Costello Syndrome and Ophthalmologic Issues: Unveiling the Unseen

Costello syndrome (CS) is an ultra-rare condition belonging to the RASopathies, a group of disorders characterized by aberrant RAS/MAPK pathway signaling, which is involved in ocular development and in some eye pathologies. However, only a few studies assessing the ophthalmic features of individuals with CS are available. In this article, we describe the main ophthalmic anomalies and MRI findings in a large cohort of CS patients and compare our data with theliterature. 21 individuals with CS were enrolled and performedvisual acuity and refractive error assessment, intraocular pressure (IOP) evaluation, ocular motility examination, anterior segment inspection, fundus examination, macular optical coherence and corneal tomography, and brain MRI with the measurement of optic nerve thickness. A high prevalence of refractive errors was observed (90%), amblyopia, with best-corrected visual acuity below 20/40 in at least one eye in all assessed cases. Strabismus was also described in the present cohort (95%), with exotropia, esotropia, and hypertropia equally present. Moreover, 66.7% of our patients presented nystagmus. OCT was normal in all cases performed (6). Eighteen individuals underwent brain MRI, and 63% of them showed an altered optic nerve thickness. We described for the first time to date bilateral optic nerve thickness reduction assessed through MRI in CS. Moreover, in our cohort, we detect a high prevalence of amblyopia, refractive errors, and nystagmus across all ages. These findings support the implementation of an early ophthalmologic assessment and management in patients with CS to prevent deterioration of visual functions; therefore, improving overall quality of life.