Retinoblastoma is a malignant tumor (cancer) of the retina (part of the eye) that generally affects children under the age of 6. It is curable if detected early, but often requires surgical removal of the eye.

General information about Retinoblastoma

Retinoblastoma occurs when a cell of the growing retina develops a mutation in the RB gene (a tumor suppresser gene). This mutation causes the cell to grow out of control and become cancer. Sometimes this mutation develops in a child whose family has never had eye cancer, but other times the mutation is present in several family members. If the mutation runs in the family, there is a 50% chance that an affected person's children will also have the mutation and a high risk of developing retinoblastoma.

One or both eyes may be affected. A visible whiteness in the pupil may be present. Blindness can occur in the affected eye, and the eyes may appear crossed. The tumor can spread to the eye socket, and to the brain, by means of the optic nerve. This is a rare tumor, except in families that carry the RB gene mutation.

Causes of Retinoblastoma

The genetic cause of retinoblastoma has been extensively studied. It is described as a "two-hit" process. Normally, individuals have two good copies of the retinoblastoma gene (RB-1) on chromosome 13. The disease develops in individuals in which mutation has occurred in both copies of RB-1.

It appears that about 40% of patients are born with a defective copy (first "hit"), inherited from one parent. The second copy is rendered defective by a separate mutation (second "hit") that occurs in the eye. Individuals with an inherited RB-1 defect have high likelihood of developing retinoblastoma in both eyes. For these individuals, diagnosis occurs at age one. These patients also have increased risk of developing other types of cancer.

The other 60% of patients inherit two normal copies of RB-1 and develop the disease only after each copy experiences an independent mutation. The likelihood of two independent "hits" is lower, and these individuals are less likely to develop retinoblastoma in both eyes. For these individuals, average age of diagnosis is 2.1 years.

Chances of developing retinoblastoma decline sharply after age five. For those individuals who have had retinoblastoma in one eye, there is some possibility of the disease appearing in the other eye at any age into adulthood.

In cases with a family history of retinoblastoma, the child inherits a defective chromosome 13 from one parent. The defective alternative (allele) behaves dominantly, in that the victim needs only to inherit one defective gene. The tumor arises, however, only after a second, spontaneous mutation occurs in one of the cells of the retina; therefore, a situation then exists in which both copies of chromosome 13 carry defective alleles.

In the majority of cases, spontaneous mutations appear to occur in both copies of chromosome 13.

The RB-1 gene carries the information for making a protein called pRB. This protein regulates cell division. When pRB is absent or defective due to defective copies of the gene, uncontrolled cell division occurs, and cancer results. pRB appears to be involved in many types of cancer besides retinoblastoma.

Symptoms of Retinoblastoma

• A white glow in the eye that is often seen in photographs taken with a flash; instead of the typical "red eye" from the flash, the pupil may appear white or distorted
• Pupil, white spots
• Crossed eyes
• A red, painful eye
• Poor vision
• The iris may be a different color in each eye.

Diagnosis of Retinoblastoma

• An examination of the eye with dilation of the pupil
• A CT scan of the head to evaluate tumor and possible spread
• An ultrasound of the eye (head and eye echoencephalogram)

Treatment of Retinoblastoma

Treatment for retinoblastoma depends on the size and number of tumor locations (foci) in the eye, as well as whether the disease is found in one or both eyes.

When only one eye is involved, it is surgically removed (enucleated). If both eyes are involved, one eye can sometimes be saved by treating the tumor with radiation, photocoagulation (use of intense laser light to destroy cancer cells), or cryotherapy (use of intense cold to kill cancer cells). Chemotherapy is increasingly used as a follow-up to one of these treatments. However, some forms of radiation therapy have been shown to promote other cancers, especially of the bone.

Because many patients have a strong predisposition to this disease, frequent eye exams are recommended. Close monitoring is important. Even after successful treatment, retinoblastoma patients should receive frequent eye examinations in order to get the earliest possible warning if the disease recurs.