Skip to main content
SpringerLink
Log in

Juvenile X-Linked Retinoschisis and Hereditary Vitreoretinopathies

  • Living reference work entry
  • First Online:
Albert and Jakobiec's Principles and Practice of Ophthalmology

  • 30 Accesses

Abstract

Hereditary vitreoretinopathies are a group of a rare, heterogenous disorders that are primarily characterized by degeneration of the vitreous and the retina. Some of these conditions, such as X-linked retinoschisis, consistently present with characteristic features making them more easily identifiable, whereas others represent a spectrum of disease that is more easily diagnosed with ancillary clinical and genetic testing. There is a broad spectrum of ocular, and sometimes systemic, findings with overlapping features in patients with hereditary vitreoretinopathies. Patients with unexplained early onset cataract or retinal detachment should be carefully evaluated for any additional findings. Genetic testing will likely continue to play a critical role in definitive diagnosis and perhaps expansion of known phenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Eksandh LC, Ponjavic V, Ayyagari R, et al. Phenotypic expression of juvenile X-linked retinoschisis in Swedish families with different mutations in the XLRS1 gene. Arch Ophthalmol. 2000;118:1098–104.

    Article  CAS  PubMed  Google Scholar 

  2. Hiriyanna KT et al. Searching for Genotype-Phenotype Correlations in X-Linked Juvenile Retinoschisis. In: Anderson R.E., LaVail M.M., Hollyfield J.G. (eds) New Insights Into Retinal Degenerative Diseases. Springer, Boston, MA. 2001.

    Google Scholar 

  3. Menke MN, Feke GT, Hirose T. Effect of aging on macular features of X-linked retinoschisis assessed with optical coherence tomography. Retina. 2011;31:1186–92.

    Article  PubMed  Google Scholar 

  4. Cukras CA, Huryn LA, Jeffrey BG, Turriff A, Sieving PA. Analysis of anatomic and functional measures in X-linked retinoschisis. Invest Ophthalmol Vis Sci. 2018;59:2841–7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rao P, Robinson J, Yonekawa Y, et al. Wide-field imaging of nonexudative and exudative congenital X-linked Retinoschisis. Retina. 2016;36:1093–100.

    Article  PubMed  Google Scholar 

  6. George NDN. Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol (1960). 1996;114:274–80.

    Article  CAS  Google Scholar 

  7. Kellner UU. X-linked congenital retinoschisis. Graefes Arch Clin Exp Ophthalmol. 1990;228:432–7.

    Article  CAS  PubMed  Google Scholar 

  8. Roesch MTEC, Gibson AE, Weber BH. The natural history of X-linked retinoschisis. Can J Ophthalmol. 1998;33:149–58.

    CAS  PubMed  Google Scholar 

  9. Fahim AT, Ali N, Blachley T, Michaelides M. Peripheral fundus findings in X-linked retinoschisis. Br J Ophthalmol. 2017;101(11):1555–1559.

    Google Scholar 

  10. Peachey NSN. Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis. Arch Ophthalmol (1960). 1987;105:513–6.

    Article  CAS  Google Scholar 

  11. Brasil OF, da Cunha AL, de Castro MB, Japiassú RM. Macular hole secondary to X-linked juvenile retinoschisis. Ophthalmic Surg Lasers Imaging. 2011;42 Online:e4–5.

    Google Scholar 

  12. Shanmugam MP, Nagpal A. Foveal schisis as a cause of retinal detachment secondary to macular hole in juvenile X-linked retinoschisis. Retina. 2005;25:373–5.

    Article  PubMed  Google Scholar 

  13. Shukla D, Rajendran A, Gibbs D, Suganthalakshmi B, Zhang K, Sundaresan P. Unusual manifestations of x-linked retinoschisis: clinical profile and diagnostic evaluation. Am J Ophthalmol. 2007;144:419–23. e2.

    Article  CAS  PubMed  Google Scholar 

  14. Garg SJ, Lee HC, Grand MG. Bilateral macular detachments in X-linked retinoschisis. Arch Ophthalmol. 2006;124:1053–5.

    Article  PubMed  Google Scholar 

  15. Hotta Y, Nakamura M, Okamoto Y, Nomura R, Terasaki H, Miyake Y. Different mutation of the XLRS1 gene causes juvenile retinoschisis with retinal white flecks. Br J Ophthalmol. 2001;85:238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. de Jong PT, Zrenner E, van Meel GJ, Keunen JE, van Norren D. Mizuo phenomenon in X-linked retinoschisis: pathogenesis of the Mizuo phenomenon. Arch Ophthalmol. 1991;109:1104–8.

    Article  PubMed  Google Scholar 

  17. Vincent A, Shetty R, Yadav N, Shetty B. Foveal schisis with Mizuo phenomenon: etio-pathogenesis of tapetal reflex in X-linked retinoschisis. Eye. 2009;23:1240.

