Prevalence and phenotypes/genotypes of CRB1 retinal dystrophies

Abstract

Purpose : Mutations in CRB1 are classically associated with Leber congenital amaurosis (LCA). A macular phenotype has been recently identified. Herein, we evaluate the different phenotypes and their causal mutations.

Methods : All patients with biallelic CRB1 mutations known at our academic institution were included. The distinction between LCA and early-onset retinitis pigmentosa (RP) was based on the presence of a congenital nystagmus and the age of night blindness (< 2 years). A phenotype of isolated maculopathy was retained in cases without night blindness, and preserved peripheral visual fields, peripheral retina and vessel calibers on color and/or autofluorescence photographs.

Results : Among the 4267 families included in our database, 28 families had CRB1-related retinal dystrophies. Eight families (9 patients, 14.5% of all LCA patients) had an LCA with severe visual loss (hand motion to 20/400). Fifteen patients (15 families, 4% of all RP cases) had a RP with an early-onset and a severe visual loss during the first decade. In LCA and RP phenotypes, visual loss is consistent with the macular involvement with hyperreflective lesions on optical coherence tomography and preserved macular thickness despite photoreceptor loss. A macular phenotype was found in 5 patients (four families), 4 of them have a visual acuity below 20/40 in both eyes. All patients with maculopathy carry the c.498_506del in one allele (5.7% of inherited macular dystrophies). All RP patients have at least one missense mutation in CRB1. Patients with LCA have at least one or two frameshifts in CRB1, except for two patients.

Conclusions : Biallellic CRB1 mutations cause LCA or early-onset RP with early and severe central visual loss. Macular dystrophies account for more than 16% of CRB1-related retinal dystrophies and for 5.7% of inherited macular dystrophies. Ophthalmologists should be aware of the range of CRB1 phenotypes, characterized by specific fundus and autofluorescence macular patterns.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.