Yang Ying, Niu Xueyang, Cheng Miaomiao, Zeng Qi, Deng Jie, Tian Xiaojuan, Wang Yi, Yu Jing, Shi Wenli, Wu Wenjuan, Ma Jiehui, Li Yufen, Yang Xiaoling, Zhang Xiaoli, Jia Tianming, Yang Zhixian, Liao Jianxiang, Sun Yan, Zheng Hong, Sun Suzhen, Sun Dan, Jiang Yuwu, Zhang Yuehua
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Department of Neurology, Shenzhen Children's Hospital, Shenzhen, China.
Front Mol Neurosci. 2022 Mar 14;15:809163. doi: 10.3389/fnmol.2022.809163. eCollection 2022.
This study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of -related epilepsy and its prognosis and to explore the potential prospects for personalized medicine.
Through a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with -related epilepsy. The three-dimensional protein structure of the variant was modeled to predict the effect of missense variants using PyMOL 2.3 software.
In 35 patients with variants, 22 variants were , and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The proportions of patients with missense variants in the extracellular region and the transmembrane region exhibiting developmental delay were 40% and 63.2%, respectively. The last follow-up age ranged from 11 months to 17 years. Seizures were controlled in 71.4% of patients, and 92% of their seizures were controlled by valproate and/or levetiracetam.
The clinical features of -related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. More than half of the patients had cluster seizures. Phenotypes of -related epilepsy were ranged from mild febrile seizures to severe epileptic encephalopathies. Most patients with variants who experienced seizures had a good prognosis. Valproate and levetiracetam were effective treatments for most patients.
本研究旨在全面了解[相关癫痫]的遗传和表型特征及其预后，并探索个性化医疗的潜在前景。
通过中国的多中心合作，我们分析了[相关癫痫]患者的基因型-表型相关性及抗癫痫药物（ASM）。使用PyMOL 2.3软件对[变异体]的三维蛋白质结构进行建模，以预测[错义变异体]的影响。
在35例携带[变异体]的患者中，22种变异体为[已知变异体]，18种变异体为新发现的。癫痫发作起始年龄从出生后2天至34个月不等（中位年龄：9个月）。22例患者（22/35，62.9%）的癫痫发作起始年龄小于1岁。发作类型包括局灶性发作（68.6%）、全身强直-阵挛发作（60%）、肌阵挛发作（14.3%）和失神发作（11.4%）。其他临床特征包括热敏感型发作（91.4%）、丛集性发作（57.1%）和发育迟缓（45.7%）。2例患者神经影像学检查异常，包括额颞叶皮质发育异常和白质髓鞘发育延迟。12例患者被诊断为热性惊厥附加症，11例为癫痫伴发育迟缓，2例为Dravet综合征，2例为发育性癫痫性脑病，2例为局灶性癫痫，2例为热性惊厥，4例为未分类癫痫。细胞外区域和跨膜区域存在错义变异体且表现出发育迟缓的患者比例分别为40%和63.2%。末次随访年龄范围为11个月至17岁。71.4%的患者癫痫发作得到控制，其中92%的患者癫痫发作通过丙戊酸盐和/或左乙拉西坦得到控制。
[相关癫痫]的临床特征包括通常在婴儿期起病，且发作对热敏感。超过半数患者有丛集性发作。[相关癫痫]的表型范围从轻度热性惊厥到重度癫痫性脑病。大多数携带[变异体]且有发作的患者预后良好。丙戊酸盐和左乙拉西坦对大多数患者是有效的治疗方法。
