Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation

被引：212

作者：

Kato, Mitsuhiro ^{[1
]}

Yamagata, Takanori ^{[2
]}

Kubota, Masaya ^{[3
]}

Arai, Hiroshi ^{[4
]}

Yamashita, Sumimasa ^{[5
]}

Nakagawa, Taku ^{[6
]}

Fujii, Takanari ^{[7
]}

Sugai, Kenji ^{[8
]}

Imai, Kaoru ^{[9
]}

Uster, Tami ^{[10
]}

Chitayat, David ^{[10
,11
]}

Weiss, Shelly ^{[12
]}

Kashii, Hirofumi ^{[3
]}

Kusano, Ryosuke ^{[2
]}

Matsumoto, Ayumi ^{[2
]}

Nakamura, Kazuyuki ^{[1
,13
]}

Oyazato, Yoshinobu ^{[6
]}

Maeno, Mari ^{[6
]}

Nishiyama, Kiyomi ^{[13
]}

Kodera, Hirofumi ^{[13
]}

Nakashima, Mitsuko ^{[13
]}

Tsurusaki, Yoshinori ^{[13
]}

Miyake, Noriko ^{[13
]}

Saito, Kayoko ^{[14
]}

Hayasaka, Kiyoshi ^{[1
]}

Matsumoto, Naomichi ^{[13
]}

Saitsu, Hirotomo ^{[13
]}

机构：

[1] Yamagata Univ, Fac Med, Dept Pediat, Yamagata 9909585, Japan

[2] Jichi Med Univ, Dept Pediat, Shimotsuke, Tochigi, Japan

[3] Natl Ctr Child Hlth & Dev, Div Neurol, Tokyo, Japan

[4] Morinomiya Hosp, Dept Pediat Neurol, Osaka, Japan

[5] Kanagawa Childrens Med Ctr, Div Child Neurol, Yokohama, Kanagawa, Japan

[6] Kobe Univ, Grad Sch Med, Dept Pediat, Kobe, Hyogo 657, Japan

[7] Showa Univ, Fac Med, Dept Pediat, Tokyo, Japan

[8] Natl Ctr Neurol & Psychiat, Natl Ctr Hosp, Dept Child Neurol, Tokyo, Japan

[9] Tokyo Womens Med Univ, Dept Pediat, Tokyo, Japan

[10] Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON M5G 1X5, Canada

[11] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada

[12] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Neurol, Toronto, ON M5G 1X8, Canada

[13] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 232, Japan

[14] Tokyo Womens Med Univ, Inst Med Genet, Tokyo, Japan

来源：

EPILEPSIA | 2013年 / 54卷 / 07期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

KCNQ2; Ohtahara syndrome; Early onset epileptic encephalopathy; Mosaic; Ion channel; FAMILIAL NEONATAL CONVULSIONS; DE-NOVO MUTATIONS; MENTAL-RETARDATION; OHTAHARA-SYNDROME; MYOCLONIC EPILEPSY; SEQUENCING DATA; CHANNEL GENE; BENIGN; EXPANSION; SEIZURES;

D O I：

10.1111/epi.12200

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Purpose: KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation. Methods: A total of 239 patients with EOEE, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high-resolution melting (HRM) analysis or whole-exome sequencing. Detailed clinical information including electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were collected from patients with KCNQ2 mutation. Key Findings: A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression-burst pattern on EEG was found in most. Only three patients showed hypsarrhythmia on EEG; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate-to-profound intellectual disability was found in all except one patient who died at 3 months. Significance: De novo KCNQ2 mutations are involved in EOEE, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression-burst EEG pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for KCNQ2 should be considered for patients with EOEE.

引用

页码：1282 / 1287

页数：6

共 25 条

[1]

A potassium channel mutation in neonatal human epilepsy [J].