Background

In 1898, Haas first described X-linked juvenile retinoschisis (XLRS). This condition is also known as congenital retinoschisis, vitreous veils, congenital vascular veils in the vitreous, and congenital cystic retinal detachment; however, Jaeger introduced the term retinoschisis in 1953.

An example of juvenile retinoschisis is shown in the image below.

Fundus photograph of juvenile retinoschisis demonstrating stellate spokelike appearance with microcysts.

View Media Gallery

Pathophysiology

Using positional cloning, Sauer and associates identified XLRS1, the gene responsible for X-linked juvenile retinoschisis.^[1]XLRS1 is located on band Xp22.2. XLRS1 encodes a 224 amino acid protein retinoschisin that is expressed in photoreceptor and bipolar cells. Retinoschisin is a secreted protein that is involved in cellular adhesion and cell-cell interactions within the inner nuclear layer as well as synaptic connection between photoreceptors and bipolar cells. Defective or absent retinoschisin may reduce adhesion of the retinal layers, resulting in the creation of schisis cavities.

Frequency

United States

Prevalence of X-linked juvenile retinoschisis ranges from 1 case per 5,000 population to 1 case per 25,000 population.

International

The highest prevalence has been reported in Finland. X-linked juvenile retinoschisis has also been reported in Indonesian, Chinese, Japanese, Indian, and Portuguese families.

Mortality/Morbidity

Early in life, the central vision usually is mildly impaired because of a cyst in the fovea. Later, the central vision can become impaired more markedly, resulting in symptoms similar to those of macular degeneration. More seriously, retinal detachments can occur when holes in the inner and outer retinal layers are present. The incidence rate is 5-22% of individuals affected. X-linked juvenile retinoschisis is the most common cause of vitreous hemorrhage in young boys.^[2]Other complications include neovascular glaucoma, vitreoretinal traction with secondary macular dragging, and secondary optic atrophy.

Race

This condition has been reported in whites, Cherokee Indians, and blacks.

Sex

Although this disease is primarily seen in males, a homozygous woman from a consanguineous marriage can also be affected. The daughters of males with X-linked juvenile retinoschisis are obligate carriers, whereas the sons are spared. No male-to-male transmission should be seen in families with this disease. Male offspring of two carriers have a 50% chance of being affected; female offspring have a 50% chance of being a carrier. Some cases can seem sporadic because other males in the family may be affected so mildly that they have never been diagnosed.

Age

Patients have been diagnosed as early as age 3 months; however, most patients are seen at 5 years or older. They are typically referred when they fail to pass a school vision screening test. X-linked juvenile retinoschisis often presents in a young boy with slightly decreased vision that cannot be corrected fully by refraction. Diagnosis is easily missed during early onset.

Prognosis

With prompt identification and management of individuals with X-linked juvenile retinoschisis, the vision should be adequately preserved.

Patient Education

Educating the patient and the family members on the symptoms of vitreous hemorrhage and retinal detachment can result in prompt detection and management of these events that can threaten central vision.

Genetic counseling has become an important conversation for these patients and their family members.

