Effective treatments for FGF12-related early-onset epileptic encephalopathies patients
Effective treatments for FGF12-related early-onset epileptic encephalopathies patients
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FGF12相关早发性癫痫性脑病患者的有效治疗
DOI：
10.1016/j.braindev.2021.04.010
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发表时间：
2021-08-15
影响因子：
1.7
通讯作者：
Mao, Xiao
中科院分区：
文献类型：
--
作者：
Tian, Qi;Li, Haoyu;Mao, Xiao
背景资料：FGF12（FHF 1）基因编码电压门控钠通道（Nav）结合蛋白成纤维细胞生长因子同源因子1（FGF12），可通过调节Nav快速失活的电压依赖性和神经元兴奋性引起癫痫发作。最常见的致病性变体FGF12 c.341G > A相关的早发性癫痫性脑病（EOEE）的特征在于难治性癫痫发作和发育障碍。结果：采用全外显子测序技术，在3名无关的EOEE先证者中鉴定出FGF12的一个新热点变异c.341G > A（NM_021032. 4）。所有先证者在丙戊酸（VPA）和托吡酯（TPM）联合治疗后均无癫痫发作。2例先证者经早期有效治疗后，运动和认知功能均得到改善。为了比较不同治疗策略对该病的有效性，对FGF12相关癫痫的治疗进行了综述。结论：我们报告了3例FGF12 c.341G > A相关EOEE患者，VPA和TPM联合抗癫痫治疗反应良好。本研究首次描述了VPA和TPM联合治疗FGF12 c.341G > A相关EOEE患者。这项研究可能有助于未来对FGF12热点变异的难治性癫痫的药物咨询。(c)2021年日本儿童神经病学学会。Elsevier B.V.出版，保留所有权利。
Background: FGF12 (FHF1) gene encodes voltage-gated sodium channel (Nav)-binding protein fibroblast growth factor homologous factor 1, which could cause seizures by regulating voltage dependence of Nav fast inactivation and neuron excitability. The most common pathogenic variant FGF12 c.341G > A related early-onset epileptic encephalopathies (EOEE) was characterized by intractable seizures and developmental disabilities. Results: Using whole exome sequencing, a de novo hotspot variant c.341G > A (NM_021032.4) of FGF12 was identified in three unrelated EOEE probands. All probands were seizure free after a combination treatment of valproic acid (VPA) and topiramate (TPM). The motor and cognitive skills in two probands were improved due to the early and effective treatment. In order to compare the effectiveness of different treatment strategies for the disease, a review of treatments for FGF12-related epilepsy was made. Conclusion: We reported three FGF12 c.341G > A related EOEE patients responded well to a combination antiepileptic therapy of VPA and TPM. The current study is the first to describe the combination therapy of VPA and TPM in FGF12 c.341G > A related EOEE patients. This study may contribute to future medication consultation for intractable epilepsy with FGF12 hotspot variants. (c) 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.