Retinoblastoma: The Basics

What is Retinoblastoma?

The retinoblastoma gene is a type of gene known as a "tumor suppressor gene." Tumor suppressor genes act as a "brake" on cell division. The retinoblastoma gene is present in all cells of the body. If an unwanted mutation forms in one of the cells of the body, the retinoblastoma protein (also known as pRB) acts as a brake to prevent that mutant cell from dividing. However, if the retinoblastoma gene is damaged (mutated), a defective pRB may be produced and the cell can then divide unchecked, leading to cancer.

Retinoblastoma arises from the retina of the eye; it affects one eye in approximately 75% of cases, and both eyes in 25% of cases. It causes a tumor to form within the eye, which can then grow and destroy the internal structures of the eye. It can also spread to other areas such as the eye socket, brain, lungs, and bones. However, retinoblastoma is generally limited to the eye, and 90% of children who develop retinoblastoma are cured.

Retinoblastoma is the most common childhood cancer involving the eye. Having said that, it is still relatively uncommon among all childhood cancers, making up about 3% of all childhood cancers in children less than 15 years old. It is diagnosed in about 4 out of every million children per year. Although retinoblastoma can be diagnosed at any age, most children are diagnosed before the age of 2, and about 95% of cases are diagnosed in children younger than 5 years of age.

Retinoblastoma is thought to occur based on the "two-hit" hypothesis. There are two copies of the retinoblastoma gene in each cell, and in order for retinoblastoma to occur, both copies of this gene need to be defective. There are two patterns of retinoblastoma that can occur: an inheritable, or germline form (40% of cases), and a sporadic form (60% of cases). There are two ways that the inheritable form can occur. One way is through direct inheritance of one defective gene from a parent, which causes about 25% of the inheritable cases of the disease. This also means that one parent is a "carrier" of the defective gene. However, if the parent never developed a second retinoblastoma mutation, he or she would have never manifested any symptoms of the disease. Hence, there may not be a family history, even though one of the parents is a carrier, and indeed less than 10% of children diagnosed with retinoblastoma have a family history of the disease. The second way is through a germline mutation of one copy of the retinoblastoma gene, which causes about 75% of the inheritable form of the disease. A germline mutation occurs when the retinoblastoma gene is mutated during conception, and this new mutation can then affect all cells in the body. Hence, all children with the inheritable form of retinoblastoma already have one defective retinoblastoma gene, and only one additional mutation is required to cause the disease. In the sporadic form of the disease, the child does not inherit a defective copy of the gene, and thus in order for the child to develop the disease, two "hits" are required to cause defects in the two normal copies of the retinoblastoma gene.

The inheritable and sporadic forms of retinoblastoma also manifest themselves in different fashions. Either form of retinoblastoma can affect just one eye. However, only the inheritable form of retinoblastoma can cause disease in both eyes. The inheritable form of the disease causes tumors in one eye about 15% of the time, tends to occur at an earlier age, and is associated with multiple tumors in the eye. As the inheritable form tends to occur in younger children, infants presenting with one or both eyes affected most likely have the inheritable form of the disease. Studies have found that people who are diagnosed with the inheritable form of retinoblastoma are at increased risk for developing secondary cancers.

Studies have shown that within 50 years of diagnosis, approximately 51% of people with the inheritable form and 5% of those with the sporadic form of retinoblastoma will develop another cancer. Radiation treatment affects the rate of secondary cancer development in children with the inheritable form of retinoblastoma. Approximately 58% of children who received radiation developed secondary cancers, compared to 26.5% of children who did not receive radiation therapy. However, these studies were based on older radiation techniques, and it appears that this risk is reduced in children treated with lower doses of radiation and at ages greater than 1 year. Even in children who were spared radiation, there was an increased risk of death from several types of cancer in children with the inheritable form of retinoblastoma. These cancers included bladder, lung, and epithelial cancers (cancers of the lining of intestines and the lining of the body cavities). It also appears that people with the inheritable form of retinoblastoma are at increased risk for developing bone, soft tissue, and skin cancers. Hence, people who have the inheritable form of retinoblastoma should be carefully monitored for a second cancer for life. The general guideline for children with the inheritable form of retinoblastoma is to have routine examinations every 2 to 4 months for at least 28 months. For those who are treated, routine examinations should be performed until the child is 7 years of age.

Am I at Risk for Retinoblastoma?

This cancer appears to equally affect boys and girls as well as African Americans and Caucasians. The retinoblastoma gene is located on chromosome 13q. Children who have a parent or sibling with this disease or children with a known mutation of chromosome 13q are at increased risk for developing retinoblastoma. There is no way to correct or prevent these inheritable genetic defects at present. What causes the sporadic form of retinoblastoma is not well known at this time, and there are no specific recommendations regarding ways to prevent retinoblastoma.

It is also important to monitor for other cancers in children who have the inheritable form of retinoblastoma. Defective retinoblastoma gene is known to play an important role in other types of cancer, and children who have the inheritable form of retinoblastoma are at increased risk for several other types of tumors. These tumors include osteogenic sarcoma (bone tumors), soft tissue sarcomas, and melanomas. This risk is not seen to the same degree in people with the sporadic form of the disease. Tobacco use also appears to increase the risk of secondary cancers in people with the inheritable form of retinoblastoma and should be avoided.

How can I Prevent Retinoblastoma?

Unfortunately, aside from the genetic risk factors, the specific exposures or other conditions which lead to retinoblastoma are not well known. Hence, there are no good guidelines regarding how to best prevent retinoblastoma. However, for children who are known to have a family history of retinoblastoma, frequent follow up examinations may allow for early detection of the disease. If there is a family history of RB, the child should be examined by an eye doctor (ophthalmologist) soon after the child is born. These exams should continue every three to four months until the child is three to four years of age. The exams are then done every six months until the child reaches five to six years of age. Alternatively, if the child has genetic testing and it is found that they do not carry the inheritable form of RB, this intensive testing may not be needed, but this decision should be discussed with a phyician. If a child is noted to have no red reflex (as described below), they should be brought to medical attention.

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