Clinical Presentation

Sauer CG, Gehrig A, Warneke-Wittstock R, et al. Positional cloning of the gene associated with X-linked juvenile retinoschisis. Nat Genet. 1997 Oct. 17(2):164-70. [QxMD MEDLINE Link].
Lee JJ, Kim JH, Kim SY, Park SS, Yu YS. Infantile vitreous hemorrhage as the initial presentation of X-linked juvenile retinoschisis. Korean J Ophthalmol. 2009 Jun. 23(2):118-20. [QxMD MEDLINE Link]. [Full Text].
Sikkink SK, Biswas S, Parry NR, Stanga PE, Trump D. X-linked retinoschisis: an update. J Med Genet. 2007 Apr. 44 (4):225-32. [QxMD MEDLINE Link].
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 Feb. 128(2):190-7. [QxMD MEDLINE Link].
Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May. 31 (3):195-212. [QxMD MEDLINE Link].
Apushkin MA, Fishman GA. Use of dorzolamide for patients with X-linked retinoschisis. Retina. 2006 Sep. 26(7):741-5. [QxMD MEDLINE Link].
Apushkin MA, Fishman GA, Rajagopalan AS. Fundus findings and longitudinal study of visual acuity loss in patients with X-linked retinoschisis. Retina. 2005 Jul-Aug. 25(5):612-8. [QxMD MEDLINE Link].
Bergen AA, ten Brink JB, van Schooneveld MJ. Efficient DNA carrier detection in X linked juvenile retinoschisis. Br J Ophthalmol. 1995 Jul. 79(7):683-6. [QxMD MEDLINE Link].
Brucker AJ, Spaide RF, Gross N, Klancnik J, Noble K. Optical coherence tomography of X-linked retinoschisis. Retina. 2004 Feb. 24(1):151-2. [QxMD MEDLINE Link].
Dahl N, Pettersson U. Use of linked DNA probes for carrier detection and diagnosis of X-linked juvenile retinoschisis. Arch Ophthalmol. 1988 Oct. 106(10):1414-6. [QxMD MEDLINE Link].
Forsius HJ, Vainio-Mattila B, Erikson A. X-linked hereditary retinoschisis. Br J Ophthalmol. 1962. 46:678-681.
Gao H, Kusumi R, Yung CW. Optical coherence tomographic findings in X-linked juvenile retinoschisis. Arch Ophthalmol. 2005 Jul. 123(7):1006-8. [QxMD MEDLINE Link].
Gehrig AE, Warneke-Wittstock R, Sauer CG, Weber BH. Isolation and characterization of the murine X-linked juvenile retinoschisis (Rs1h) gene. Mamm Genome. 1999 Mar. 10(3):303-7. [QxMD MEDLINE Link].
Ghajarnia M, Gorin MB. Acetazolamide in the treatment of X-linked retinoschisis maculopathy. Arch Ophthalmol. 2007 Apr. 125(4):571-3. [QxMD MEDLINE Link].
Greene JM, Shakin EP. Optical coherence tomography findings in foveal schisis. Arch Ophthalmol. 2004 Jul. 122(7):1066-7. [QxMD MEDLINE Link].
Helve J. Colour vision in X-chromosomal juvenile retinoschisis. Mod Probl Ophthal. 1971. 11:122-129.
Ide CH, Wilson RJ. Juvenile retinoschisis. Br J Ophthalmol. 1973 Aug. 57(8):560-2. [QxMD MEDLINE Link].
Joshi MM, Drenser K, Hartzer M, Dailey W, Capone A Jr, Trese MT. Intraschisis cavity fluid composition in congenital X-linked retinoschisis. Retina. 2006 Sep. 26(7 Suppl):S57-60. [QxMD MEDLINE Link].
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 Aug. 48(8):3837-45. [QxMD MEDLINE Link].
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. 13:804-12. [QxMD MEDLINE Link].
Manschot WA. Pathology of hereditary juvenile retinoschisis. Arch Ophthalmol. 1972 Aug. 88(2):131-8. [QxMD MEDLINE Link].
McMahon TT, Rosenthal BP. X-linked juvenile retinoschisis. J Am Optom Assoc. 1983 Jan. 54(1):55-61. [QxMD MEDLINE Link].
Min SH, Molday LL, Seeliger MW, et al. Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol Ther. 2005 Oct. 12(4):644-51. [QxMD MEDLINE Link].
Molday LL, Hicks D, Sauer CG, Weber BH, Molday RS. Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells. Invest Ophthalmol Vis Sci. 2001 Mar. 42(3):816-25. [QxMD MEDLINE Link].
Pawar H, Bingham EL, Hiriyanna K, Segal M, Richards JE, Sieving PA. X-linked juvenile retinoschisis: localization between (DXS1195, DXS418) and AFM291wf5 on a single YAC. Hum Hered. 1996 Nov-Dec. 46(6):329-35. [QxMD MEDLINE Link].
Peachey NS, Fishman GA, Derlacki DJ, Brigell MG. Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis. Arch Ophthalmol. 1987 Apr. 105(4):513-6. [QxMD MEDLINE Link].
Regillo CD, Custis PH. Surgical management of retinoschisis. Curr Opin Ophthalmol. 1997 Jun. 8(3):80-6. [QxMD MEDLINE Link].
Reid SN, Yamashita C, Farber DB. Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells. J Neurosci. 2003 Jul 9. 23(14):6030-40. [QxMD MEDLINE Link].
Sabates FN. Juvenile retinoschisis. Am J Ophthalmol. 1966 Oct. 62(4):683-8. [QxMD MEDLINE Link].
Shastry BS, Hejtmancik FJ, Margherio RT, Trese MT. Linkage mapping of new X-linked juvenile retinoschisis kindreds using microsatellite markers. Biochem Biophys Res Commun. 1996 Mar 27. 220(3):824-7. [QxMD MEDLINE Link].
Shimazaki J, Matsuhashi M. Familial retinoschisis in female patients. Doc Ophthalmol. 1987 Mar. 65(3):393-400. [QxMD MEDLINE Link].
Souied EH, Goritsa A, Querques G, Coscas G, Soubrane G. Indocyanine green angiography of juvenile X-linked retinoschisis. Am J Ophthalmol. 2005 Sep. 140(3):558-61. [QxMD MEDLINE Link].
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. 13:611-7. [QxMD MEDLINE Link].
Tantri A, Vrabec TR, Cu-Unjieng A, Frost A, Annesley WH Jr, Donoso LA. X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol. 2004 Mar-Apr. 49(2):214-30. [QxMD MEDLINE Link].
Teixeira C, Rocha-Sousa A, Trump D, Brandao E, Falcao-Reis F. Identification of XLRS1 gene mutation (608C > T) in a Portuguese family with juvenile retinoschisis. Eur J Ophthalmol. 2005 Sep-Oct. 15(5):638-40. [QxMD MEDLINE Link].
The Retinoschisis Consortium. Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis. Hum Mol Genet. 1998 Jul. 7(7):1185-92. [QxMD MEDLINE Link].
Trese MT, Ferrone PJ. The role of inner wall retinectomy in the management of juvenile retinoschisis. Graefes Arch Clin Exp Ophthalmol. 1995 Nov. 233(11):706-8. [QxMD MEDLINE Link].
Verdaguer J. Juvenile retinal detachment. Pan American Association of Ophthalmology and American Journal of Ophthalmology Lecture. Am J Ophthalmol. 1982 Feb. 93(2):145-56. [QxMD MEDLINE Link].
Wu G, Cotlier E, Brodie S. A carrier state of X-linked juvenile retinoschisis. Ophthalmic Paediatr Genet. 1985 Feb. 5(1-2):13-7. [QxMD MEDLINE Link].
Wu WW, Molday RS. Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis. J Biol Chem. 2003 Jul 25. 278(30):28139-46. [QxMD MEDLINE Link].
Yanoff M, Kertesz Rahn E, Zimmerman LE. Histopathology of juvenile retinoschisis. Arch Ophthalmol. 1968 Jan. 79(1):49-53. [QxMD MEDLINE Link].
Yassur Y, Nissenkorn I, Ben-Sira I, Kaffe S, Goodman RM. Autosomal dominant inheritance of retinoschisis. Am J Ophthalmol. 1982 Sep. 94(3):338-43. [QxMD MEDLINE Link].
Zeng Y, Takada Y, Kjellstrom S, et al. 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 Sep. 45(9):3279-85. [QxMD MEDLINE Link].
Alitalo T, Kruse TA, de la Chapelle A. Refined localization of the gene causing X-linked juvenile retinoschisis. Genomics. 1991 Mar. 9(3):505-10. [QxMD MEDLINE Link].
Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May. 31(3):195-212. [QxMD MEDLINE Link].
Delgado D, del Pozo-Rodriguez A, Solinis MA, et al. Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis. Hum Gene Ther. 2012 Apr. 23(4):345-55. [QxMD MEDLINE Link].
Byrne LC, Oztürk BE, Lee T, Fortuny C, Visel M, Dalkara D, et al. Retinoschisin gene therapy in photoreceptors, Müller glia or all retinal cells in the Rs1h-/- mouse. Gene Ther. 2014 Jun. 21(6):585-92. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Electroretinogram of a patient with juvenile retinoschisis.
Fundus photograph of juvenile retinoschisis demonstrating stellate spokelike appearance with microcysts.

of 2

Author

Leslie Small, OD Optometrist

Leslie Small, OD is a member of the following medical societies: American Optometric Association

Disclosure: Nothing to disclose.

Coauthor(s)

Kent W Small, MD Director/President, Macula and Retina Institute; President, Molecular Insight, LLC; Consulting Surgeon, Glendale Eye Medical Group

Kent W Small, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for Physician Leadership, American Association for the Advancement of Science, American Medical Association, American Medical Informatics Association, American Ophthalmological Society, American Society of Human Genetics, Association for Research in Vision and Ophthalmology, California Medical Association, Macula Society, Retina Society, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Steve Charles, MD Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine

Disclosure: Received royalty and consulting fees for: Alcon Laboratories.

Chief Editor

Donny W Suh, MD, MBA, FAAP, FACS Professor, Department of Ophthalmology, Chief of Pediatric Ophthalmology and Adult Strabismus, Medical Director of Eye-Mobile, Gavin Herbert Eye Institute, UC Irvine Health, University of California, Irvine, School of Medicine; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Chief Medical Officer, Suh Precision Syringe, LLC; Medical Staff, Children’s Hospital of Orange County

Donny W Suh, MD, MBA, FAAP, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus, American College of Healthcare Executives, American College of Surgeons, American Medical Association, Section on Ophthalmology, American Ophthalmological Society, International Strabismological Association, Iowa Medical Society, Metro Omaha Medical Society, National Eye Care Project, Nebraska Chapter of American Academy of Pediatrics, ORBIS, Surgical Eye Expeditions (SEE) International

Disclosure: Received research grant from: NIH / PEDIG.

Additional Contributors

Russell P Jayne, MD Vitreoretinal Surgeon, The Retina Center at Las Vegas

Russell P Jayne, MD is a member of the following medical societies: American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Retina Specialists

Disclosure: Nothing to disclose.

Colleen M McLellan Mills College, Oakland, California

Disclosure: Nothing to disclose.

Acknowledgements

Mi-Kyoung Song, MD Vitreoretinal Surgeon, Eye Associates of New Mexico

Mi-Kyoung Song, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Retina Specialists, and New Mexico Medical Society

Disclosure: Nothing to disclose.