NORD gratefully acknowledges Lindsay Renz, Editorial Intern from the University of Notre Dame, and Amy Turriff, MS, genetic counselor, National Eye Institute, Ophthalmic Genetics and Visual Function Branch, National Institutes of Health, for assistance in the preparation of this report.
X-linked retinoschisis (XLRS) is a genetic condition affecting boys and men. It is typically diagnosed in childhood, in some cases as early as three months of age. The main symptom is reduced vision that cannot be improved with glasses. While some people with XLRS may experience progressive vision loss throughout their life, other people may have relatively stable vision throughout their lifetime. XLRS is caused by mutations in a gene on the X chromosome called RS1 which encodes a protein called retinoschisin. This protein is important for the development and maintenance of the retina (the tissue lining the back of the eye). Without normal retinoschisin protein, the layers of the retina split (“schisis”), inter-cell communication is disrupted and vision is lost.
The main symptom of XLRS is reduced visual acuity. While variable, vision is typically in the 20/60 to 20/120 range. Some people with XLRS experience retinal detachment or bleeding within the eye.
The natural history of XLRS is still not entirely understood. Classically, it has been described as progressive in childhood, plateauing, then progressive in later adulthood. However, this has not been observed in the reviewer’s experience. In uncomplicated cases, visual prognosis is good and there can be very little progression in a person’s lifetime. Most patients with XLRS never reach the point of legal blindness.
XLRS is caused by a change (mutation) in a gene. Genes provide information and instruction to make proteins, much like a blueprint. Proteins are the building blocks of cells and allow cells to have their unique functions.
XLRS is caused by mutations in a gene on the X chromosome called RS1.
XLRS is inherited as an X-linked trait. Men only have one X chromosome, whereas women have two. Women who have an abnormal RS1 gene “carry” the condition, but do not have any vision problems associated with XLRS since they almost always have a second normal RS1 gene. Men who have an abnormal RS1 gene have symptoms of XLRS. Women who are carriers have a 50% chance of passing on their abnormal RS1 gene to each of their children. When passed to a daughter, the daughter will also be a carrier for XLRS. When passed to a son, the son will have XLRS. When men with XLRS have children, all of their daughters will be carriers and none of their sons will have XLRS.
Diagnosis of XLRS is made by eye examination using various testing modalities. Individuals have reduced vision, schisis that can be seen on examination and imaging, and abnormal electroretinograms (a test that assesses the function of the retina) in most cases. Some individuals also have a family history consistent with X-linked inheritance. Molecular genetic testing for mutations in the RS1 gene is available to confirm the diagnosis.
Treatment is generally symptomatic and supportive. Low-vision aids such as large-print textbooks; preferential seating in the front of the classroom; and use of handouts with high contrast can be useful. Treatment of retinoschisis may require the care of a retinal surgeon to address the infrequent complications of vitreous hemorrhage (bleeding in the eye) and retinal detachment. Affected boys and men are recommended to avoid activities such as contact sports, which may pose an increased risk for retinal detachment.
Genetic counseling is recommended for boys and men with XLRS and their families.
There are now ongoing early-phase clinical trials evaluating the safety and effectiveness of gene transfer (also known as gene therapy) in adults with XLRS.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/
For information about clinical trials conducted in Europe, contact:
Haivala DH, Nanda SK. X-Linked Juvenile Retinoschisis. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:662.
Tantri A, Vrabee TR, Cu-Unjieng A, et al. X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol. 2004;49:214-30.
Musarella MA. Molecular genetics of macular degeneration. Doc Ophthalmol. 2001;102:165-77.
Apushkin MA, Fishman GA, Janowicz MJ. Correlation of optical coherence tomography findings with visual acuity and macular lesions in patients with X-linked juvenile retinoschisis. Ophthalmology. 2005;112:495-501.
Rodriguez FJ, Rodriguez A, Mendoza-Londono R, et al. X-lined retinoschisis in three females from the same family: a phenotype-genotype correlation. Retina. 2005;25:69-74.
Eriksson U, Larsson E, Holmstrom G. Optical coherence tomography in the diagnosis of X-linked juvenile retinoschisis. Acta Ophthalmol Scand. 2004;82:218-23.
Piao CH, Kondo M, Nakamura M, et al. Multifocal electroretinograms in X-linked retinoschisis. Invest Ophthalmol Vis Sci. 2003;44:4920-30.
Huang S, Wu D, Jiang F, et al. The multifocal electroretinogram in X-linked juvenile retinoschisis. Doc Ophthalmol. 2003;106:251-55.
Sieving PA, MacDonald IM, Chan S. X-Linked Juvenile Retinoschisis. 2003 Oct 24 [Updated 2014 Aug 28]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1222/ Accessed October 18, 2016.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Retinoschisis 1, X-Linked, Juvenile; RS1. Entry Number; 312700. Available at http://omim.org/entry/312700 Last Edit Date 07/07/2016. Accessed October 18, 2016.
Small KW. Retinoschisis, Juvenile.Medscape. Updated: Aug 26, 2014. http://emedicine.medscape.com/article/1225857-overview Accessed October 18, 2016.
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