目的 探讨伴有痉挛性双瘫和视觉缺陷的神经发育障碍(NEDSDV)患儿的临床特征和基因变异特点。方法 回顾性分析2014—2020年在南京市儿童医院康复科确诊的5例NEDSDV患儿的临床表现、实验室检查及基因检测结果,结合文献复习总结NEDSDV患儿的临床及基因特点。结果 5例患儿均表现出全面性发育迟缓、小头畸形、痉挛性双瘫特征,其中例1、例2、例3、例5均有斜视,例5有严重的先天性视网膜渗出性病变。基因检测鉴定5例患儿均为新发的CTNNB1基因杂合变异,且均为截短变异（包括无义和移码变异）,其中c.478_479insTAAATGA、c.1973dupT和c.625G>T为新发现的变异。除1例患儿胼胝体压部略薄外余4例患儿均未见显著的脑影像学异常,而视网膜病变亦相对少见。结论 全面性发育迟缓伴有小头畸形和痉挛性双瘫可作为疑诊NEDSDV的指征,而眼病变及脑影像学异常并非该病的必要表型,确诊有赖于基因检测。CTNNB1的3个新变异的鉴定扩展了NEDSDV的致病性变异谱。

Objective To investigate the clinical characteristics and genetic variants of children with neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). Methods A retrospective analysis was performed on the clinical manifestations, laboratory examinations, and genetic testing of 5 NEDSDV children diagnosed in the rehabilitation department of Nanjing Children's Hospital from 2014 to 2020, and the clinical manifestations and genetic characteristics of the patients were summarized together with literature review. Results All the five patients showed features of global developmental delay, microcephaly and spastic diplegia. Among them, patients 1, 2, 3, and 5 all had strabismus, and patient 5 had severe congenital retinal exudative abnormalities. Genetic testing identified de novo heterozygous mutations of CTNNB1 gene in all of the five patients, and all of them were truncated mutations (including nonsense and frameshift mutations), of which c.478_479insTAAATGA, c.1973dupT and c.625G>T were newly discovered mutations. Compared with 39 cases of genetically diagnosed patients reported abroad from 2001 to 2020 (including 5 adult cases), all but one child in this study had a slightly thinner corpus callosum, the other four cases showed no significant brain imaging abnormalities, and retinopathy was relatively rare. Conclusions Global developmental delay accompanied by microcephaly and spastic diplegia can be an indication for the suspected diagnosis of NEDSDV, while ocular lesions and brain imaging abnormalities are not necessary phenotypes for clinical diagnosis, and confirmation of diagnosis depends on genetic testing. The identification of three novel variants of CTNNB1 expands the pathogenic variants spectrum of NEDSDV.