    Article  CAS  PubMed  Google Scholar 

  18. Pearson R, Jagger J. Sex linked juvenile retinoschisis with optic disc and peripheral retinal neovascularisation. Br J Ophthalmol. 1989;73:311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ewing C, Cullen A. Fluorescein angiography in X-chromosomal maculopathy with retinoschisis (juvenile hereditary retinoschisis). Can J Ophthalmol. 1972;7:19.

    CAS  PubMed  Google Scholar 

  20. Eriksson U, Larsson E, Holmstrom G. Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis. Acta Ophthalmol Scand. 2004;82:218–23.

    Article  PubMed  Google Scholar 

  21. Prenner JL, Capone A Jr, Ciaccia S, Takada Y, Sieving PA, Trese MT. Congenital X-linked retinoschisis classification system. Retina. 2006;26:S61–4.

    Article  PubMed  Google Scholar 

  22. Apushkin MA, Fishman GA, Janowicz MJ. Correlation of optical coherence tomography findings with visual acuity and macular lesions in patients with X-linked retinoschisis. Ophthalmology. 2005;112:495–501.

    Article  PubMed  Google Scholar 

  23. Gregori NZ, Berrocal AM, Gregori G, et al. Macular spectral-domain optical coherence tomography in patients with X linked retinoschisis. Br J Ophthalmol. 2009;93:373–8.

    Article  CAS  PubMed  Google Scholar 

  24. Molday RS, Kellner U, Weber BHF. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012;31:195–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lesch B, Szabó V, Kánya M, et al. Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis. Mol Vis. 2008;14:2321–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Sieving PA, Bingham EL, Kemp J, Richards J, Hiriyanna K. Juvenile X-linked retinoschisis from XLRS1 Arg213Trp mutation with preservation of the electroretinogram scotopic b-wave. Am J Ophthalmol. 1999;128:179–84.

    Article  CAS  PubMed  Google Scholar 

  27. Pennesi ME, Birch DG, Jayasundera KT, et al. Prospective evaluation of patients with X-linked Retinoschisis during 18 months. Invest Ophthalmol Vis Sci. 2018;59:5941–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Kjellström S, Vijayasarathy C, Ponjavic V, Sieving PA, Andréasson S. Long-term 12 year follow-up of X-linked congenital retinoschisis. Ophthalmic Genet. 2010;31:114–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Apushkin MAMA. Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis. Retina (Philadelphia, PA). 2005;25:612–8.

    Article  Google Scholar 

  30. Bowles K, Cukras C, Turriff A, et al. X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects. Invest Ophthalmol Vis Sci. 2011;52:9250–6.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Andreoli MT, Lim JI. Optical coherence tomography retinal thickness and volume measurements in X-linked Retinoschisis. Am J Ophthalmol. 2014.

    Google Scholar 

  32. Sauer CG, Gehrig A, Warneke-Wittstock R, et al. Positional cloning of the gene associated with X-linked juvenile retinoschisis. Nat Genet. 1997;17:164–70.

    Article  CAS  PubMed  Google Scholar 

  33. Sieving PA, Yashar BM, Ayyagari R, et al. Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease. Trans Am Ophthalmol Soc. 1999;97:451–64; Discussion 64–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Clarke A. The genetic testing of children. Working Party of the Clinical Genetics Society (UK). J Med Genet. 1994;31:785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Inoue Y, Yamamoto S, Okada M, et al. X-linked retinoschisis with point mutations in the XLRS1 gene. Arch Ophthalmol. 2000;118:93–6.

    Article  CAS  PubMed  Google Scholar 

  36. Consortium R. Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis (XLRS). Hum Mol Genet. 1998;7:1185–92.

    Article  Google Scholar 

  37. Sergeev YV, Caruso RC, Meltzer MR, Smaoui N, MacDonald IM, Sieving PA. Molecular modeling of retinoschisin with functional analysis of pathogenic mutations from human X-linked retinoschisis. Hum Mol Genet. 2010;19:1302–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sergeev YV, Vitale S, Sieving PA, et al. Molecular modeling indicates distinct classes of missense variants with mild and severe XLRS phenotypes. Hum Mol Genet. 2013;22:4756–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bowles K, Cukras C, Turriff A, et al. X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects. Investig Ophthalmol Vis Sci. 2011;52:9250–6.

