Ko Ara, Youn Song Ee, Kim Se Hee, Lee Joon Soo, Kim Sangwoo, Choi Jong Rak, Kim Heung Dong, Lee Seung-Tae, Kang Hoon-Chul
Division of Pediatric Neurology, Epilepsy Research Institute, Severance Children's Hospital, Department of Pediatrics, Yonsei University College of Medicine, 03722 Yonsei-ro 50-1, Seodaemun-gu, Seoul, Republic of Korea.
Severance Biomedical Science Institute, Yonsei University College of Medicine, 03722 Yonsei-ro 50-1, Seodaemun-gu, Seoul, Republic of Korea.
Epilepsy Res. 2018 Mar;141:48-55. doi: 10.1016/j.eplepsyres.2018.02.003. Epub 2018 Feb 12.
We performed targeted gene-panel sequencing for children with developmental and epileptic encephalopathy (DEE) and evaluated the clinical implications of genotype-phenotype correlations.
We assessed 278 children with DEE using a customized gene panel that included 172 genes, and extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype.
In 103 (37.1%) of the 278 patients with DEE, 35 different disease-causing monogenic mutations were identified. The diagnostic yield was higher among patients who were younger at seizure onset, especially those whose seizures started during the neonatal period, and in patients with drug-resistant epilepsy. According to epilepsy syndromes, the diagnostic yield was the highest among patients with West syndrome (WS) with a history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most frequently identified. On the basis of genotypes, we evaluated the clinical progression and seizure outcomes with specific therapeutic regimens; these were similar to those reported previously. In particular, sodium channel blockers were effective in patients with mutations in KCNQ2 and SCN2A in infancy, as well as SCN8A, and interestingly, the ketogenic diet also showed diverse efficacy for patients with SCN1A, CDKL5, KCNQ2, STXBP1, and SCN2A mutations. Unfortunately, quinidine was not effective in 2 patients with migrating focal epilepsy in infancy related to KCNT1 mutations.
Targeted gene-panel sequencing is a useful diagnostic tool for DEE in children, and genotype-phenotype correlations are helpful in anticipating the clinical progression and treatment efficacy among these patients.
我们对发育性和癫痫性脑病（DEE）患儿进行了靶向基因panel测序，并评估了基因型-表型相关性的临床意义。
我们使用包含172个基因的定制基因panel评估了278例DEE患儿，并根据基因型广泛回顾了他们的临床特征，包括治疗效果。
在278例DEE患者中的103例（37.1%）中，鉴定出35种不同的致病单基因变异。癫痫发作起始年龄较小的患者，尤其是那些在新生儿期开始发作的患者以及耐药性癫痫患者的诊断率更高。根据癫痫综合征，在有新生儿发作史的West综合征（WS）患者中诊断率最高，最常鉴定出KCNQ2和STXBP1的突变。基于基因型，我们评估了特定治疗方案的临床进展和癫痫发作结局；这些与先前报道的相似。特别是，钠通道阻滞剂对婴儿期KCNQ2、SCN2A以及SCN8A突变的患者有效，有趣的是，生酮饮食对SCN1A、CDKL5、KCNQ2、STXBP1和SCN2A突变的患者也显示出不同的疗效。不幸的是，奎尼丁对2例与KCNT1突变相关的婴儿期游走性局灶性癫痫患者无效。
靶向基因panel测序是儿童DEE的一种有用诊断工具，基因型-表型相关性有助于预测这些患者的临床进展和治疗效果。
