Cerebral Visual Impairment: genetic diagnoses and phenotypic associations

Abstract

ABSTRACTBackgroundCerebral visual impairment (CVI) is the commonest form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders.MethodsWe carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100,000 Genomes Project (100KGP).Results158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, whilst the remaining 148 are candidate genes for this phenotype. Gene Ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggest that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI.ConclusionThis study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.What is known about the subject?CVI is the most prevalent form of paediatric-onset visual impairment in the developed world.CVI commonly occurs alongside other neurodevelopmental phenotypes such as epilepsies, global developmental delay, cerebral palsy, ADHD and autism.CVI is known to have genetic aetiology, which is often undiagnosed.What this study adds?This study reports CVI-associated genetic diagnoses and phenotypic associations for two large cohortsGene ontology annotations have been analysed for candidate CVI genesHow this study might affect research, practice or policyThis study has implications for genetic testing in children with CVIThis study has implications for CVI screening in children with a genetic diagnosis