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Wagner Syndrome: for professionals

Overview

IncidenceRare, approximately 300 cases described world-wide
InheritanceAutosomal dominant
Genes Involved (OMIM No.)VCAN (#143200)
SymptomsGradual decline in visual acuity
Nyctalopia
Visual field constriction
Ocular FeaturesProgressive vitreoretinal degeneration
Retinal changes including lattice degeneration and increased risk of detachment
Presenile posterior subcapsular cataracts
Key InvestigationsSlit lamp and fundoscopy
OCT
Fluorescein angiography
ERG
Visual field testing
B scan
Genetic TestingWhole genome sequencing
ManagementOcular:
Regular ophthalmic monitoring
Management of complications e.g. cataracts, retinal detachment
Therapies under ResearchOngoing research includes natural history studies and investigations into potential preventive measures for retinal detachment.

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Clinical phenotype

Wagner Syndrome is a rare inherited disorder characterised by abnormalities affecting the vitreous body and the retina. It presents significant clinical heterogeneity and typically manifests in early to mid-adulthood, often between the second and fourth decades of life.1,2

Presenting features

Ocular:

  • Onset: Early to mid-adulthood, typically asymptomatic until the development of vitreous or retinal detachment issues.
  • Bilateral Symmetry
  • Visual Disturbances: Floaters, nyctalopia, visual field constriction, and progressive visual impairment.
  • Vitreous Degeneration: Progressive vitreous degeneration beginning during early adolescence, characterised by avascular vitreous cortex remnants adherent to the retina (vitreous veils) and liquefaction of the vitreous.3
  • Retinal Changes: Retinal pigment condensation, vascular sheathing, pigmented lattice degeneration, and later chorioretinal atrophy in the retinal periphery, leading to nyctalopia and visual field constriction.
  • Increased Risk of Retinal Detachment: Can be tractional due to tangential shortening of vitreoretinal adhesions or rhegmatogenous due to retinal breaks allowing liquefied vitreous to enter the potential subretinal space.
  • Presenile Posterior Subcapsular Cataracts: Often bilateral.
  • Myopia and Astigmatism: Commonly observed, potentially due to abnormal vitreous structure.

Fundus

  • Optically Empty Vitreous: The vitreous cavity appears empty on examination due to liquefaction.1
  • Vitreous Veils and Strands: Presence of avascular vitreous cortex remnants adherent to the retina.
  • Retinal Pigment Condensation: Pigmentary changes in the retina, often observed in the periphery.
  • Vascular Sheathing: Sheathing of retinal vessels, indicating vascular abnormalities.
  • Pigmented Lattice Degeneration: Degenerative changes in the retinal lattice, marked by pigmentation.
  • Chorioretinal Atrophy: Progressive atrophy of the choroid and retina, particularly in the periphery.
  • Retinal Detachment: Increased risk of tractional or rhegmatogenous retinal detachment.
  • Peripheral Retinal Changes: Pigmentary degeneration and atrophy in the peripheral retina.
  • Ectopic Fovea: Displacement of the fovea leading to an increased angle kappa.
  • Pigment Clumping: Diffuse or localised clumping of pigment, which can resemble retinitis pigmentosa.
  • Vascular Misplacement: Retinal vessels may appear dragged or show a ‘situs inversus’ configuration.

Genetics

Gene: Mutations in the versican gene (VCAN) located on chromosome 5q14.3.

  • OMIM No.: #143200
  • Inheritance Pattern: Autosomal dominant
  • Effect: Versican is crucial for the structure and function of the extracellular matrix, impacting tissue elasticity, cell migration, and proliferation. Pathogenic variants in Wagner Syndrome alter the interaction of versican with matrix components like hyaluronic acid, affecting the vitreous body’s properties and contributing to the ocular abnormalities observed.4-7

Further information about each gene can be found on OMIM and Medline Plus.

