Chung Chi-Ting, Lee Ni-Chung, Lin I-Ting, Chen Pin-Yu, Jao Tun
Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan.
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Epileptic Disord. 2024 Dec;26(6):814-826. doi: 10.1002/epd2.20286. Epub 2024 Sep 16.
Genetic causes are often overlooked in patients with epilepsy of unknown etiology, particularly in adults. We aimed to evaluate clinical features of genetic epilepsy and the utility of genetic testing.
We retrospectively screened consecutive unrelated adult epilepsy patients at an epilepsy clinic from April 2022 to May 2023. Patients with unknown etiology or special brain lesions were classified as unexplained epilepsy. In them, patients with young-onset seizures or family history of seizures who were recommended for and ultimately underwent genetic testing using either panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were enrolled. A definite or probable genetic diagnosis was established through genotype-phenotype correlation. We compared the demographic characteristics between genetic epilepsy and other etiologies.
Of the 374 adult epilepsy patients, 258 were classified as unexplained epilepsy, 129 were suspected of having genetic epilepsy due to young-onset seizures or a positive family history, 33 underwent genetic testing; 13 harbored variants classified as pathogenic, and 6 reached a definite genetic diagnosis, resulting in a yield of 18%. Among the 27 patients without a definite genetic diagnosis, 7 had a nongenetic structural etiology. Patients with genetic etiology exhibited greater multisystem involvement particularly multiple structural anomalies and early childhood-onset seizures, but wasn't directly correlated with young-onset seizures or a positive family history. The diagnostic yield was comparable between panel NGS and WES.
In adult patients with unexplained epilepsy, genetic epilepsy is more associated with multisystem involvement and multiple structural anomalies but not family history of seizures or young-onset seizures.
在病因不明的癫痫患者中，遗传因素常常被忽视，尤其是在成人患者中。我们旨在评估遗传性癫痫的临床特征以及基因检测的效用。
我们回顾性筛查了2022年4月至2023年5月在一家癫痫诊所连续就诊的无亲属关系的成年癫痫患者。病因不明或有特殊脑损伤的患者被归类为不明原因癫痫。在这些患者中，纳入了因早发性癫痫发作或有癫痫家族史而被推荐并最终接受了基因检测的患者，检测方法为基因panel二代测序（NGS）或全外显子测序（WES）。通过基因型-表型相关性建立明确或可能的基因诊断。我们比较了遗传性癫痫与其他病因之间的人口统计学特征。
在374例成年癫痫患者中，258例被归类为不明原因癫痫，129例因早发性癫痫发作或家族史阳性而疑似患有遗传性癫痫，33例接受了基因检测；13例携带被分类为致病性的变异，6例达成明确的基因诊断，诊断率为18%。在27例未达成明确基因诊断的患者中，7例有非遗传结构性病因。有遗传病因的患者表现出更多的多系统受累，特别是多发结构性异常和儿童早期癫痫发作，但与早发性癫痫发作或家族史阳性无直接关联。基因panel NGS和WES的诊断率相当。
在病因不明的成年癫痫患者中，遗传性癫痫与多系统受累和多发结构性异常的关联更大，但与癫痫家族史或早发性癫痫发作无关。
