典型16p11.2缺失综合征的表型及基因型特点  

Clinical phenotype and genetic characteristics of patients with typical 16p11.2 microdeletion syndrome

作　　者：苏惠红 周水珍 李文辉 Su Huihong;Zhou Shuizhen;Li Wenhui(National Children′s Medicial Center,Department of Neurology,Children′s Hospital of Fudan University,Shanghai 201102,China;the Department of Neurology,Children's Hospital of Fudan University at Xiamen,Xiamen 361000,China)

机构地区：[1]国家儿童医学中心、复旦大学附属儿科医院神经科,上海201102 [2]复旦大学附属儿科医院厦门医院神经内科,厦门361000

出　　处：《中华神经科杂志》2023年第9期1018-1026,共9页Chinese Journal of Neurology

摘　　要：目的分析典型16p11.2缺失综合征患儿的临床表型、拷贝数变异、治疗及随访特征。方法回顾性收集2011年8月至2021年12月于复旦大学附属儿科医院神经科诊治的10例典型16p11.2缺失综合征患儿的临床资料,总结其临床表型、拷贝数变异、治疗及随访情况。结果10例患儿中女性4例,男性6例,均伴有癫痫。9例癫痫发病于婴儿期,发病年龄为6.0(4.0,8.5)月龄。4例为局灶性发作(1例首发伴发热),4例为全面性强直阵挛发作,2例为局灶性发作合并全面性强直阵挛发作;8例为丛集性发作(24 h内发作2至10余次),1例曾发生1次癫痫持续状态。9例患儿在癫痫发病时未提示明显发育迟缓,1例在14月龄癫痫发病时伴有发育迟缓。1例患儿合并左足并趾,1例合并大头畸形且四肢肌张力低。基因检测发现,10例患儿携带典型16p11.2杂合缺失,缺失片段的起始位置为Chr16:29478119-29675016,结束位置为Chr16:30125670-30206112,缺失长度525~712 kb,均考虑为致病性变异。在抗癫痫药物治疗中,4例患儿应用奥卡西平,2例应用丙戊酸钠,2例左乙拉西坦无效后换用奥卡西平,1例应用左乙拉西坦联合丙戊酸钠,1例应用左乙拉西坦先后联合丙戊酸钠、生酮饮食,现10例患儿均无癫痫发作。1例在学龄期出现发作性运动诱发性运动障碍,应用奥卡西平治疗后发作减少。对10例患儿进行随访发现,有9例患儿存在不同程度的发育迟缓(语言受累显著),其中3例合并孤独症样表现,1例入常规小学后家长发现患儿理解能力差,学习困难,多次留级。结论典型16p11.2缺失综合征存在16p11.2近端区域上的基因片段缺失,表现为婴儿期起病的药物反应性丛集性癫痫发作,可伴有语言发育迟缓、孤独症谱系障碍及非特异性畸形。Objective To analyze the clinical phenotype,copy number variation,treatment and follow-up characteristics of children with typical 16p11.2 deletion syndrome.Methods The clinical data of 10 children with typical 16p11.2 deletion syndrome who were treated in the Department of Neurology,Children′s Hospital of Fudan University from August 2011 to December 2021 were retrospectively collected,and their clinical phenotype,copy number variation,treatment and follow-up were summarized.Results Among the 10 children,4 are female and 6 are male,all with epilepsy.Nine patients had epilepsy in infancy,and the age of onset was 6.0(4.0,8.5)months.Four cases had focal seizures(1 with fever),4 had generalized tonic-clonic seizures,and 2 had focal seizures with generalized tonic-clonic seizures.Eight cases had cluster seizures(more than 2 to 10 seizures within 24 hours),and 1 case had 1 status epilepticus.Nine children did not show obvious developmental delay at the onset of epilepsy,and 1 child had developmental delay at the onset of epilepsy at 14 months of age.One child had parallel toes at left foot,and 1 had macrocephaly and low limb muscle tone.Genetic testing found that 10 children carried typical 16p11.2 heterozygous deletion,the starting position of the deletion fragment was Chr16:29478119-29675016,the ending position was Chr16:30125670-30206112,and the deletion length was 525-712 kb,all of which were considered pathogenic variants.In the antiepileptic drug treatment,4 children were treated with oxcarbazepine,2 with sodium valproate,2 was switched to oxcarbazepine after levetiracetam was ineffective,1 with levetiracetam combined with sodium valproate,and 1 with levetiracetam in combination with sodium valproate and ketogenic diet,and all 10 children had no seizures.One patient developed episodic exercise-induced dyskinesia at school age,and the seizures decreased after treatment with oxcarbazepine.Follow-up of 10 children found that 9 children had different degrees of developmental delay(language was significantly affect

关 键 词：典型16p11.2缺失 癫痫 发作性运动诱发性运动障碍 语言发育迟缓 孤独症 

分 类 号：R742.1[医药卫生—神经病学与精神病学]