Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: Characteristic T-U-wave patterns predict the KCNJ2 genotype

Li Zhang, D. Woodrow Benson, Martin Tristani-Firouzi, Louis J. Ptacek, Rabi Tawil, Peter J. Schwartz, Alfred L. George, Minoru Horie, Gregor Andelfinger, Gregory L. Snow, Ying Hui Fu, Michael John Ackerman, G. Michael Vincent

Research output: Contribution to journalArticle

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Abstract

Background - The ECG features of Andersen-Tawil syndrome (ATS) patients with KCNJ2 mutations (ATS1) have not been systematically assessed. This study aimed to define ECG features of KCNJ2 mutation carriers, to determine whether characteristic T-U-wave patterns exist, and to establish whether T-U patterns predict the ATS1 genotype. Methods and Results - In phase I, evaluation of T-U morphology in ECGs of 39 KCNJ2 mutation carriers identified characteristic T-U patterns: prolonged terminal T downslope, wide T-U junction, and biphasic and enlarged U waves. In phase II, ATS1 genotype prediction by T-U pattern was evaluated in the next 147 ECGs (57 other KCNJ2 mutation carriers, 61 unaffected family members, and 29 ATS patients without KCNJ2 mutations), with a sensitivity of 84% and specificity of 97%. Characteristic T-U patterns were present in 91% (87/96), in whom an enlarged U wave was predominant (73%). In phase III, QTc, QUc, and T- and U-wave duration/amplitude were compared in the 96 ATS1, 29 non-KCNJ2 ATS, and 75 normal subjects. In ATS1 patients, QUc, U-wave duration and amplitude, and QTc were all increased (P<0.001), but median QTc and interquartile range (IQR) were just 440 ms (IQR, 28 ms) compared with 420 ms (IQR, 20 ms) in normal subjects and 425 ms (IQR, 48 ms) in ATS non-KCNJ2 patients. Conclusions - In ATS1 patients, gene-specific T-U-wave patterns resulting from decreased IK1 owing to KCNJ2 mutations can aid diagnosis and direct genotyping. The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7.

Original languageEnglish (US)
Pages (from-to)2720-2726
Number of pages7
JournalCirculation
Volume111
Issue number21
DOIs
StatePublished - May 31 2005

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Andersen Syndrome
Genotype
Electrocardiography
Mutation
Long QT Syndrome
Sensitivity and Specificity

Keywords

  • Arrhythmia
  • Electrocardiography
  • Genetics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zhang, L., Benson, D. W., Tristani-Firouzi, M., Ptacek, L. J., Tawil, R., Schwartz, P. J., ... Vincent, G. M. (2005). Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: Characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation, 111(21), 2720-2726. https://doi.org/10.1161/CIRCULATIONAHA.104.472498

Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations : Characteristic T-U-wave patterns predict the KCNJ2 genotype. / Zhang, Li; Benson, D. Woodrow; Tristani-Firouzi, Martin; Ptacek, Louis J.; Tawil, Rabi; Schwartz, Peter J.; George, Alfred L.; Horie, Minoru; Andelfinger, Gregor; Snow, Gregory L.; Fu, Ying Hui; Ackerman, Michael John; Vincent, G. Michael.

In: Circulation, Vol. 111, No. 21, 31.05.2005, p. 2720-2726.

