探讨新生儿结节性硬化症相关性癫痫(TRE)的临床表现、遗传学特点、治疗及转归。

选择2021年8月华中科技大学同济医院收治的1例新生儿期频繁癫痫发作的结节性硬化症(TSC)新生儿(患儿1)为研究对象。回顾性分析其家族史，临床表现，实验室检查与头颅影像学检查结果、分子生物学资料，诊治经过及转归。对国内外新生儿TRE相关研究文献进行复习，总结新生儿TRE临床特点。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。监护人对患儿1的诊治知情同意。

①患儿1为男性，28 d龄，于生后10 d出现抽搐，抽搐持续超过0.5个月后就诊入院。患儿1头颅CT及MRI结果显示，双侧额顶叶皮质下及双侧侧脑室室管膜下多发结节；脑电图监测见局灶性癫痫发作；全外显子组测序结果显示，TSC2基因c.3884-1G>A杂合剪接突变，为疑似致病性突变，来源于其母亲。接受>3种抗癫痫药物(ASM)治疗后，患儿1病情好转，但是癫痫仍然反复发作，发育稍落后于正常同龄儿；于4个月25 d龄时，接受癫痫手术治疗。目前对患儿1随访至11个月龄，未再癫痫发作，发育正常。②文献复习结果：检索到涉及新生儿TRE相关研究文献为18篇，纳入研究的TRE患儿为40例，加上患儿1共计41个家系的41例TRE患儿被纳入本研究。其中，39例患儿的中位发病年龄为生后5 d龄，59.0%首次癫痫发作于生后第1周。这41例患儿中，68.3%首次癫痫发作类型为局灶型发作，66.7%为难治性癫痫；18例(43.9%)接受基因检测中，TSC1基因突变占比16.7%、TSC2基因突变占比72.2%；35例接受随访患儿中，57.1%出现智力发育落后于同性别、同龄儿童。

多数新生儿TRE呈现早发、局灶及难治性特点，对其并发的药物难治性癫痫，可考虑手术治疗。对该病患儿应长期随访，关注有无神经功能损害。

To explore the clinical manifestation, genetic characteristics, treatment and outcome of neonatal tuberous sclerosis complex related epilepsy (TRE).

A newborn(child 1) of tuberous sclerosis complex (TSC) with frequent epileptic seizure in neonatal period admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology in August, 2021 was chosen in this study. Retrospective analysis was made on the family history, clinical manifestation, laboratory results, head imaging and molecular biology data, diagnosis, treatment and prognosis. The clinical features of neonatal TRE were summarized based on literature review of TRE related studies retrieved in domestic and foreign databases. The study followed the requirements of the World Medical Association Declaration of Helsinki revised in 2013. The guardians informed consent to the diagnosis and treatment of the child 1.

① Child 1 was a male newborn and admitted at age of 28 d due to seizure occurred on the 10 d after birth and lasted for more than half month.His cranial CT and MRI showed multiple nodules under the cortex of bilateral frontal parietal lobes and subependymal of bilateral lateral ventricles. Electroencephalogram detected focal seizure. Whole exome sequencing revealed a heterozygous splicing mutation (c.3884-1G>A) in the TSC2 gene of child 1, and it was a suspicious pathogenicity variation originated from his mother. He was improved after antiepileptic treatment of more than 3 kinds of anti-seizure medication (ASM). However, he still had recurrent seizures and was slightly behind normal children of the same age in development. He was treated with surgical treatment of epilepsy at age of 4 months 25 days, and epilepsy was controlled and intelligence was normal followed up to the age of 11 months. ② Literature review results: a total of 18 pieces of literature related to neonatal TRE, including 41 cases from 41 families plus child 1. The median onset age of 39 children was 5 d after birth, and 59.0% had the first seizure in the first week after birth. Among the 41 cases, 68.3% were focal seizures and 66.7% were intractable seizures. 18 cases(43.9%)had accepted gene detection, with TSC1 gene mutations accounting for 16.7% and TSC2 gene mutations accounting for 72.2%. Among 35 cases who were followed up, 57.1% showed mental retardation compare to children of the same gender and age.

Most neonatal TRE was early onset, focal seizure and refractory. Surgical treatment may be helpful to drugs resistant epilepsy. Children with this disease should be followed up for a long time, paying attention to whether there is any neurological system lesion.