Wagner syndrome

Wagner syndrome is an inherited disorder that is characterized by vision loss that worsens over time. This condition affects the thick, clear fluid that fills the eyeball (the vitreous) and the specialized light-sensitive tissue that lines the back of the eye (retina). The signs and symptoms of the condition typically begin in early adolescence.

In people with Wagner syndrome, the vitreous breaks down over time (degenerates), becoming watery and thin. This can lead to changes in the retina, which is attached to the vitreous by tiny fibers. The retina and the network of blood vessels beneath the retina (choroid) may begin to waste away (atrophy). These changes can cause vision problems, including difficulty seeing in low light (night blindness). Some affected individuals have blurred vision because of an abnormality called ectopic fovea. In people with ectopic fovea, the part of the retina that is responsible for sharp central vision (the fovea) is dragged out of place due to abnormal connections (adhesions) between the vitreous and the retina. In some affected individuals, the retina separates from the back of the eye (retinal detachment), which can cause severe vision loss.  

Additional signs and symptoms of Wagner syndrome can include a clouding of the lens of the eye (cataract), nearsightedness (myopia), increased pressure in the eyes (glaucoma), and atrophy of the nerves that carry information from the eyes to the brain (optic atrophy).

The amount of vision loss in people with Wagner syndrome can vary. Some affected individuals maintain near-normal vision, while others develop severe vision loss.

Because Wagner syndrome affects both the retina and the vitreous, it belongs to a group of disorders called hereditary vitreoretinopathies. Other examples of disorders within this group are Stickler syndrome and familial exudative vitreoretinopathy. Another condition called erosive vitreoretinopathy is very similar to Wagner syndrome. Many researchers now consider this condition to be a variant of Wagner syndrome.

Wagner syndrome is a rare disorder. Fewer than 1 in 1 million people are estimated to have the condition. Approximately 100 affected individuals have been reported in the scientific literature.

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the VCAN gene cause Wagner syndrome. The VCAN gene provides instructions for making a protein called versican core protein. This protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Versican core protein interacts with many of these molecules to provide structure and support to the extracellular matrix. Within the eye, versican core portein helps maintain the gel-like consistency of the vitreous.

The pathogenic variants in the VCAN gene that are associated with Wagner syndrome cause cells to produce a version of the protein that does not function properly. As a result, there is not enough functioning versican core protein to keep the vitreous in its gel-like state. This lack of stability in the vitreous affects the retina and contributes to the vision problems that are characteristic of this disorder. Researchers are working to learn more about how pathogenic variants in the VCAN gene affect other tissues.  

Genetic Testing Information

• Genetic Testing Registry: Wagner disease

Genetic and Rare Diseases Information Center

• Wagner disease

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• WAGNER VITREORETINOPATHY; WGVRP

Scientific Articles on PubMed

• PubMed

• Araujo JR, Tavares-Ferreira J, Estrela-Silva S, Rocha P, Brandao E, Faria PA, Falcao-Reis F, Rocha-Sousa A. WAGNER syndrome: anatomic, functional and genetic characterization of a Portuguese family. Graefes Arch Clin Exp Ophthalmol. 2018 Jan;256(1):163-171. doi: 10.1007/s00417-017-3800-0. Epub 2017 Oct 25. Citation on PubMed
• Ghoraba HH, Sears J, Traboulsi EI. Hereditary Vitreoretinopathies: Molecular Diagnosis, Clinical Presentation and Management. Clin Exp Ophthalmol. 2025 Apr;53(3):281-291. doi: 10.1111/ceo.14494. Epub 2025 Jan 21. Citation on PubMed
• Kloeckener-Gruissem B, Bartholdi D, Abdou MT, Zimmermann DR, Berger W. Identification of the genetic defect in the original Wagner syndrome family. Mol Vis. 2006 Apr 17;12:350-5. Citation on PubMed
• Meredith SP, Richards AJ, Flanagan DW, Scott JD, Poulson AV, Snead MP. Clinical characterisation and molecular analysis of Wagner syndrome. Br J Ophthalmol. 2007 May;91(5):655-9. doi: 10.1136/bjo.2006.104406. Epub 2006 Oct 11. Citation on PubMed or Free article on PubMed Central
• Miyamoto T, Inoue H, Sakamoto Y, Kudo E, Naito T, Mikawa T, Mikawa Y, Isashiki Y, Osabe D, Shinohara S, Shiota H, Itakura M. Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2726-35. doi: 10.1167/iovs.05-0057. Citation on PubMed
• Mukhopadhyay A, Nikopoulos K, Maugeri A, de Brouwer AP, van Nouhuys CE, Boon CJ, Perveen R, Zegers HA, Wittebol-Post D, van den Biesen PR, van der Velde-Visser SD, Brunner HG, Black GC, Hoyng CB, Cremers FP. Erosive vitreoretinopathy and wagner disease are caused by intronic mutations in CSPG2/Versican that result in an imbalance of splice variants. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3565-72. doi: 10.1167/iovs.06-0141. Citation on PubMed
• Ronan SM, Tran-Viet KN, Burner EL, Metlapally R, Toth CA, Young TL. Mutational hot spot potential of a novel base pair mutation of the CSPG2 gene in a family with Wagner syndrome. Arch Ophthalmol. 2009 Nov;127(11):1511-9. doi: 10.1001/archophthalmol.2009.273. Citation on PubMed or Free article on PubMed Central
• Szeligowski T, Cehajic-Kapetanovic J, Raji S, Purohit R, Amin H, Patel CK, Xue K. Multimodal Evaluation and Management of Wagner Syndrome-Three Patients from an Affected Family. Genes (Basel). 2024 Sep 8;15(9):1178. doi: 10.3390/genes15091178. Citation on PubMed