Research output: Contribution to journalArticle

Zhang, L, Benson, DW, Tristani-Firouzi, M, Ptacek, LJ, Tawil, R, Schwartz, PJ, George, AL, Horie, M, Andelfinger, G, Snow, GL, Fu, YH, Ackerman, MJ & Vincent, GM 2005, 'Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: Characteristic T-U-wave patterns predict the KCNJ2 genotype', Circulation, vol. 111, no. 21, pp. 2720-2726. https://doi.org/10.1161/CIRCULATIONAHA.104.472498
Zhang, Li ; Benson, D. Woodrow ; Tristani-Firouzi, Martin ; Ptacek, Louis J. ; Tawil, Rabi ; Schwartz, Peter J. ; George, Alfred L. ; Horie, Minoru ; Andelfinger, Gregor ; Snow, Gregory L. ; Fu, Ying Hui ; Ackerman, Michael John ; Vincent, G. Michael. / Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations : Characteristic T-U-wave patterns predict the KCNJ2 genotype. In: Circulation. 2005 ; Vol. 111, No. 21. pp. 2720-2726.
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abstract = "Background - The ECG features of Andersen-Tawil syndrome (ATS) patients with KCNJ2 mutations (ATS1) have not been systematically assessed. This study aimed to define ECG features of KCNJ2 mutation carriers, to determine whether characteristic T-U-wave patterns exist, and to establish whether T-U patterns predict the ATS1 genotype. Methods and Results - In phase I, evaluation of T-U morphology in ECGs of 39 KCNJ2 mutation carriers identified characteristic T-U patterns: prolonged terminal T downslope, wide T-U junction, and biphasic and enlarged U waves. In phase II, ATS1 genotype prediction by T-U pattern was evaluated in the next 147 ECGs (57 other KCNJ2 mutation carriers, 61 unaffected family members, and 29 ATS patients without KCNJ2 mutations), with a sensitivity of 84{\%} and specificity of 97{\%}. Characteristic T-U patterns were present in 91{\%} (87/96), in whom an enlarged U wave was predominant (73{\%}). In phase III, QTc, QUc, and T- and U-wave duration/amplitude were compared in the 96 ATS1, 29 non-KCNJ2 ATS, and 75 normal subjects. In ATS1 patients, QUc, U-wave duration and amplitude, and QTc were all increased (P<0.001), but median QTc and interquartile range (IQR) were just 440 ms (IQR, 28 ms) compared with 420 ms (IQR, 20 ms) in normal subjects and 425 ms (IQR, 48 ms) in ATS non-KCNJ2 patients. Conclusions - In ATS1 patients, gene-specific T-U-wave patterns resulting from decreased IK1 owing to KCNJ2 mutations can aid diagnosis and direct genotyping. The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7.",
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AU - Benson, D. Woodrow

AU - Tristani-Firouzi, Martin

AU - Ptacek, Louis J.

AU - Tawil, Rabi

AU - Schwartz, Peter J.

AU - George, Alfred L.

AU - Horie, Minoru

AU - Andelfinger, Gregor

AU - Snow, Gregory L.

AU - Fu, Ying Hui

AU - Ackerman, Michael John

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N2 - Background - The ECG features of Andersen-Tawil syndrome (ATS) patients with KCNJ2 mutations (ATS1) have not been systematically assessed. This study aimed to define ECG features of KCNJ2 mutation carriers, to determine whether characteristic T-U-wave patterns exist, and to establish whether T-U patterns predict the ATS1 genotype. Methods and Results - In phase I, evaluation of T-U morphology in ECGs of 39 KCNJ2 mutation carriers identified characteristic T-U patterns: prolonged terminal T downslope, wide T-U junction, and biphasic and enlarged U waves. In phase II, ATS1 genotype prediction by T-U pattern was evaluated in the next 147 ECGs (57 other KCNJ2 mutation carriers, 61 unaffected family members, and 29 ATS patients without KCNJ2 mutations), with a sensitivity of 84% and specificity of 97%. Characteristic T-U patterns were present in 91% (87/96), in whom an enlarged U wave was predominant (73%). In phase III, QTc, QUc, and T- and U-wave duration/amplitude were compared in the 96 ATS1, 29 non-KCNJ2 ATS, and 75 normal subjects. In ATS1 patients, QUc, U-wave duration and amplitude, and QTc were all increased (P<0.001), but median QTc and interquartile range (IQR) were just 440 ms (IQR, 28 ms) compared with 420 ms (IQR, 20 ms) in normal subjects and 425 ms (IQR, 48 ms) in ATS non-KCNJ2 patients. Conclusions - In ATS1 patients, gene-specific T-U-wave patterns resulting from decreased IK1 owing to KCNJ2 mutations can aid diagnosis and direct genotyping. The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7.

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