目的 总结分析GNAO1基因变异患者的遗传学与临床特征。方法 收集5例GNAO1基因变异患儿的临床资料,回顾性分析其基因变异特点、临床表现及治疗反应。结果 5例GNAO1基因变异患儿,3例为已知变异,2例为新发现的变异;除1例为剪切位点变异,其余4例均为错义突变。2例患儿表现为早发婴儿癫痫性脑病,同时伴有不同程度的运动障碍;3例患儿以锥体外系症状为主要表现（2例表现为肌张力不全,1例表现为手足徐动）,暂无癫痫发作;5例患儿均存在严重的智力运动发育落后。2例癫痫患儿应用多种抗癫痫药物治疗无效;2例主要表现为肌张力不全的患儿,进行了深部脑刺激（DBS）手术治疗,其中1例术后1个月的Burke-Fahn-Marsden肌张力障碍评分（BFMDRS）较术前改善了32.36%,另1例术后改善不明显,术后12个月BFMDRS评分仅降低了7.79%;1例以手足徐动为主要表现的患儿,年龄尚小,预计后期行DBS治疗。结论 GNAO1基因变异患者的临床表型存在异质性,主要表现为发育迟滞、以锥体外系症状为主的运动障碍和/或癫痫发作。该基因变异所致的锥体外系症状以及癫痫发作对药物治疗反应差,DBS可缓解部分患儿的运动障碍。

Objective To investigate the genotypes and phenotypes features of patients with GNAO1 gene variants. Methods Genetic features, clinical manifestations and therapeutic reaction of five patients with GNAO1 gene variants were retrospectively analyzed. Results A total of 5 patients with GNAO1 gene variants were detected, including 4 patients with missense variants and 1 with splice site variation. Three variants were reported previously and two were novel variants. Two children presented with early-onset infantile epileptic encephalopathy with varying degrees of dyskinesia; three children presented with extrapyramidal symptoms (two with dystonia and one with choreoathetosis) and no seizures for the time being; profound developmental delay was observed in all five patients. Two patients with epilepsy did not response to multiple antiepileptic drugs. Two patients with dystonia underwent deep brain stimulation (DBS) therapy. The BFMDRS score decreased by 32.36% one month after surgery in one patient. However, no significant improvement was found in the other patient, and the BFMDRS score decreased by only 7.79% at 12 months postoperatively. One patient with choreoathetosis intended to accept DBS treatment later. Conclusions The majority of GNAO1 gene variants were missense mutation. The clinical manifestations of patients with GNAO1 gene variants were various, mainly presenting with developmental delay, movement disorders, and/or epilepsy. The epilepsy and the extrapyramidal symptoms responded poorly to the medical therapy, and DBS treatment could alleviate the dyskinesia in some patients.