KCNMA1基因新生突变致阵发性非运动源性运动障碍伴发育落后3例  

De novo KCNMA1 mutations in 3 children with paroxysmal nonkinesigenic dyskinesia and developmental delay

作　　者：田茂强[1,2] 张仲斌[1] 高凯[1] 班婷婷[1] 姜玉武[1] 吴晔[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]遵义医学院附属医院儿科,563003

出　　处：《中华实用儿科临床杂志》2017年第12期916-919,共4页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的分析3例KCNMA1基因新生突变致阵发性非运动源性运动障碍伴发育落后患儿的临床特点，丰富目前已知的KCNMA1突变临床表型。方法收集患儿临床资料，包括性别、年龄、围生期情况、个人史、家族史等一般资料；收集患儿临床表型信息，包括发作特征、发育里程碑、体格检查、治疗药物及治疗反应等；收集临床辅助检查资料，包括血常规生化、代谢筛查结果，基因检测及家系验证结果，并进行临床表型分析和基因型分析。结果1．临床表型特点：3例均为男童。起病年龄：分别为20d、7个月及13个月；3例患儿均为非运动源性运动障碍，表现为突然出现肢体或躯干肌张力不全姿势，有时伴斜视或眼球震颤；或表现为主动运动突然减少、肌张力减低，发作期意识清楚，发作前无明确诱因；发育里程碑均不同程度落后；3例患儿确诊前均使用过多种抗癫痫药物治疗无效，确诊后2例使用氯硝西泮治疗，1例发作明显减少；末次随访时年龄分别为3岁6个月、7岁及5岁8个月，均无癫痫发作，运动障碍发作频率均较前减少；辅助检查：脑电图无异常；头颅磁共振成像未见异常；血尿代谢筛查（-）；脑脊液葡萄糖、叶酸正常。2．基因型：3例均检测到KCNMA1基因杂合错义突变，1例为c．2650G〉A（P．Glu884Lys），2例为c．3158A〉G（P．Asn1053Ser），父母均未检测到该突变。结论此发现丰富了KCNMA1突变患者的临床表型，对于早发阵发性非运动源性运动障碍、发育落后、伴或不伴癫痫的患者，KCNMA1基因应作为候选基因进行筛查。Objective To analyze the clinical characteristics of 3 unrelated boys with paroxysmal nonkinesigenic dyskinesia and developmental delay caused by de novo mutation in KCNMA1, and to expand the knowledge of clinical phenotype of KCNMA1 mutation. Methods Clinical data of patients were collected, including gender, age, condition of the perinatal period, personal history, and family history. And the features of genotype data were collected including features of attack,developmental milestones,physical examinations, treatments, and responses to treatment. The data including blood biochemical results, results of metabolic screening and genetic testing and the pedigree validation were collected, while the relationship between phenotype and genotypc was analyzed. Results （ 1 ） Phenotypic features ： 3 unrelated boys were diagnosed. The ages of disease onset were 20 days ,7 months and 13 months ,respectively. All the patients manifested paroxysmal nonkinesigenic dyskinesia and were characterized by the episodes that occurred during wakefulness,presented with sudden onset of asymmetric limb dystonic posture, sometimes with nystagmus and strabis- mus, or sudden decrease of voluntary movement of limbs with hypotonia and occasional esotropia and yawning. There was no loss of awareness during attack. No precipitating factors were observed before attacks. The developmental milestones were delayed. Three children had no response to anti-epilepsy drug before diagnosis. After diagnosis ,2 cases used Clonazepam and 1 case showed less attack. There was not any epileptic seizure until the last follow - up at the ages of 3 years and 6 months old, 7 years old, and 5 years and 8 months old, respectively. The frequency of attacks was decreased. The episodes were recorded during video - electroencephalogram（EEG） monitoring,which showed normal ictal and interictal EEG. （2） Genotypic featm＇es ： all 3 children were detected to have KCNMA1 genetic heterozygous missense mutation,while c. 2650G 〉 A （p. Glu884Lys） mutation

关 键 词：阵发性非运动源性运动障碍 发育落后 癫痫 KCNMA1基因 

分 类 号：R748[医药卫生—神经病学与精神病学]