Retinoblastoma and genetics
Retinoblastoma is a rare cancer that primarily affects the retina, the light-sensitive tissue at the back of the eye, often resulting in tumors that can grow uncontrollably if not treated. It predominantly occurs in children under the age of five and has a higher incidence in certain regions, including Asia and Africa. The RB1 gene, located on chromosome 13, plays a crucial role in this condition, as it encodes a tumor-suppressor protein that helps regulate cell growth in retinal cells. Mutations in the RB1 gene can lead to either heritable (germinal) or non-heritable (nongerminal) forms of retinoblastoma, with germinal cases often running in families and typically following an autosomal dominant inheritance pattern. Symptoms may include abnormal eye appearance, such as a white pupil instead of red, and crossed eyes. Diagnosis typically involves thorough physical exams and imaging techniques to assess the extent of the cancer. Treatments vary based on cancer progression and may include surgery, radiation, chemotherapy, and other therapies. Early detection through genetic counseling and regular eye exams is vital for improving treatment outcomes and monitoring for associated risks of other cancers.
Retinoblastoma and genetics
DEFINITION Retinoblastoma is a rare type of cancer found in the eye. In retinoblastoma, one or more tumors form in the retina, a layer of light-sensitive tissue that lines the back of the eye. The retina converts visual images into nerve impulses in the brain that allow people to see. If not treated, the tumors will continue growing. The cancer may grow along the optic nerve and reach the brain, or it may travel to other parts of the body.
Cancer occurs when cells in the body—in this case, retina cells—divide without control or order. Normally, cells divide in a regulated manner. If cells keep dividing uncontrollably when new cells are not needed, a mass of tissue called a growth or tumor forms. Tumors can invade nearby tissue and spread to other parts of the body.
Risk Factors
Typically individuals who are less than five years are at risk for retinoblastoma, as are family members with the disease. According to the National Institute of Health in 2024, retinoblastoma accounted for about 3 percent of cancers occurring in children younger than fifteen years. It affects approximately one in 16,000–18,000 newborns worldwide and is most common in Asian and African countries.
Etiology and Genetics
The RB1 gene, found on the long arm of chromosome 13 at position 13q14.2, is responsible for almost all cases of retinoblastoma. This gene specifies a protein known as retinoblastoma-associated protein (pRb) that normally acts as a tumor-suppressor protein in several cell types, including retinal cells. Tumor-suppressor proteins act in a variety of ways to regulate cell growth by preventing cells from dividing too fast or at inappropriate times. Specifically, pRb represses the transcription of several other genes whose protein products are needed in order to initiate a new round of DNA replication in the cell. When functional pRb is unavailable as a result of mutations in the RB1 genes, this control of cell growth is lost, and tumors may develop.
Retinoblastomas are often categorized as being either germinal or nongerminal. In germinal retinoblastomas, which make up about 40 percent of all cases, the mutated RB1 genes are found in all cells in the body. These are the cases that can be inherited and in which there is often a family history of the disease. In nongerminal cases, which make up about 60 percent of all cases, the mutations in RB1 have been acquired over time in the retinal tissue only, and affected individuals are not at risk of passing them on to their offspring. In germinal retinoblastoma, the inheritance pattern is most often consistent with an autosomal dominant mode of transmission, meaning that a single inherited copy of the mutation is sufficient in most cases to cause expression of the disease. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Many cases of germinal retinoblastoma, however, result from a spontaneous new mutation, so in these instances affected individuals will have unaffected parents.
Symptoms
Symptoms of retinoblastoma are usually noticed by the parent or caregiver. These may include, but are not limited to, eyes that do not look normal, often described as having a glazed look or a “cat’s eye”; pupils that look white rather than red when a light is directed at the eyes, as seen in a photograph; or eyes that appear to be crossed or looking in different directions. Less common symptoms include eyes that grow in size, eye pain, redness in the white part of the eye, tearing, a pupil that may not respond to light, and the iris (colored part of the eye) changing color.
Screening and Diagnosis
The doctor will ask about a child’s symptoms and family medical history and will perform a physical exam. Many retinoblastomas are found during routine physical exams. If a tumor is suspected, the child will usually be referred to a specialist for a more complete eye exam. In children with a family history of the disease, eye exams often begin within a day or two of birth. Additional eye exams are scheduled at regular intervals thereafter.
Once retinoblastoma is found, staging tests are performed to find out if the cancer has spread and, if so, to what extent. Treatment depends on the stage of the cancer. The cancer may be localized to the eyes, or it may have spread to tissues around the eye or in other parts of the body.
Tests may include an eye exam, in which the pupil is dilated with eye drops and the inside of the eye is examined with a lighted instrument that allows the examiner to view structures inside the eye; ultrasound, in which sound waves are used to examine the inner part of the eye; and a magnetic resonance imaging (MRI) scan, in which magnetic waves are used to make pictures of the inside of the body. An MRI can be used to check the spread of the cancer to the brain or other tissue. A computed tomography (CT) scan is a type of X-ray that uses a computer to make pictures of the eye. CT scans of other areas of the body may be done to check if the cancer has spread. General anesthesia may be given to keep the child still during close examination and testing.
Treatment and Therapy
The child will likely be referred to a specialist for treatment. Without treatment, the cancer cells will continue to grow. Treatment aims to cure the cancer and preserve sight. Options vary, depending on whether the disease is limited to the eye or has spread, how large the tumor is, and where in the eye it is located. Therapies may be used alone or in combination.
A common treatment option is surgery. This involves surgical removal of the entire eye and as much of the optic nerve as possible. The optic nerve is the nerve leading from the eye to the brain and is responsible for vision. Surgery may be used for a large tumor in one eye.
Radiation therapy is a form of treatment that involves the use of radiation to kill cancer cells and shrink tumors. Radiation may be external radiation therapy, in which radiation is directed at the tumor from a source outside the body, or internal radiation therapy, in which radioactive materials are placed into the body near the cancer cells.
Cryotherapy, used on small tumors, is the use of cold to freeze and destroy cancer cells. Thermotherapy uses heat to kill cancer cells. In photocoagulation, lasers are used to destroy a small tumor.
Chemotherapy is the use of drugs to kill cancer cells. This treatment may be given as a pill, as an injection, or through a catheter. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells but also some healthy cells.
Prevention and Outcomes
Genetic counseling and close monitoring and screening for people at risk for retinoblastoma can help detect the disease early if it occurs. Early diagnosis and treatment improve the chance of successful treatment. Children born into families with a history of retinoblastoma should have regular eye exams to screen for development of the tumor. All children should have regular eye screenings by their doctor.
Genetic counseling may help determine a person’s risk of developing retinoblastoma. If a patient has retinoblastoma or has a family history of the disorder, he or she can talk to a genetic counselor when deciding whether to have children.
Patients who have been treated for retinoblastoma require regular medical exams to assess the success of treatment and to check for recurrence or bilateral disease. Children with retinoblastoma are at increased risk for an associated brain tumor and other cancers in the body and should be monitored in order to check for other cancers.
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