Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations.
BACKGROUND
Congenital long QT syndrome (LQTS) is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients (91%) have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China.


METHODS
Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing.


RESULTS
Three of 16 LQTS patients (18.7%) were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was (17 ± 3) years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was (515 ± 17) ms, similar to those with single mutation or SNPs ((536 ± 74) ms, P = 0.63). Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event (P = 0.03 and 0.001, respectively), but lower percentage of them presented with sudden cardiac death (P = 0.03).


CONCLUSIONS
Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients (18.7%, 95% confidence interval: 0.04-0.46) with bigenic mutations in Taiwan. However, the severity of their clinical presentations was not higher than those patients with single mutation or SNPs.
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Juang Jyh-Ming
JJ
Jimmy
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Ching-Yu
CY
Chen
Department of Anesthesiology, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Huei-Ming
HM
Yeh
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Wei-Yih
WY
Chiu
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Chih-Chieh
CC
Yu
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Yen-Bin
YB
Liu
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Chia-Ti
CT
Tsai
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, and Cardiovascular Research Institute, Yang-Ming University, Taipei, China.
Li-Wei
LW
Lo
Department of Environmental and Occupational Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China.
Shih-Fan Sherri
SF
Yeh
Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan, China. Email: lplai2003@ntu.edu.tw.
Ling-Ping
LP
Lai
D000293:Adolescent; D000328:Adult; D000368:Aged; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D055815:Young Adult
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human