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(Circulation. 2005;111:2720-2726.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations

Characteristic T-U–Wave Patterns Predict the KCNJ2 Genotype

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

From the LDS Hospital, Salt Lake City, Utah (L.Z., G.S., G.M.V.); Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (D.W.B., G.A.); University of Utah, Salt Lake City (L.Z., M.T.F., G.M.V.); Howard Hughes Medical Institute, University of California, San Francisco (L.J.P., Y.H.F.); University of Rochester School of Medicine and Dentistry, Rochester, NY (R.T.); University of Pavia and Policlinico S. Matteo, IRCCS, Pavia, Italy (P.J.S.); Vanderbilt University School of Medicine, Nashville, Tenn (A.L.G.); Shiga University of Medical Science, Seta-Tsukinowa, Japan (M.H.); and Mayo Clinic College of Medicine (M.J.A.), Rochester, Minn.

Correspondence to G. Michael Vincent, MD, Department of Medicine, LDS Hospital, 324 10th Ave, Suite 130, Salt Lake City, Utah 84103. E-mail ldgvince{at}ihc.com

Received May 4, 2004; revision received January 11, 2005; accepted January 20, 2005.

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 I_K1 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.

Key Words: arrhythmia • electrocardiography • genetics

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