Detailed structural abnormalities associated with a novel VCAN variant in a family with versican vitreoretinopathy.

Purpose: To understand the retina micropathology in a family with a novel variant in VCAN.

Methods: Two sisters ages 16 (proband) and 18 years old and their 48-year-old father underwent comprehensive ophthalmic evaluations. Multimodal imaging was performed with spectral domain optical coherence tomography, ultrawide field short-wavelength fundus autofluorescence, and pseudocolor imaging.

Results: Cataracts were present in the sisters along with a penetrant retinal phenotype in all three patients with vitreoretinal ring opacities and traction, peripheral pigmentary clumps, lattice-like features, retinoschisis, foveal ectopia, and nasal displacement of vessels. There were regions with inner retinal thinning with spared outer retina, likely a consequence of vitreoretinal traction, that contrasted with large areas of profound photoreceptor degeneration, but with a rather normal or thickened inner retina. A previously unreported heterozygous variant in intron 7 of VCAN (c.4004-2A>C) segregated with the phenotype in the proband and her father.

Conclusions: Segregation of a versican-associated vitreoretinopathy supports the pathogenicity of the VCAN variant. The patterns of structural abnormalities support classical mechanisms of disease that involve local vitreoretinal traction, as well as possible alternative developmental and/or degenerative changes of the retina, RPE, and/or choroid that result from the primary molecular defect.