    Article  Google Scholar 

  40. Suganthalakshmi B, Shukla D, Rajendran A, Kim R, Nallathambi J, Sundaresan P. Genetic variations in the hotspot region of RS1 gene in Indian patients with juvenile X-linked retinoschisis. Mol Vis. 2007;13:611.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Li X, Ma X, Tao Y. Clinical features of X linked juvenile retinoschisis in Chinese families associated with novel mutations in the RS1 gene. Mol Vis. 2007;13:804.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ou J, Vijayasarathy C, Ziccardi L, et al. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer. J Clin Invest. 2015;125:2891–903.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Bush M, Setiaputra D, Yip CK, Molday RS. Cog-wheel octameric structure of RS1, the Discoidin domain containing retinal protein associated with X-linked Retinoschisis. PLoS One. 2016;11:e0147653.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Tolun G, Vijayasarathy C, Huang R, et al. Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina. Proc Natl Acad Sci U S A. 2016;113:5287–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Heymann JB, Vijayasarathy C, Huang RK, Dearborn AD, Sieving PA, Steven AC. Cryo-EM of retinoschisin branched networks suggests an intercellular adhesive scaffold in the retina. J Cell Biol. 2019;218:1027–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kjellstrom S, Bush RA, Zeng Y, Takada Y, Sieving PA. Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: long-term rescue from retinal degeneration. Invest Ophthalmol Vis Sci. 2007;48:3837–45.

    Article  PubMed  Google Scholar 

  47. Weber BH, Schrewe H, Molday LL, et al. Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure. Proc Natl Acad Sci. 2002;99:6222–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jablonski MM, Dalke C, Wang X, et al. An ENU-induced mutation in Rs1h causes disruption of retinal structure and function. Mol Vis. 2005;11:569–81.

    CAS  PubMed  Google Scholar 

  49. Testa F, Di Iorio V, Gallo B, et al. Carbonic anhydrase inhibitors in patients with X-linked retinoschisis: effects on macular morphology and function. Ophthalmic Genet. 2019;40:1–6.

    Article  CAS  Google Scholar 

  50. Andreuzzi P, Fishman GA, Anderson RJ. Use of a carbonic anhydrase inhibitor in X-linked retinoschisis: effect on cystic-appearing macular lesions and visual acuity. Retina. 2017;37:1555–61.

    Article  CAS  PubMed  Google Scholar 

  51. Apushkin MA, Fishman GA. Use of dorzolamide for patients with X-linked retinoschisis. Retina. 2006;26:741–5.

    Article  PubMed  Google Scholar 

  52. Genead MA, Fishman GA, Walia S. Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with X-linked retinoschisis. Arch Ophthalmol. 2010;128:190–7.

    Article  CAS  PubMed  Google Scholar 

  53. Gurbaxani A, Wei M, Succar T, McCluskey PJ, Jamieson RV, Grigg JR. Acetazolamide in retinoschisis: a prospective study. Ophthalmology. 2014;121:802–3.e3.

    Article  PubMed  Google Scholar 

  54. Thobani A, Fishman GA. The use of carbonic anhydrase inhibitors in the retreatment of cystic macular lesions in retinitis pigmentosa and X-linked retinoschisis. Retina (Philadelphia, PA). 2011;31:312.

    Article  CAS  Google Scholar 

  55. Verbakel SK, van de Ven JP, Le Blanc LM, et al. Carbonic anhydrase inhibitors for the treatment of cystic macular lesions in children with X-linked juvenile retinoschisis. Invest Ophthalmol Vis Sci. 2016;57:5143–7.

    Article  CAS  PubMed  Google Scholar 

  56. Walia S, Fishman GA, Molday RS, et al. Relation of response to treatment with dorzolamide in X-linked retinoschisis to the mechanism of functional loss in retinoschisin. Am J Ophthalmol. 2009;147:111–5.e1.

    Article  CAS  PubMed  Google Scholar 

  57. Zhour A, Bolz S, Grimm C, et al. In vivo imaging reveals novel aspects of retinal disease progression in Rs1h−/Y mice but no therapeutic effect of carbonic anhydrase inhibition. Vet Ophthalmol. 2012;15:123–33.

    Article  CAS  PubMed  Google Scholar 

  58. Bush RA, Zeng Y, Colosi P, et al. Preclinical dose-escalation study of intravitreal AAV-RS1 gene therapy in a mouse model of X-linked Retinoschisis: dose-dependent expression and improved retinal structure and function. Hum Gene Ther. 2016;27:376–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Park T, Wu Z, Kjellstrom S, et al. Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse. Gene Ther. 2009;16:916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cukras C, Wiley HE, Jeffrey BG, et al. Retinal AAV8-RS1 gene therapy for X-linked retinoschisis: initial findings from a phase I/IIa trial by intravitreal delivery. Mol Ther. 2018;26:2282–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Janssen A, Min SH, Molday LL, et al. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse. Mol Ther. 2008;16:1010–7.

    Article  CAS  PubMed  Google Scholar 

  62. Robin NH, Moran RT, Ala-Kokko L. Stickler syndrome. GeneReviews®[Internet]. Seattle: University of Washington; 2017.

    Google Scholar 

  63. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004;41:47–52.

