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.
Highlights
CHARGE syndrome (CS; OMIM 214800) is a rare genetic disorder with an estimated incidence of 1/12,000
All subjects met the clinical criteria for CS and had been molecularly confirmed to carry heterozygous CHD7 variants classified as pathogenic/likely pathogenic
Ophthalmological Evaluation All patients had some degree of ocular abnormality, as summarized in Tables 1 and 2
Summary
CHARGE syndrome (CS; OMIM 214800) is a rare genetic disorder with an estimated incidence of 1/12,000. The term ‘CHARGE’ is an acronym for the most striking clinical features of the syndrome, involving coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary malformation and ear abnormalities [1]. The visual system is frequently affected, with coloboma and other ocular abnormalities being present in up to 90% of patients [8]. The involvement of the macula is responsible for significant reductions in central visual acuity. Anterior segment abnormalities such as microcornea and cataracts are commonly described and may be associated with other less frequent features, including severe refractive errors, strabismus and ptosis [9]. Visual acuity is reported as lower than 20/60 in evaluable subjects [8,9,10,11,12], but more detailed information on acuity and other aspects of visual function is limited because of the difficulty in obtaining the full participation of CS patients who, by definition, have a complex clinical presentation
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