Skip to main content
SpringerLink
Log in

X-Linked Retinoschisis

  • Chapter
  • First Online:
Inherited Chorioretinal Dystrophies

Abstract

X-linked retinoschisis (XLRS) is an inherited vitreoretinal disorder associated with mutations in the RS1 gene located on Xp22 [40]. It was initially described by Haas in 1898 in two affected male patients who presented with the typical radiating cystic maculopathy [18]; an X-linked pattern of inheritance was first suggested by Pagenstecher in 1913 [30]. The term “retinoschisis” was first proposed by Wilczek in 1938 [48]. Since then, the disorder has been reported worldwide with an estimated incidence of between 1/5,000 and 1/20,000 [12]. There is a higher prevalence in Finland (about 1/14,000) due to three founder mutations [20]. The clinical manifestations are highly variable in affected males even within families. Female carriers generally have a normal eye examination, but may occasionally show subtle abnormalities. There have been a few reports of affected females with homozygous RS1 mutations in families with parental consanguinity [2, 39].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Alexander KR, Barnes CS, Fishman GA. High-frequency attenuation of the cone ERG and ON-response deficits in X-linked retinoschisis. Invest Ophthalmol Vis Sci. 2001;42:2094–101.

    CAS  PubMed  Google Scholar 

  2. Ali A, Feroze AH, Rizvi ZH, Rehman TU. Consanguineous marriage resulting in homozygous occurrence of X-linked retinoschisis in girls. Am J Ophthalmol. 2003;136:767–9.

    Article  PubMed  Google Scholar 

  3. Ando A, Takahashi K, Sho K, Matsushima M, Okamura A, Uyama M. Histopathological findings of X-linked retinoschisis with neovascular glaucoma. Graefes Arch Clin Exp Ophthalmol. 2000;238:1–7.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Audo I, Robson AG, Holder GE, Moore AT. The negative ERG: clinical phenotypes and disease mechanisms of inner retinal dysfunction. Surv Ophthalmol. 2008;53:16–40.

    Article  PubMed  Google Scholar 

  6. Bowles K, Cukras C, Turriff A, Sergeev Y, Vitale S, Bush RA, Sieving PA. 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 Central  PubMed  Google Scholar 

  7. Bradshaw K, George N, Moore A, Trump D. Mutations of the XLRS1 gene cause abnormalities of photoreceptor as well as inner retinal responses of the ERG. Doc Ophthalmol. 1999;98:153–73.

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Condon GP, Brownstein S, Wang NS, Kearns JA, Ewing CC. Congenital hereditary (juvenile X-linked) retinoschisis. Histopathologic and ultrastructural findings in three eyes. Arch Ophthalmol. 1986;104:576–83.

    Article  CAS  PubMed  Google Scholar 

  10. Gass JD. Nicotinic acid maculopathy. Am J Ophthalmol. 1973;76:500–10.

    Article  CAS  PubMed  Google Scholar 

  11. 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 

  12. George ND, Yates JR, Bradshaw K, Moore AT. Infantile presentation of X linked retinoschisis. Br J Ophthalmol. 1995;79:653–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Gerth C, Zawadzki RJ, Werner JS, Héon E. Retinal morphological changes of patients with X-linked retinoschisis evaluated by Fourier-domain optical coherence tomography. Arch Ophthalmol. 2008;126:807–11.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Ghajarnia M, Gorin MB. Acetazolamide in the treatment of X-linked retinoschisis maculopathy. Arch Ophthalmol. 2007;125:571–3.

    Article  PubMed  Google Scholar 

  15. Gieser EP, Falls HF. Hereditary retinoschisis. Am J Ophthalmol. 1961;51:1193–200.

    Article  CAS  PubMed  Google Scholar 

  16. Gregori NZ, Berrocal AM, Gregori G, Murray TG, Knighton RW, Flynn Jr HW, Dubovy S, Puliafito CA, Rosenfeld PJ. Macular spectral-domain optical coherence tomography in patients with X linked retinoschisis. Br J Ophthalmol. 2009;93:373–8.

    Article  CAS  PubMed  Google Scholar 

  17. Greven CM, Moreno RJ, Tasman W. Unusual manifestations of X-linked retinoschisis. Trans Am Ophthalmol Soc. 1990;88:211–25. discussion 226–218.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Haas J. Ueber das Zusammen vorkommen von Veranderungen der Retina und Choroidea. Arch Augenheilkd. 1898;37:343–8.

    Google Scholar 

  19. 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;85:238–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Huopaniemi L, Rantala A, Forsius H, Somer M, de la Chapelle A, Alitalo T. Three widespread founder mutations contribute to high incidence of X-linked juvenile retinoschisis in Finland. Eur J Hum Genet. 1999;7:368–76.

