关键词: 全面性发育迟缓, 痉挛性双瘫, 视觉缺陷, CTNNB1基因

Abstract:

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.

Key words: global developmental delay, spastic diplegia, visual defects, CTNNB1 gene