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Key investigations

Ocular

  1. Optical Coherence Tomography (OCT): Reveals significant thinning of nearly all retinal layers consistent with chorioretinal atrophy, and detects retinal detachment if present.8,9
  2. Fluorescein Angiography: Highlights peripheral vascular anomalies and chorioretinal atrophy.10
  3. Full-field Electroretinogram (ERG): Shows reduced a-wave and b-wave amplitudes, indicating varying degrees of rod and cone system involvement.
  4. Visual Field Testing: Detects peripheral field loss.
  5. Ultrasound B-Scan: May demonstrate increased axial length leading to myopia.
  6. Genetic Testing: Identification of pathogenic variants in the VCAN gene

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Diagnosis

The presence of characteristic vitreous abnormalities, retinal changes, and high myopia, along with a positive family history, may suggest Wagner syndrome. A definitive diagnosis is established through genetic testing, identifying pathogenic VCAN mutations.

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Differential Diagnoses

Differential diagnoses include Erosive Vitreoretinopathy (ERVR), Stickler Syndrome, Jansen Syndrome, and Autosomal Dominant Exudative Vitreoretinopathy (FEVR).

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Management

  • Regular Ophthalmic Follow-up: Essential for early detection and management of complications such as retinal detachment.
  • Refractive Error Correction: Spectacles or contact lenses for myopia and astigmatism.
  • Lifestyle Modifications: Regular eye examinations, avoidance of high-risk activities, and smoking cessation to minimise risk of complications.
  • Surgical Management: May include vitrectomy and retinal detachment repair, phacoemulsification, and intraocular lens implantation for cataract. Referral to appropriate specialists is necessary.11

Family management and counselling

Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Genetic counsellors and Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients and their parents in clinic. They provide emotional and practical support to help patients and parents deal with the diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist centre

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research.

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Current research

Research into Wagner syndrome focuses on understanding the molecular mechanisms underlying the condition and exploring potential gene therapies. Advances in genetic testing and targeted treatments aim to improve diagnostic accuracy and patient outcomes.

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Further information and support

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References

  1. Graemiger RA, Niemeyer G, Schneeberger SA, Messmer EP. Wagner vitreoretinal degeneration. Follow-up of the original pedigree. Ophthalmology. 1995;102:1830-9.
  2. Meredith SP, Richards AJ, Flanagan DW, Scott JD, Poulson AV, Snead MP. Clinical characterisation and molecular analysis of Wagner syndrome. Br J Ophthalmol. 2007;91:655-9. doi: 10.1136/bjo.2006.104406.
  3. Mukhopadhyay A, Nikopoulos K, Maugeri A, et al. 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;47(8):3565-3572. doi:10.1167/iovs.06-0141.
  4. Brézin AP, Nedelec B, Barjol A, Rothschild PR, Delpech M, Valleix S. A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features. Mol Vis. 2011;17:1669-78.
  5. Mukhopadhyay A, Nikopoulos K, Maugeri A, de Brouwer APM, van Nouhuys CE, Boon CJF, et al. 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;47:3565-72. doi: 10.1167/iovs.06-0141.
  6. Brown DM, Graemiger RA, Hergersberg M, et al. Genetic linkage of Wagner disease and erosive vitreoretinopathy to chromosome 5q13-14. Arch Ophthalmol. 1995;113(5):671-675. doi:10.1001/archopht.1995.01100050139045.
  7. 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;12:350-355.
  8. Rothschild PR, Burin-des-Roziers C, Audo I, Nedelec B, Valleix S, Brézin AP. Spectral-domain optical coherence tomography in Wagner syndrome: characterization of vitreoretinal interface and foveal changes. Am J Ophthalmol. 2015;160:1065-1072.e1. doi: 10.1016/j.ajo.2015.08.012.
  9. Bleicher ID, Garg I, Hoyek S, Place E, Miller JB, Patel NA. Widefield Swept-Source Optical Coherence Tomography Angiography Findings in Wagner Syndrome. Retin Cases Brief Rep. 2022 Aug 11.
  10. Thomas AS, Branham K, Van Gelder RN, et al. Multimodal Imaging in Wagner Syndrome. Ophthalmic Surg Lasers Imaging Retina. 2016;47(6):574-579. doi:10.3928/23258160-20160601-10.
  11. Sung JY, Lee MW, Won YK, Lim HB, Kim JY. Clinical characteristics and prognosis of Total Rhegmatogenous retinal detachment: a matched case-control study. BMC Ophthalmol. 2020;20(1):286. Published 2020 Jul 13. doi:10.1186/s12886-020-01560-4.

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Updated on June 3, 2024
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