    Article  CAS  PubMed  Google Scholar 

  21. Janssen A, Min SH, Molday LL, Tanimoto N, Seeliger MW, Hauswirth WW, Molday RS, Weber BH. 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 

  22. 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 

  23. Khan NW, Jamison JA, Kemp JA, Sieving PA. Analysis of photoreceptor function and inner retinal activity in juvenile X-linked retinoschisis. Vision Res. 2001;41:3931–42.

    Article  CAS  PubMed  Google Scholar 

  24. Kim LS, Seiple W, Fishman GA, Szlyk JP. Multifocal ERG findings in carriers of X-linked retinoschisis. Doc Ophthalmol. 2007;114:21–6.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Lewis RA, Lee GB, Martonyi CL, Barnett JM, Falls HF. Familial foveal retinoschisis. Arch Ophthalmol. 1977;95:1190–6.

    Article  CAS  PubMed  Google Scholar 

  26. Manschot WA. Pathology of hereditary juvenile retinoschisis. Arch Ophthalmol. 1972;88:131–8.

    Article  CAS  PubMed  Google Scholar 

  27. Min SH, Molday LL, Seeliger MW, Dinculescu A, Timmers AM, Janssen A, Tonagel F, Tanimoto N, Weber BH, Molday RS, Hauswirth WW. Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol Ther. 2005;12:644–51.

    Article  CAS  PubMed  Google Scholar 

  28. Molday LL, Wu WW, Molday RS. Retinoschisin (RS1), the protein encoded by the X-linked retinoschisis gene, is anchored to the surface of retinal photoreceptor and bipolar cells through its interactions with a Na/K ATPase-SARM1 complex. J Biol Chem. 2007;282:32792–801.

    Article  CAS  PubMed  Google Scholar 

  29. 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  PubMed Central  CAS  PubMed  Google Scholar 

  30. Pagenstecher HE. Ueber eine unter dem Bilde der Natzhauterblosung verlaufende, erbliche Erkrankung der Retina. Graefes Arch Ophthalmol. 1913;86:457–62.

    Article  Google Scholar 

  31. Peachey NS, Fishman GA, Derlacki DJ, Brigell MG. Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis. Arch Ophthalmol. 1987;105:513–6.

    Article  CAS  PubMed  Google Scholar 

  32. Pearson R, Jagger J. Sex linked juvenile retinoschisis with optic disc and peripheral retinal neovascularisation. Br J Ophthalmol. 1989;73:311–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Reid SN, Akhmedov NB, Piriev NI, Kozak CA, Danciger M, Farber DB. The mouse X-linked juvenile retinoschisis cDNA: expression in photoreceptors. Gene. 1999;227:257–66.

    Article  CAS  PubMed  Google Scholar 

  34. Renner AB, Kellner U, Fiebig B, Cropp E, Foerster MH, Weber BH. ERG variability in X-linked congenital retinoschisis patients with mutations in the RS1 gene and the diagnostic importance of fundus autofluorescence and OCT. Doc Ophthalmol. 2008;116:97–109.

    Article  PubMed  Google Scholar 

  35. Retinoschisis consortium. Functional implication of the spectrum of mutations found in 234 cases of X-linked juvenile retinoschisis. Hum Mol Genet. 1998;7:1185–92.

    Article  Google Scholar 

  36. Robson AG, Mengher LS, Tan MH, Moore AT. An unusual fundus phenotype of inner retinal sheen in X-linked retinoschisis. Eye (Lond). 2009;23:1876–8.

    Article  CAS  Google Scholar 

  37. Rodríguez FJ, Rodríguez A, Mendoza-Londoño R, Tamayo ML. X-linked retinoschisis in three females from the same family: a phenotype-genotype correlation. Retina. 2005;25:69–74.

    Article  PubMed  Google Scholar 

  38. Rosenfeld PJ, Flynn Jr HW, McDonald HR, Rubsamen PE, Smiddy WE, Sipperley JO, Boniuk I, Packer AJ. Outcomes of vitreoretinal surgery in patients with X-linked retinoschisis. Ophthalmic Surg Lasers. 1998;29:190–7.

    CAS  PubMed  Google Scholar 

  39. Saleheen D, Ali A, Khanum S, Ozair MZ, Zaidi M, Sethi MJ, Khan N, Frossard P. Molecular analysis of the XLRS1 gene in 4 females affected with X-linked juvenile retinoschisis. Can J Ophthalmol. 2008;43:596–9.

    Article  PubMed  Google Scholar 

  40. Sauer CG, Gehrig A, Warneke-Wittstock R, Marquardt A, Ewing CC, Gibson A, Lorenz B, Jurklies B, Weber BH. Positional cloning of the gene associated with X-linked juvenile retinoschisis. Nat Genet. 1997;17:164–70.

