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


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.
Zhang
Li
L
LDS Hospital, 324 10th Ave, Suite 130, Salt Lake City, Utah 84103, USA.
Benson
D Woodrow
DW
Tristani-Firouzi
Martin
M
Ptacek
Louis J
LJ
Tawil
Rabi
R
Schwartz
Peter J
PJ
George
Alfred L
AL
Horie
Minoru
M
Andelfinger
Gregor
G
Snow
Gregory L
GL
Fu
Ying-Hui
YH
Ackerman
Michael J
MJ
Vincent
G Michael
GM
D000328:Adult; D050030:Andersen Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003937:Diagnosis, Differential; D004562:Electrocardiography; D005192:Family Health; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011237:Predictive Value of Tests
C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying