COL4A1基因突变相关儿童脑病的特征分析:附3例病例报告

Characteristics of mutation in COL4A1 associated with encephalopathy in children:3 cases were reported

目的分析COL4A1基因突变相关儿童脑病的临床症状、影像及遗传学特征。方法回顾性分析安徽省儿童医院于2017年1月至2019年12月收治的3例COL4A1基因突变的患儿临床症状和影像学结果,以"COL4A1""HANAC综合征"等为检索词,在PubMed数据库、中国期刊全文数据库、万方医学以及中国知网文献数据库进行检索,结合文献复习,对COL4A1基因突变引起的儿童脑病的临床症状、影像及遗传学特点进行总结分析。结果1例患儿(11月16天)表现为癫痫发作及生长发育落后,头颅核磁共振(MRI)提示额叶脑穿通畸形和脑室周围白质软化(PVL);1例患儿(2个月14天)仅表现为抽搐,头颅MRI见脑室旁软化灶和脑室周围钙化;1例患儿(3岁)表现为有先天性白内障和生长发育迟缓,头颅MRI考虑脱髓鞘或髓鞘形成不良。3例患儿均有肌酸激酶(CK)的升高。2例是甘氨酸的错义突变,1例发生核苷酸插入,三种均导致肽链中的氨基酸序列发生改变,引起相应的病症。结论COL4A1基因突变具有可变表型的全身性疾病,除了神经系统的表现外,可累及肾、眼、肌肉及皮肤等多系统,CK升高,存在脑室周围钙化或PVL对于该疾病的诊断有指导意义。本病需要尽早发现、及时治疗,对于该家系中无症状的其他成员需进行COL4A1基因筛查,以便进行二级预防和早期干预。

Objective The aim of this study was to analyze the clinical symptoms,imaging and genetic characteristics of mutation in COL4 A1 associated with encephalopathy in children.Methods The clinical symptoms and imaging findings of 3 children with mutation in COL4 A1 admitted in Anhui provincial Children’s Hospital from January 2017 to December 2019 were analyzed retrospectively."COL4 A1"and"Hanac Syndrome"were searched in PubMed database,Chinese Journal full-text database,Wanfang medicine database and Chinese hownet literature database.Moreover,combined with literature review,the clinical symptoms,imaging and genetic characteristics of children with mutation in COL4 A1 associated with encephalopathy were analyzed.Results Among 3 children with mutation in COL4 A1,One case(11 months and 16 days old)presented with epileptic seizures and growth retardation.Head MRI suggested frontal lobe perforation malformation and periventricular white matter softening(PVL).One case(2 months and 14 days old)only presented with convulsions.Head MRI showed paraventricular softening and periventricular calcification.One case(3 years old)presented with congenital cataract and growth retardation,and was considered demyelinating or myelin formation on head MRI.Creatine kinase(CK)was elevated in all 3 cases.Glycine missense mutations in two cases,and nucleotide insertion in one case,which resulted in changes in the amino acid sequence of the peptide chain and caused the corresponding symptoms.Conclusion Mutation in COL4 A1 has a variable phenotype of systemic disease.In addition to the performance of the nervous system,it could involve the kidney,eyes,muscles,skin and other systems.Elevated CK and the presence of periventricular calcification or PVL may be helpful to the diagnosis.The disease requires early detection and treatment.Additional asymptomatic members of the family are screened for the COL4 A1 gene for secondary prevention and early intervention.