    Article  CAS  PubMed  Google Scholar 

  41. 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  PubMed Central  CAS  PubMed  Google Scholar 

  42. Shinoda K, Ohde H, Mashima Y, Inoue R, Ishida S, Inoue M, Kawashima S, Oguchi Y. On- and off-responses of the photopic electroretinograms in X-linked juvenile retinoschisis. Am J Ophthalmol. 2001;131:489–94.

    Article  CAS  PubMed  Google Scholar 

  43. Takada Y, Fariss RN, Muller M, Bush RA, Rushing EJ, Sieving PA. Retinoschisin expression and localization in rodent and human pineal and consequences of mouse RS1 gene knockout. Mol Vis. 2006;12:1108–16.

    CAS  PubMed  Google Scholar 

  44. Takada Y, Vijayasarathy C, Zeng Y, Kjellstrom S, Bush RA, Sieving PA. Synaptic pathology in retinoschisis knockout (Rs1-/y) mouse retina and modification by rAAV-Rs1 gene delivery. Invest Ophthalmol Vis Sci. 2008;49:3677–86.

    Article  PubMed Central  PubMed  Google Scholar 

  45. 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. 2011;31:312–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Tsang SH, Vaclavik V, Bird AC, Robson AG, Holder GE. Novel phenotypic and genotypic findings in X-linked retinoschisis. Arch Ophthalmol. 2007;125:259–67.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. van Schooneveld MJ, Miyake Y. Fundus albipunctatus-like lesions in juvenile retinoschisis. Br J Ophthalmol. 1994;78:659–61.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Wilczek M. Ein der netzhautspaltung (retinoschisi) mit einer offnung. Zeit Augenhlkd. 1935;85:108–16.

    Google Scholar 

  49. Wu G, Cotlier E, Brodie S. A carrier state of X-linked juvenile retinoschisis. Ophthalmic Paediatr Genet. 1985;5:13–7.

    Article  CAS  PubMed  Google Scholar 

  50. Yanoff M, Kertesz Rahn E, Zimmerman LE. Histopathology of juvenile retinoschisis. Arch Ophthalmol. 1968;79(1):49–53.

    Article  CAS  PubMed  Google Scholar 

  51. Yassur Y, Nissenkorn I, Ben-Sira I, Kaffe S, Goodman RM. Autosomal dominant inheritance of retinoschisis. Am J Ophthal. 1982;94:338–43.

    Article  CAS  PubMed  Google Scholar 

  52. Yu J, Ni Y, Keane PA, Jiang C, Wang W, Xu G. Foveomacular schisis in juvenile X-linked retinoschisis: an optical coherence tomography study. Am J Ophthalmol. 2010;149:973–8.

    Article  PubMed  Google Scholar 

  53. Zeng Y, Takada Y, Kjellstrom S, Hiriyanna K, Tanikawa A, Wawrousek E, Smaoui N, Caruso R, Bush RA, Sieving PA. RS-1 gene delivery to an adult Rs1h knockout mouse model restores ERG b-wave with reversal of the electronegative waveform of X-linked retinoschisis. Invest Ophthalmol Vis Sci. 2004;45:3279–85.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM, U968, Paris, 75012, France

    Isabelle Audo, Saddek Mohand-Saïd & José-Alain Sahel

  2. CNRS, UMR_7210, Paris, 75012, France

    Isabelle Audo, Saddek Mohand-Saïd & José-Alain Sahel

  3. Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, 75012, France

    Isabelle Audo, Saddek Mohand-Saïd & José-Alain Sahel

  4. Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 1423, Paris, 75012, France

    Isabelle Audo, Saddek Mohand-Saïd & José-Alain Sahel

  5. Department of Electrophysiology, Moorfields Eye Hospital, City Road, London, EC1V 2PD, UK

    Graham E. Holder & Anthony T. Moore

  6. UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK

    Graham E. Holder & Anthony T. Moore

Authors
  1. Isabelle Audo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saddek Mohand-Saïd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José-Alain Sahel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Graham E. Holder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony T. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabelle Audo .

Editor information

Editors and Affiliations

  1. Service d’Exploration de la Vision et Neuro-ophtalmologie, Centre Hospitalier Universitaire de Lille, Hôpital Roger Salengro, Lille Cedex, France

    Bernard Puech

  2. Department of Ophthalmology, Ghent University Hospital, Ghent University, Ghent, Belgium

    Jean-Jacques De Laey

  3. Department of Electrophysiology, Moorfields Eye Hospital, London, United Kingdom

    Graham E. Holder

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Audo, I., Mohand-Saïd, S., Sahel, JA., Holder, G.E., Moore, A.T. (2014). X-Linked Retinoschisis. In: Puech, B., De Laey, JJ., Holder, G. (eds) Inherited Chorioretinal Dystrophies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69466-3_42

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-69466-3_42

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-69464-9

  • Online ISBN: 978-3-540-69466-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation