CYFIP2基因变异致发育性癫痫性脑病1例报道

Developmental and epileptic encephalopathy caused by CYFIP2 mutation

目的总结CYFIP2基因变异致发育性癫痫性脑病65型(DEE65)的临床和遗传学特征。方法回顾性分析2019年9月收治于河北省儿童医院神经内科的1例CYFIP2基因变异患儿的临床资料,并进行相关文献复习。结果患儿,女,6岁,因1 d内抽搐发作2次收入院,表现为强直发作;自幼发育落后,2岁10月独走,3岁说话。家系全外显子组基因测序发现患儿CYFIP2基因存在新生杂合突变:c.935A>G(p.Gln312Arg)(NM_001037332)。共检索出国外文献6篇(27例患儿),起病年龄为新生儿至14岁,发作形式多为癫痫性痉挛发作、全面性强直阵挛发作(GTCS)。所有患儿均出现不同程度的发育障碍,常见表型包括形态异常(特殊面容、毛发稀疏、并趾等)、肌张力低下、小头畸形,其他表型包括视力障碍、喂养困难、行为问题、不随意运动等,目前尚无死亡病例。结论CYFIP2基因突变可导致发育性癫痫性脑病、婴儿早期起病、难治性癫痫,发作类型主要为癫痫性痉挛发作,伴不同程度发育障碍,头颅MRI提示不同程度脑萎缩,多数预后差。本例患儿的新生错义突变c.935A>G既往未见报道,扩充了CYFIP2基因突变谱。

Objective To summarize the clinical and genetic characteristics of developmental and epileptic encephalopathy 65 caused by CYFIP2 mutation.Methods The clinical data of a child with CYFIP2 gene mutation admitted in Department of Neurology of Hebei Children's Hospital in September 2019 were retrospectively analyzed and related literatures were reviewed.Results The child,a 6-year-old girl,was admitted to the hospital due to convulsions twice in one day,manifested as generalized tonic seizure.She had developmental delay:walk at two years and ten months,speak at three years.The whole exome gene sequencing revealed a de novo heterozygous mutation in the CYFIP2 gene:c.935A>G(p.Gln312Arg)(NM_001037332).A total of 6 foreign literatures(27 children)were retrieved.The onset age ranged from neonate to 14 years old,and seizure types were mostly epileptic spasm seizures and generalized tonic-clonic seizures(GTCS).All cases presented developmental disabilities of varying degrees.The common phenotypes included morphological abnormalities(special face,sparse hair,syndactyly,etc),hypotonia and microcephaly.Others had Visual impairment,feeding difficulties,behavioral problems,involuntary movement,etc.No deaths have been reported.Conclusion CYFIP2 gene mutation can lead to developmental epileptic encephalopathy,which usually occurs in early infancy and is refractory epilepsy.The most common seizure type is epileptic spasm with different degrees of developmental delay.Brain MRI shows varying degrees of brain trophy.Most cases have poor prognosis.The de novo missense mutation c.935A>G in this child has not been reported before,which expands CYFIP2 gene mutation spectrum.