, Robinson, JL, Schwartz, PJ, Towbin, J, 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, vol. 92, no. 10, pp. 2929-2934. https://doi.org/10.1161/01.CIR.92.10.2929
Moss AJ, Zareba W, Benhorin J, Locati EH, Hall WJ, Robinson JL et al. ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation. 1995 Nov 15;92(10):2929-2934. https://doi.org/10.1161/01.CIR.92.10.2929
Moss, Arthur J. ; Zareba, Wojciech ; Benhorin, Jesaia ; Locati, Emanuela H. ; Hall, W. Jackson ; Robinson, Jennifer L. ; Schwartz, Peter J. ; Towbin, Jeffrey ; Vincent, G. Michael ; Lehmann, Michael H. ; Keating, Mark T. ; MacCluer, Jean W. ; Timothy, Katherine W. / ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. In: Circulation. 1995 ; Vol. 92, No. 10. pp. 2929-2934.
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title = "ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome",
abstract = "Background: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. Methods and Results: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QT(onset-c), QT(peak-c), QT(c) and T(duration-c), in milliseconds) and the absolute height of the T wave (T(amplitude), in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n=47), 7 (n=30), and 11 (n=76). Genotypic data were used to define each family member as being affected or unaffected with long aT syndrome. Affected members of all six families had longer QT intervals (QT(onset-c), QT(peak-c), or QT(c)) than unaffected family members (P<.01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QT(onset-c), was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QT(onset-c) [mean±SD]: chromosome 3, 341±42 ms; chromosome 7, 290±56 ms; chromosome 11, 243±73 ms; P<.001); T(amplitude) was generally quite small in the chromosome 7 genotype (lead II T(amplitude), mV; chromosome 3, 0.36±0.14; chromosome 7, 0.13±0.07; chromosome 11, 0.37±0.17; P<.001); and T(duration) was particularly long in the chromosome 11 genotype (lead II T(duration-e): chromosome 3, 187±33 ms; chromosome 7, 191±51 ms; chromosome 11, 262±65 ms; P<.001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. Conclusions: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.",
author = "Moss, {Arthur J.} and Wojciech Zareba and Jesaia Benhorin and Locati, {Emanuela H.} and Hall, {W. Jackson} and Robinson, {Jennifer L.} and Schwartz, {Peter J.} and Jeffrey Towbin and Vincent, {G. Michael} and Lehmann, {Michael H.} and Keating, {Mark T.} and MacCluer, {Jean W.} and Timothy, {Katherine W.}",
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T1 - ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome

AU - Moss, Arthur J.

AU - Zareba, Wojciech

AU - Benhorin, Jesaia

AU - Locati, Emanuela H.

AU - Hall, W. Jackson

AU - Robinson, Jennifer L.

AU - Schwartz, Peter J.

AU - Towbin, Jeffrey

AU - Vincent, G. Michael

AU - Lehmann, Michael H.

AU - Keating, Mark T.

AU - MacCluer, Jean W.

AU - Timothy, Katherine W.

PY - 1995/11/15

Y1 - 1995/11/15

N2 - Background: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. Methods and Results: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QT(onset-c), QT(peak-c), QT(c) and T(duration-c), in milliseconds) and the absolute height of the T wave (T(amplitude), in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n=47), 7 (n=30), and 11 (n=76). Genotypic data were used to define each family member as being affected or unaffected with long aT syndrome. Affected members of all six families had longer QT intervals (QT(onset-c), QT(peak-c), or QT(c)) than unaffected family members (P<.01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QT(onset-c), was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QT(onset-c) [mean±SD]: chromosome 3, 341±42 ms; chromosome 7, 290±56 ms; chromosome 11, 243±73 ms; P<.001); T(amplitude) was generally quite small in the chromosome 7 genotype (lead II T(amplitude), mV; chromosome 3, 0.36±0.14; chromosome 7, 0.13±0.07; chromosome 11, 0.37±0.17; P<.001); and T(duration) was particularly long in the chromosome 11 genotype (lead II T(duration-e): chromosome 3, 187±33 ms; chromosome 7, 191±51 ms; chromosome 11, 262±65 ms; P<.001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. Conclusions: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

AB - Background: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. Methods and Results: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QT(onset-c), QT(peak-c), QT(c) and T(duration-c), in milliseconds) and the absolute height of the T wave (T(amplitude), in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n=47), 7 (n=30), and 11 (n=76). Genotypic data were used to define each family member as being affected or unaffected with long aT syndrome. Affected members of all six families had longer QT intervals (QT(onset-c), QT(peak-c), or QT(c)) than unaffected family members (P<.01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QT(onset-c), was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QT(onset-c) [mean±SD]: chromosome 3, 341±42 ms; chromosome 7, 290±56 ms; chromosome 11, 243±73 ms; P<.001); T(amplitude) was generally quite small in the chromosome 7 genotype (lead II T(amplitude), mV; chromosome 3, 0.36±0.14; chromosome 7, 0.13±0.07; chromosome 11, 0.37±0.17; P<.001); and T(duration) was particularly long in the chromosome 11 genotype (lead II T(duration-e): chromosome 3, 187±33 ms; chromosome 7, 191±51 ms; chromosome 11, 262±65 ms; P<.001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. Conclusions: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

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