Division of Pediatric Neurology, Epilepsy Research Institute, Severance Children's Hospital, Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Epilepsy Res. 2020 Jul;163:106323. doi: 10.1016/j.eplepsyres.2020.106323. Epub 2020 Mar 27.
Early-onset epileptic encephalopathies with burst suppression (EOEE-BS) are a group of neonatal epileptic syndromes characterized by intractable epilepsy and severe psychomotor delay with structural and metabolic factors accounting for major etiologies. However, recent advances in gene sequencing have identified that genetic factors might also play a significant role in the development of EOEE-BS. Herein, we used various genetic tests to identify pathogenic genetic variants in EOEE-BS irrespective of structural malformations and analyzed the clinical features associated with each different etiology.
A total of 48 patients with EOEE-BS were included. Except for patients with severe hypoxic damage, patients with structural malformations were included in our patient cohort. Clinical features of the patients were reviewed, and etiological diagnoses were made based on several genetic tests, metabolic studies, and radiological findings.
A genetic diagnosis was made in 31 (64.6 %) patients, with the most commonly diagnosed gene being STXBP1 (n = 13, 27.1 %), followed by KCNQ2 (n = 5, 10.4 %), SCN2A (n = 5, 10.4 %), DEPDC5 (n = 3, 6.3 %), CASK (n = 1, 2.1 %), CDKL5 (n = 1, 2.1 %), GNAO1 (n = 1, 2.1 %), SLC6A8 (n = 1, 2.1 %), and LIS1 deletion (n = 1, 2.1 %). Other than the classification of epilepsy syndrome, no clinical features were associated with the genetically diagnosed group. Among eight patients with structural malformations, genetic diagnosis was achieved in five (62.5 %), and those patients had pathogenic mutations in DEPDC5 and CASK or LIS1 deletion, indicating the significance of gene sequencing irrespective of structural abnormalities. Treatment responses to a variety of medications and the ketogenic diet differed by etiology, and surgical resection proved to be effective in patients with cortical dysplasia.
Genetic etiologies are an important factor in EOEE-BS irrespective of structural malformations and the treatment options may differ by etiology.
伴有爆发抑制的早发性癫痫性脑病（EOEE-BS）是一组新生儿癫痫综合征，其特征为难治性癫痫和严重的精神运动发育迟缓，结构性和代谢性因素是主要病因。然而，基因测序的最新进展表明，遗传因素也可能在 EOEE-BS 的发展中起重要作用。在此，我们使用了各种基因检测方法，在不考虑结构畸形的情况下，鉴定 EOEE-BS 的致病性遗传变异，并分析了与每种不同病因相关的临床特征。
共纳入 48 例 EOEE-BS 患者。除了严重缺氧损伤的患者外，我们还将结构畸形患者纳入了研究队列。对患者的临床特征进行了回顾，并基于几种基因检测、代谢研究和影像学发现做出病因诊断。
31 例（64.6%）患者做出了基因诊断，最常见的诊断基因是 STXBP1（n=13，27.1%），其次是 KCNQ2（n=5，10.4%）、SCN2A（n=5，10.4%）、DEPDC5（n=3，6.3%）、CASK（n=1，2.1%）、CDKL5（n=1，2.1%）、GNAO1（n=1，2.1%）、SLC6A8（n=1，2.1%）和 LIS1 缺失（n=1，2.1%）。除了癫痫综合征的分类外，没有其他临床特征与基因诊断组相关。在 8 例结构畸形患者中，有 5 例（62.5%）患者做出了基因诊断，这些患者的 DEPDC5 和 CASK 或 LIS1 缺失存在致病性突变，表明即使没有结构性异常，基因测序也具有重要意义。病因不同，对各种药物和生酮饮食的治疗反应也不同，皮质发育不良患者的手术切除效果较好。
EOEE-BS 的遗传病因是一个重要因素，无论是否存在结构畸形，治疗选择可能因病因而异。
