Ophthalmic Manifestations of NAA10-Related and NAA15-Related Neurodevelopmental Syndrome: Analysis of Cortical Visual Impairment and Refractive Errors

Abstract

AbstractNAA10-related andNAA15-related neurodevelopmental syndrome, otherwise known as Ogden Syndrome, is known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations ofNAA10andNAA15mutations are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic mutations in theNAA10cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with pathogenic mutations in theNAA15cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in ourNAA10cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified between theNAA10andNAA15mutations. Our study includes novel neuroimaging of 13NAA10and 5NAA15probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions.