Visual Function and Ophthalmological Findings in CHARGE Syndrome: Revision of Literature, Definition of a New Clinical Spectrum and Genotype Phenotype Correlation

Abstract

CHARGE syndrome (CS) is a rare genetic disease causing multiple anatomical defects and sensory impairment. Visual function is usually reported by caregivers and has never been described with a structured behavioral assessment. Our primary objective was to describe ocular abnormalities, visual function and genotype–ocular-phenotype correlation in CS. A prospective monocentric cohort study was performed on 14 children with CS carrying pathogenic CHD7 variants. All children underwent ophthalmological evaluation and structured behavioral assessment of visual function. The VISIOCHARGE questionnaire was administered to parents. Colobomas were present in 93% of patients. Genotype–phenotype correlation documented mitigated features in a subset of patients with intronic pathogenic variants predicted to affect transcript processing, and severe features in patients with frameshift/nonsense variants predicting protein truncation at the N-terminus. Abnormal visual function was present in all subjects, with different degrees of impairment. A significant correlation was found between visual function and age at assessment (p-value = 0.025). The present data are the first to characterize visual function in CS patients. They suggest that hypomorphic variants might be associated with milder features, and that visual function appears to be related to age. While studies with larger cohorts are required for confirmation, our data indicate that experience appears to influence everyday use of visual function more than ocular abnormalities do.

Cortical Visual Impairment in CDKL5 Deficiency Disorder

“…These aspects are typically considered to be mediated by subcortical structures but, even if relatively preserved, were still frequently affected in most patients. Although this was not systematically explored in our patients using imaging, the impairment of these aspects is likely to be in relation to the involvement in subcortical areas such as basal ganglia and lateral geniculate nucleus, as described by Mazziotti ( 8 ) and Lupori ( 31 ) in CDD animal models. It is of interest that while tracking horizontally and, partly, vertically was relatively spared, when increasing the complexity of action, requiring to track in a circle, most of the patients with CDD showed increasing difficulties.…”

“…Most information on aspects of visual function comes from the ophthalmologic assessment or from caregivers' observation. In this study, using a battery of tests that have been specifically designed for young children with relatively poor collaboration, easy to be performed even in young children with multisensory or cognitive impairment ( 29 – 31 ), we were able to perform a detailed assessment in a cohort with a wide range of age and severity.…”

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

“…Moreover, photoreceptor defects may take years to become evident, and long-term studies on visual acuity in adults with CHARGE syndrome have not been reported. A recent study of visual function in 14 children with CHARGE syndrome found that all had some degree of visual impairment, even in the absence of structural malformations such as coloboma (Onesimo et al, 2021). These results suggest that the visual system disruptions associated with CHARGE syndrome may indeed involve retinal cell type defects in addition to problems with ocular morphogenesis.…”

“…However, CHARGE syndrome is also associated with other ocular complications, including microphthalmia, optic nerve hypoplasia, nystagmus, cataracts, amblyopia, microcornea, strabismus and rarely angle closure defects and retinal detachment (Aramaki et al, 2006; Guirgis and Lueder, 2003; Lalani et al, 2006; Natung et al, 2014; Russell-Eggitt et al, 1990; Strömland et al, 2005; A L Tellier et al, 1998; A.L Tellier et al, 1998). A recent study of visual function in 14 CHARGE syndrome patients found that all had some degree of visual impairment, even in the absence of structural malformations such as coloboma (Onesimo et al, 2021). These results suggest that the visual system disruptions associated with CHARGE syndrome may involve retinal developmental defects in addition to problems with ocular morphogenesis.…”

CHARGE Syndrome Associated with Ocular Abnormalities: A Case Report with Treatment of Amblyopia and Refractive Correction

“… 6 , 7 , 9 , 10 However, there is lack of detailed information in other aspects of visual function due to some difficulties in participation of CS patients. 11 Among these studies, there were no assessments of refractive error corrections and/or details about the treatment of amblyopia. Thus, the aim of this case report is to examine in details the visual function of a young girl with CS having bilateral amblyopia and provide her with the refractive correction including a treatment plan of amblyopia.…”