摘要目的:分析3例KCNMA1基因变异相关神经系统疾病的临床和遗传学特点。方法:对中南大学湘雅医院儿科2020年1月至2022年12月诊治的经临床和基因确诊的3例KCNMA1基因变异相关神经系统疾病患者的资料进行回顾性分析。结果:例1，女，4岁8月龄，因"发作性仰头、低头11个月"就诊，脑电图示背景枕区θ节律，双侧中央、顶、枕、颞区为主尖波、尖慢波散发或阵发，右侧中央、顶、颞区著，予左乙拉西坦抗癫痫发作治疗，发作完全控制。体格检查示构音欠清，身材矮小。患者自幼精神发育迟缓，康复治疗2年后，运动发育正常，语言发育轻度落后。全外显子测序发现KCNMA1基因存在新发c.1807A>G(p.Thr603Ala)突变，评级可能致病(LP)。例2，男，1岁4月龄，因"反复愣神发作6月余"就诊，脑电图监测到近20次癫痫事件，先后予左乙拉西坦、丙戊酸钠及氯硝西泮抗癫痫发作治疗，发作完全控制。颅脑MRI示小脑发育差。发育较正常同龄儿童落后。全外显子测序发现KCNMA1基因存在新发c.756C>A(p.Phe252Leu)突变，评级LP。例3，女，16岁1个月，因"双上肢抖动、言语不清10余年，步态不稳8年"就诊，脑电图未见异常，颅脑MRI示小脑萎缩。发育较正常同龄儿童落后。体格检查：吐词不清，双手抓物不稳，四肢肌力4级，共济失调步态。全外显子测序发现KCNMA1基因存在新发c.1051T>C(p.Ser351Pro)突变，评级LP。结论:KCNMA1基因变异相关神经系统疾病的核心表型包括癫痫、神经发育障碍和阵发性运动障碍，颅脑MRI常见小脑萎缩。

abstractsObjective:To summarize the clinical manifestations and determine the molecular etiology for three KCNMA1-related neurological disorders.Methods:A retrospective clinical data analysis was performed on 3 patients with clinically and genetically diagnosed neurological diseases related to KCNMA1 gene variants who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University from January 2020 to December 2022.Results:Case 1, a 4-year-old and 8-month-old female, was diagnosed with " episodes of head-raising and lowering for 11 months". The electroencephalogram (EEG) showed background theta rhythm in the occipital area, with mainly sharp waves and peaks in the bilateral central, parietal, occipital and temporal areas. Slow waves were scattered or paroxysmal, affecting the central, parietal, and temporal areas on the right side. Levetiracetam was given as an anti-epileptic treatment, and the seizures were completely controlled. Physical examination revealed unclear articulation and short stature. The patient′s mental development has been delayed since childhood. After 2 years of rehabilitation treatment, his motor development was normal and his language development was slightly delayed. Whole-exome sequencing found a novel c. 1807A>G (p.Thr603Ala) mutation in the KCNMA1 gene, which was graded likely pathogenic (LP). Case 2, a male, 1 year and 4 months old, went to the hospital because of " recurrent stupor attacks for more than 6 months". Nearly 20 epileptic events were detected on the electroencephalogram. Levetiracetam, sodium valproate and clonazepam were administered successively. Seizure treatment, complete seizure control. Brain magnetic resonance imaging (MRI) showed poor cerebellar development. Development was lagging behind that of normal children of the same age. Whole-exome sequencing found a novel c. 756C>A (p.Phe252Leu) mutation in the KCNMA1 gene, which was graded LP. Case 3, a 16-month-old female, went to the hospital because of " trembling upper limbs, slurred speech for more than 10 years, and unsteady gait for 8 years." The electroencephalogram showed no abnormalities, and brain MRI showed cerebellar atrophy. Physical examination: unclear speech, unsteady grasping of objects with both hands, muscle strength of limbs level 4, and ataxic gait. Whole-exome sequencing found a novel c. 1051T>C (p.Ser351Pro) mutation in the KCNMA1 gene, which was graded LP.Conclusions:The core phenotypes of KCNMA1 gene mutation-related neurological diseases include epilepsy, neurodevelopmental disorders and paroxysmal dyskinesia, and cerebellar atrophy is common in brain MRI.