发作性过度运动诱发性运动障碍家系报道及突变分析

Analysis of clinical and genetic features of one Chinese family with paroxysmal exercise-induced dyskinesia

目的·探讨发作性过度运动诱发性运动障碍(PED)的临床及遗传学特点,并总结近年该疾病的研究进展。方法·对中国大陆一PED家系进行分析并总结临床特点、药物治疗效果及预后,对家系中5名患者和2名健康家属进行SLC2A1基因检测。进一步对该疾病的临床、遗传学和发病机制的研究进展作一综述。结果·该家系5名患者中包括4名女性和1名男性,其中4人表现为单纯型PED,1人表现为PED合并癫痫。先证者和其女儿服用卡马西平和丙戊酸钠治疗效果不佳。3人随年龄增长呈现发作逐渐减轻的倾向。该家系5名患者均存在突变SLC2A1 c.C284T(p.S95L),2名健康家属不存在该突变。根据ACMG标准和指南,对该突变位点进行致病性预测评估,评级为"致病"。结论·PED是一类罕见的发作性运动障碍,存在一定的临床异质性,并随年龄增长呈现自发缓解的倾向。目前该疾病致病机制未明,总结该病遗传学与发病机制的研究进展可为该病的临床诊断和治疗提供帮助。

Objective · To study the clinical and genetic features of familial paroxysmal exercise-induced dyskinesia （PED） in a Chinese mainland family, and review the advances of clinical and genetic studies on PED. Methods · The clinical information of 7 family members in one Chinese pedigree, including 5 patients and 2 healthy people, was analyzed and the patients’ response to treatment and prediction were followed up. The SLC2A1 gene in all 7 members of this family was sequenced. The clinical and genetic characteristics of 5 patients were analyzed. Advances of recent clinical and genetic studies related with PED were further reviewed. Results · Among the total 5 patients （male ： female=1：4）, four patients had pure form of PED, and one patient had PED plus epilepsy. Attacks of the proband and his daughter could not be well controlled by carbamazepine or sodium valproate. In addition, three patients showed a remission trend with age advancing. In this family, the SLC2A1 c.C284T （p.S95L） was identified in all 5 patients, but not in 2 healthy members. According to the American College of Medical Genetics and Genomics （ACMG） criteria and guideline, the variant SLC2A1 c.C284T （p.S95L） was classified as “pathogenic variant”. Conclusion · PED is a rare paroxysmal movement disorder with highly phenotypic heterogeneity as well as a remission trend with age advancing. This paper reviews advances in clinical and genetic studies on PED recently, in order to contribute to the clinical diagnosis and appropriate treatment of PED.