Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy

被引:214
作者
Johnson, J. N. [1 ]
Hofman, N. [5 ]
Haglund, C. M. [1 ,2 ]
Cascino, G. D. [3 ]
Wilde, A. A. M. [6 ]
Ackerman, M. J. [1 ,2 ,4 ]
机构
[1] Mayo Clin, Dept Pediat, Div Pediat Cardiol, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Neurol, Div Epilepsy, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN 55905 USA
[5] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
[6] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
关键词
POTASSIUM CHANNEL GENE; CARDIAC-ARRHYTHMIA; ADULT-RAT; MUTATION; EXPRESSION; EVENTS; GLIA; DROSOPHILA; SYMPTOMS; SPECTRUM;
D O I
10.1212/01.wnl.0000335760.02995.ca
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Long QT syndrome (LQTS) typically presents with syncope, seizures, or sudden death. Patients with LQTS have been misdiagnosed with a seizure disorder or epilepsy and treated with antiepileptic drug (AED) medication. The gene, KCNH2, responsible for type 2 LQTS (LQT2), was cloned originally from the hippocampus and encodes a potassium channel active in hippocampal astrocytes. We sought to test the hypothesis that a "seizure phenotype" was ascribed more commonly to patients with LQT2. Methods: Charts were reviewed for 343 consecutive, unrelated patients ( 232 females, average age at diagnosis 27 +/- 18 years, QTc 471 +/- 57 msec) clinically evaluated and genetically tested for LQTS from 1998 to 2006 at two large LQTS referral centers. A positive seizure phenotype was defined as the presence of either a personal or family history of seizures or history of AED therapy. Results: A seizure phenotype was recorded in 98/343 (29%) probands. A seizure phenotype was more common in LQT2 (36/77, 47%) than LQT1 (16/72, 22%, p < 0.002) and LQT3 (7/28, 25%, p < 0.05, NS). LQT1 and LQT3 combined cohorts did not differ significantly from expected, background rates of a seizure phenotype. A personal history of seizures was more common in LQT2 (30/77, 39%) than all other subtypes of LQTS (11/106, 10%, p < 0.001). Conclusions: A diagnostic consideration of epilepsy and treatment with antiepileptic drug medications was more common in patients with LQT2. Like noncardiac organ phenotypes observed in other LQTS-susceptibility genes such as KCNQ1/deafness and SCN5A/gastrointestinal symptoms, this novel LQT2-epilepsy association raises the possibility that LQT2-causing perturbations in the KCNH2-encoded potassium channel may confer susceptibility for recurrent seizure activity. Neurology (R) 2009;72:224-231
引用
收藏
页码:224 / 231
页数:8
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