TBC1D24基因突变的早期局灶性肌阵挛癫痫的临床特征和基因突变分析

Clinical features and gene analysis of TBCID24 gene mutation related early-onset focal myoclonicepilepsy

目的分析TBC1D24基因突变的早期局灶性肌阵挛癫痫的临床和基因突变特点。方法回顾性收集2016年11月至2017年6月在首都医科大学宣武医院儿科和神经内科就诊且进行了癫痫相关基因测序的患者，筛选出具有TBClD24基因突变的患者，进而采集病历资料并分析其临床、脑电图及基因突变特点。结果共收集到患者3例，其中男1例、女2例，发作起病年龄分别为4个月、3岁、5岁，2例有癫痫家族史。3例均表现为局灶性肌阵挛发作及持续状态。2例有智力、运动发育落后。3例脑电图监测中均有肌阵挛发作。1例监测到继发四肢阵挛发作，脑电图发作起始部位为左额、左中央。头颅核磁共振成像显示1例双侧小脑异常信号，2例未见异常。基因检测：2例为TBClD24基因复合杂合突变，1例为纯合突变，3例均为新发突变。3例患者均应用多种抗癫痫药治疗，其中2例发作未能有效控制。1例随访10个月，未再发作。结论TBClD24基因突变的早期局灶性肌阵挛癫痫的临床特点为起病年龄早，突出表现为局灶性肌阵挛发作及持续状态，睡眠可缓解，多伴有智力、运动发育落后，对抗癫痫药治疗反应差。发作间期及发作期脑电图多正常。基因检测可协助诊断及指导遗传咨询。

Objective To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutation related early-onset focal myoclonic epilepsy. Methods Clinical data of 3 patients with TBC1 D24 gene mutation related early-onset focal myoclonic epilepsy of Xuanwu Hospital from November 2016 to June 2017 was collected and analyzed. Candidate gene mutations were screened by second generation sequencing. Results Among the 3 patients, 1 was male and 2 were females. Seizure onset age was 4 months, 3 years and 5 years after birth respectively. Two patients had family history of epilepsy. They all had prolonged episodes of focal myoelonus. Two patients had mental retardation. Scalp electroencephalograms （EEG） was recorded in all 3 cases and myoclonie seizures were captured. The ictal EEGs were normal in all cases. In one patient, the ictal EEG of generalized seizure showed alpha rhythm originating from left fronto- central region. Brain magnetic resonance imaging （MRI） was normal in 2 patients. Abnormal signal was found bilaterally in cerebellum in 1 patient. The gene screening showed that two patients carried compound heterozygous mutation of TBC1D24 gene and one carried homozygous mutation, all of which were de novo mutations. All the patients were treated with multiple antiepileptic drugs （AEDs） and seizures were uncontrolled in 2 patients. One patient was followed up for 10 months without recurrence. Conclusions TBC1 D24 gene related early-onset focal myoclonic epilepsy is clinically characterized by early onset ,prolonged focal myoclonus which relieved with sleep, mental retardation and poor response to AEDs. The interictal and ictal EEG usually show normal. Genetic analysis can assist in diagnosis and genetic counseling.