Juvenile Retinoschisis

What is Juvenile Retinoschisis?

Juvenile retinoschisis is an inherited disease diagnosed in childhood that causes progressive loss of central and peripheral (side) vision due to degeneration of the retina.

What are the symptoms?

Juvenile retinoschisis, also known as X-linked retinoschisis, occurs almost exclusively in males. Although the condition begins at birth, symptoms do not typically become apparent until after the age of 10. About half of all patients diagnosed with juvenile retinoschisis first notice a decline in vision. Other early symptoms of the disease include an inability of both eyes to focus on an object (strabismus) and roving, involuntary eye movements (nystagmus).

Vision loss associated with juvenile retinoschisis is caused by the splitting of the retina into two layers. This retinal splitting most notably affects the macula, the central portion of the retina responsible for fine visual detail and color perception. On examination, the fovea (the center of the macula) has spoke-like streaks. The spaces created by the separated layers are often filled with blisters and ruptured blood vessels that can leak blood into the vitreous body (the transparent, colorless mass of jelly-like material filling the center of the eye). The presence of blood in the vitreous body causes further visual impairment. The vitreous body degenerates and may eventually separate from the retina. The entire retina may also separate from underlying tissue layers causing retinal detachments.

The extent and rate of vision loss vary greatly among patients with juvenile retinoschisis. Central vision is almost always affected. Peripheral (side) vision loss occurs in about half of all cases. Some patients retain useful vision well into adulthood, while others experience a rapid decline during childhood.

Is it an inherited disease?

Juvenile retinoschisis is genetically passed through families by the X-linked pattern of inheritance. In this type of inheritance, the gene for the disease is located on the X chromosome. Females have two X chromosomes and can carry the disease gene on one of their X chromosomes. Because they have a healthy version of the gene on their other X chromosome, carrier females typically are not affected by X-linked diseases such as juvenile retinoschisis. Sometimes, however, when carrier females are examined, the retina shows minor signs of the disease.

Males have only one X chromosome (paired with one Y chromosome) and are therefore genetically susceptible to X-linked diseases. Males cannot be carriers of X-linked diseases. Males affected with an X-linked disease always pass the gene on the X chromosome to their daughters, who then become carriers. Affected males never pass an X-linked disease gene to their sons because fathers pass the Y chromosome to their sons.

Female carriers have a 50 percent chance (or 1 chance in 2) of passing the X-linked disease gene to their daughters, who become carriers, and a 50 percent chance of passing the gene to their sons, who are then affected by the disease.

What treatment is available?

In 1997, researchers identified mutations in a gene on the X chromosome that cause juvenile retinoschisis. Scientists are now studying the gene to determine its function in the retina. This information will greatly enhance efforts to develop treatments for juvenile retinoschisis.

A recent study showed that a drug called dorzolamide may improve retinal health and restore some vision in people with retinoschisis.

Individuals with juvenile retinoschisis may also benefit from the use of low-vision aids, including electronic, computer-based and optical aids. Orientation and mobility training, adaptive training skills, job placement and income assistance are available through community resources.

Are there any other related diseases?

Juvenile retinoschisis can resemble other retinal degenerative diseases such as retinitis pigmentosa (RP), Goldman-Favre vitreoretinal dystrophy, Wagner's vitreoretinal dystrophy, and Sticklers syndrome. A thorough ophthalmologic examination, including diagnostic tests measuring retinal function and visual field, combined with an accurate documentation of family history, can distinguish between these diseases.

Causes progressive loss of vision

X-linked juvenile retinoschisis is a genetic disorder of the X chromosome. A gene identified as being responsible for juvenile retinoschisis, RS1, encodes an amino acid protein, retinoschisin, which is important in photoreceptor cells of the eye. Physical changes occur in the retina, the part of the eye responsible for vision. The retina splits into two layers, which impairs vision.

Since juvenile retinoschisis is an X-linked recessive disorder, it occurs primarily in boys (since they have only one X chromosome), but it can occur in females with two defective genes (one on each of their two X chromosomes). Juvenile retinoschisis occurs in individuals of all ethnic backgrounds.

Symptoms
Children with juvenile retinoschisis have gradually decreasing vision due to splitting of the retina.

Physical changes in the eye may include:

· development of cysts and ruptured blood vessels between the layers of the retina

· holes in the retinal layers, which may lead to detachment of the retina from its underlying tissue (5-22% of individuals)

· leakage of blood into the jelly-like material inside the eye (vitreous hemorrhage)

· changes in the macula, the area of clearest vision in the retina.

Individuals with juvenile retinoschisis may also have difficulty focusing on an object (strabismus) and roving, involuntary eye movements (nystagmus).

Diagnosis
Although juvenile retinoschisis may be diagnosed in infancy, most often it is found in a school-age boy who has failed to pass a school vision screening test. Since the loss of vision is gradual, a child may not be aware that he can’t see well. It is easy to miss the diagnosis in a young child. The extent and rate of vision loss vary greatly.

A thorough ophthalmological evaluation can help distinguish juvenile retinoschisis from similar retinal degenerative diseases such as retinitis pigmentosa. An imaging technique called optical coherence tomography (OCT) provides high-resolution cross-sectional images of the macula to look for abnormalities. OCT can show the changes present in juvenile retinoschisis. An electroretinogram will show dysfunction throughout the retina. Genetic testing can reveal the presence of the defective RS1 gene.

Treatment
No treatment is yet available to stop the progression of juvenile retinoschisis. Surgery can repair vitreous hemorrhage and retinal detachments. Low-vision aids, mobility training, and adaptive training skills can help individuals with vision loss. Genetic counseling can help identify family members who are carriers of the RS1 gene.

Research
Having identified a gene associated with X-linked juvenile retinoschisis, researchers are studying whether gene therapy can be use to replace the defective RS1 gene with an normal version. Experiments with mice have shown promising results. Research foundations such as "The Foundation Fighting Blindness" are working to identify other genes involved in juvenile retinoschisis and to develop therapies to treat the disease and prevent loss of vision.

AJ Whiting