    Article  PubMed  Google Scholar 

  64. Fincham GS, Pasea L, Carroll C, et al. Prevention of retinal detachment in stickler syndrome: the Cambridge prophylactic cryotherapy protocol. Ophthalmology. 2014;121:1588–97.

    Article  PubMed  Google Scholar 

  65. Carroll C, Papaioannou D, Rees A, Kaltenthaler E. The clinical effectiveness and safety of prophylactic retinal interventions to reduce the risk of retinal detachment and subsequent vision loss in adults and children with Stickler syndrome: a systematic review. Health Technol Assess. 2011;15(16):iii-xiv, 1–62.

    Google Scholar 

  66. Edwards AO. Clinical features of the congenital vitreoretinopathies. Eye. 2008;22:1233.

    Article  CAS  PubMed  Google Scholar 

  67. Hirose T, Lee KY, Schepens CL. Wagner’s hereditary vitreoretinal degeneration and retinal detachment. Arch Ophthalmol. 1973;89:176–85.

    Article  CAS  PubMed  Google Scholar 

  68. Seery CM, Pruett RC, Liberfarb RM, Cohen BZ. Distinctive cataract in the stickler syndrome. Am J Ophthalmol. 1990;110:143–8.

    Article  CAS  PubMed  Google Scholar 

  69. Snead M, McNinch A, Poulson A, et al. Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye. 2011;25:1389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Maumenee IH, Stoll HU, Mets M. The Wagner syndrome versus hereditary arthroophthalmopathy. Trans Am Ophthalmol Soc. 1982;80:349.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 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.

    Article  PubMed  Google Scholar 

  72. Brown DM, Graemiger RA, Hergersberg M, et al. Genetic linkage of Wagner disease and erosive vitreoretinopathy to chromosome 5q13-14. Arch Ophthalmol. 1995;113:671–5.

    Article  CAS  PubMed  Google Scholar 

  73. Miyamoto T, Inoue H, Sakamoto Y, et al. Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Invest Ophthalmol Vis Sci. 2005;46:2726–35.

    Article  PubMed  Google Scholar 

  74. Graemiger RA, Niemeyer G, Schneeberger SA, Messmer EP. Wagner vitreoretinal degeneration: follow-up of the original pedigree. Ophthalmology. 1995;102:1830–9.

    Article  CAS  PubMed  Google Scholar 

  75. Hirose T, Lee KY, Schepens CL. Snowflake degeneration in hereditary vitreoretinal degeneration. Am J Ophthalmol. 1974;77:143–53.

    Article  CAS  PubMed  Google Scholar 

  76. Lee MM, Ritter R III, Hirose T, Vu CD, Edwards AO. Snowflake vitreoretinal degeneration: follow-up of the original family. Ophthalmology. 2003;110:2418–26.

    Article  PubMed  Google Scholar 

  77. Kaufman SJ, Goldberg MF, Orth DH, Fishman GA, Tessler H, Mizuno K. Autosomal dominant vitreoretinochoroidopathy. Arch Ophthalmol. 1982;100:272–8.

    Article  CAS  PubMed  Google Scholar 

  78. Blair NP, Goldberg MF, Fishman GA, Salzano T. Autosomal dominant vitreoretinochoroidopathy (ADVIRC). Br J Ophthalmol. 1984;68:2–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Boulanger-Scemama E, Sahel J-A, Mohand-Said S, et al. Autosomal dominant vitreoretinochoroidopathy: when molecular genetic testing helps clinical diagnosis. Retina. 2019;39:867–78.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institutes of Health, National Eye Institute, Bethesda, MD, USA

    Catherine A. Cukras, Laryssa A. Huryn & Paul A. Sieving

  2. Department of Ophthalmology, School of Medicine, Davis, CA, USA

    Paul A. Sieving

  3. Center for Ocular Regenerative Therapy, University of California Davis, Davis, CA, USA

    Paul A. Sieving

Authors
  1. Catherine A. Cukras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laryssa A. Huryn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Sieving
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherine A. Cukras .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Oregon Health & Science University Department of Ophthalmology, Portland, OR, USA

    Daniel Albert

  2. Massachusetts Eye and Ear, Boston, MA, USA

    Joan Miller

  3. Department of Ophthalmology, University of Illinois at Chicago Department of Ophthalmology, Chicago, IL, USA

    Dimitri Azar

  4. Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    Lucy H. Young

Section Editor information

  1. Massachusetts Eye and Ear, Boston, USA

    Rachel Huckfeldt

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Cukras, C.A., Huryn, L.A., Sieving, P.A. (2021). Juvenile X-Linked Retinoschisis and Hereditary Vitreoretinopathies. In: Albert, D., Miller, J., Azar, D., Young, L.H. (eds) Albert and Jakobiec's Principles and Practice of Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-90495-5_5-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90495-5_5-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90495-5

  • Online ISBN: 978-3-319-90495-5

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation