This study will explore the causes and eye problems of X-linked juvenile retinoschisis (XLRS), an inherited disease that causes vision loss primarily in young males. The vision loss, which worsens over time, is a result of schisis, or splitting, of the layers of the retina (tissue that lines the back of the eye). A better understanding of why and how XLRS develops might lead to improved treatments.

Patients 9 months of age and older with XLRS and females who are suspected carriers of the gene responsible for the disease (such as the mother of the patient) may be eligible for this study. Other family members of patients also may be enrolled.

Patients will undergo the following tests and procedures:

• Personal and family medical history to review past and current medical conditions and treatments, particularly regarding eye disease, and to construct a family tree.
• Eye examination to assess visual acuity (eye chart test) and examine pupils, lens, retina, and eye movements. The pupils will be dilated with drops for this examination.
• Photography of the retina to help evaluate the status of the retina.
• Specialized eye tests to evaluate color vision, field of vision, and ability to see in the dark.
• Electroretinogram (ERG) to examine what happens to the eyes after a flash of bright light. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops and contact lenses are placed on the eyes. The patient looks inside a large empty bowl and then a light flashes, first in the dark and then with a light turned on inside the bowl. The contact lenses sense small electrical signals generated by the retina when the light flashes.
• Blood test to examine DNA for genetic study of XLRS.

Family members will provide a blood sample for genetic study.

Juvenile retinoschisis is an X-linked disease of retinal development caused by mutations in the XLRS1 gene. A rare condition, affecting 1:5000 to 1:25000 males worldwide, the disease is one of the more common causes of juvenile macular degeneration affecting boys. Affected individuals generally present with vision loss in early grade school. Schisis (splitting) of the nerve fiber layer is often seen clinically as a wheel like cystic formation in the macula in young patients. Peripheral schisis is reported in about 50% of the patients, predominantly in the inferotemporal part of the retina. Visual deterioration often progresses during the first 1 or 2 decades of life. The disease is mainly stable after puberty with slow progression continuing until the fifth or sixth decade. By the age of 40 to 50 years, macular degeneration often occurs, causing additional visual failure. In patients over 50 years of age macular pigmentary changes and retinal pigment epithelial (RPE) atrophy are common.

The objectives of this registry are to understand the nature of the XLRS disease in order to develop appropriate treatments by characterizing the anatomical and functional characteristics of retinoschisis and ultimately generate a well-documented genotype-phenotype correlation map. A minimum of 100 males diagnosed with X-linked retinoschisis will undergo clinical examination and have their blood drawn for genotyping. Blood will also be drawn from available and consenting mothers of affected males. An eye examination will be performed and blood drawn from any symptomatic available and consenting female family members. A maximum of 500 affected males and family members may be enrolled. Sites outside of NIH are participating as referral centers to accumulate the cohort.

• 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 Aug;128(2):179-84.
• Eksandh LC, Ponjavic V, Ayyagari R, Bingham EL, Hiriyanna KT, Andreasson S, Ehinger B, Sieving PA. Phenotypic expression of juvenile X-linked retinoschisis in Swedish families with different mutations in the XLRS1 gene. Arch Ophthalmol. 2000 Aug;118(8):1098-104.
• George ND, Yates JR, Moore AT. X linked retinoschisis. Br J Ophthalmol. 1995 Jul;79(7):697-702. Review. No abstract available.

• INCLUSION CRITERIA:

Eligible participants must satisfy one of the criteria below.

1. Males diagnosed with X-Linked Juvenile Retinoschisis (proband); or
2. Females who are suspected carriers (i.e., mother of proband); or

3. Other unaffected relatives of probands, including both males and females.

   EXCLUSION CRITERIA:

   Affected males will be ineligible for participation if:

4. They have significant media opacities or other obstructions precluding a complete fundus examination including photography in all affected eyes.

5. Are unable to cooperate with examination procedures without anesthesia

   Both affected and unaffected individuals will be ineligible for participation if:

6. They are unwilling or unable to contribute a blood sample for genotyping.
7. They are unable to provide their own consent, if an adult
8. Are younger than 2 years (seen at the NIH) or younger than 9 months (participating offsite through medical record review and blood submission)
9. Are unable to cooperate with study procedures without anesthesia.