肌阵挛-站立不能性癫痫的临床特征及其电压门控性钠通道α1亚基基因突变检测

摘要

目的 探讨肌阵挛-站立不能性癫痫(MAE)的临床特点、药物疗效及可能的分子遗传学机制.方法 根据2001年国际抗癫痫联盟癫痫综合征分类标准对自2006年至2008年在广州医学院第二附属医院神经内科就诊的MAE患者进行诊断,收集患者的临床资料及外周血DNA,采用高效液相色谱分析和直接测序法对电压门控性钠通道α1亚基(5CN1A)基因突变进行筛查,并对其临床治疗情况随访1年以上.结果 共收集10例MAE患者,其中散发8例,有热性惊厥或癫痫家族史者2例;起病年龄介于5～39个月间;有多种全面性发作形式;2例曾出现癫痫持续状态;起病后精神发育迟滞者7例.对其中8例患者进行SCN1A基因突变筛查,均未发现突变.丙戊酸、氯硝安定和左乙拉西坦疗效最好,部分患者托吡酯和拉莫三嗪治疗亦有效.结论 MAE是少见的癫痫综合征,分子遗传学机制不明,丙戊酸、氯硝安定和左乙拉西坦治疗有效,但预后较差.%Objective To study the clinical features and genetic mechanism of myoclonic-astafic epilepsy (MAE) in infancy. Methods This study was conducted among 10 infants with MAE (including 7 male and 3 female patients) diagnosed between 2006 and 2008 according to the criteria of International League Against Epilepsy (2001). The clinical data including onset age, seizure type, physical signs, EEG, brain maguetic resonance imaging (MRI), effects of anti-epileptic drugs and prognosis were analyzed. The mutations of voltage-gated sodium channel subunit type 1 gene (SCN1A gene) were screened by denaturing high performance liquid chromatography and direct sequencing. Results The 10 MAE cases included 8 sporadic cases and 2 with a family history of febrile seizure and epilepsy. The onset age ranged from 5 months to 39 months, and all the MAE patients had multiple generalized seizure types, including myoclonic-atonic, myoclonic, atonic, tonic-clonic and absence seizures. Two patients had myoclonic status epilepticus, and 7 showed mental retardation. All the patients showed normal findings in MRI. SCN1A gene was screened in 8 of the MAE patients, and no mutation was found. Valproate, clonazepam and levetiracetam were effective in these MAE cases. Conclusion MAE is a rare epilepsy syndrome, whose genetic mechanism is still unclear. Valproate, clonazepam and levetiracetam are effective for MAE, which is associated with poor prognosis.