Snowflake Vitreoretinal Degeneration Is Clinically and Genetically Distinct From the Stickler Syndromes and Wagner Disease

Abstract

Abstract: : Purpose: To study the ocular findings and systemic features in the original Snowflake family and determine if disease in this family segregates with known genes causing vitreoretinal degeneration. Methods: Clinical data were collected on 26 family members by history and examination. Thirteen of the 26 total family members underwent prospective examination. Linkage to known vitreoretinal degeneration loci (COL2A1, COL11A1, and the Wagner disease locus) was evaluated using short tandem repeat markers. Results: Six of the thirteen prospectively examined subjects had Snowflake vitreoretinal degeneration. Corneal guttae (4/5; 80%), early onset cataract (5/6; 83%), fibrillar vitreous degeneration (6/6; 100%), and peripheral retinal abnormalities (5/6; 83%) including minute crystalline-like deposits called snowflakes (4/6; 67%) were common. Retinal detachment was seen in 1 of 6 (17%) of these prospectively examined subjects. A total of fourteen affected subjects were identified within the family and 3 (21%) had developed retinal detachment. Orofacial features, early-onset hearing loss, and arthritis typical of Stickler syndrome were absent. Linkage to known vitreoretinal degeneration loci was excluded. Conclusions: The absence of vitreous gel in the retrolental space and presence of fibrillar vitreous degeneration were consistent with the vitreous structure reported for collagen 11A1 (COL11A1) but not collagen 2A1 (COL2A1) mutations. The absence of systemic features was characteristic of the vitreoretinopathies linked to chromosome 5q13 (Wagner disease and erosive vitreoretinopathy) and mutations in exon 2 of the COL2A1 gene. Snowflakes in the peripheral retina and the absence of nyctalopia, posterior chorioretinal atrophy, and tractional retinal detachment were inconsistent with the chromosome 5q13 vitreoretinopathies. The association of Fuchs’ corneal endothelial dystrophy found in this family has not been previously reported in other vitreoretinal degenerations. These findings and the exclusion of known genetic loci suggest Snowflake is a clinically and genetically distinct vitreoretinal degeneration.

Keywords: retinal degenerations: hereditary • retinal detachment • genetics