Stickler Syndrome and VCAN Vitreoretinopathies (Erosive Vitreoretinopathy and Wagner Syndrome): Clinical Approach and Genetic Studies

Hereditary vitreoretinopathies (HVRs) are genetically based disorders affecting the vitreous and retina, potentially leading to severe vision loss. This review focuses on two major subtypes of HVRs: Stickler syndrome (SS) and VCAN-related vitreoretinopathies (primarily Wagner syndrome and erosive vitreoretinopathy [ERVR]). Stickler syndrome is a multisystemic collagenopathy typically caused by mutations in collagen genes such as COL2A1 and COL11A1. It is characterized by distinctive ocular findings (notable vitreous anomalies, high myopia, and an increased risk of retinal detachment), along with craniofacial, auditory, and skeletal manifestations. VCAN-related vitreoretinopathies result from mutations in the VCAN gene, which encodes the extracellular matrix proteoglycan versican. These conditions are typically characterized by specific ocular features, such as an ‘optically empty vitreous’ (as seen in Wagner syndrome), and generally lack prominent systemic manifestations. This review discusses the molecular genetic basis, detailed clinical phenotypes, and key elements for differential diagnosis of both disease groups, along with current ophthalmologic management strategies. Furthermore, genetic diagnostic methods used in these complex disorders, their diagnostic yields, genotype-phenotype correlations, diagnostic challenges, and future research directions are explored. Early and accurate diagnosis—especially when supported by molecular genetic testing—is vital for appropriate patient monitoring, prophylactic treatment planning to prevent complications such as retinal detachment, and genetic counseling for affected family members. A deeper understanding of these disorders will be achievable through ongoing research in ocular genetics and multidisciplinary approaches.