What is retinoblastoma and what is the pattern of inheritance for this type of cancer?
There are two types of retinoblastoma: Show
Sixty percent of children have only one eye affected. Most of these children have the sporadic form of retinoblastoma. However, about 10%–15% may have hereditary retinoblastoma. Forty percent of patients have both eyes affected. These children always have the hereditary form. It is important to know whether a person has the hereditary or the sporadic form of retinoblastoma. The hereditary form carries specific health risks that are not found with the sporadic form. Children with hereditary retinoblastoma are at an increased risk to:
Children with sporadic retinoblastoma are not at risk to transmit the disease to their children. Their risk for developing second cancers is much less than the risk for children with hereditary retinoblastoma. What causes hereditary retinoblastoma?Hereditary retinoblastoma is caused by changes in a gene known as RB1. Genes carry important information that tells our body’s cells how to function. The RB1 gene controls how cells grow and divide. One of its main jobs is to prevent tumors from forming, particularly retinoblastoma. Normally, your cells carry two working copies of RB1. One is inherited from your mother and one from your father. Cells from people with hereditary retinoblastoma carry one working copy of RB1 and one copy that is altered. This alteration causes the gene to not work properly and is called a mutation. When the remaining working copy of RB1 becomes damaged within a cell of the developing retina, it is believed that this can lead to a retinoblastoma tumor. In about 10%–20% of hereditary retinoblastoma cases, this mutation is passed down from a parent who also has hereditary retinoblastoma. In the other cases, the affected child has a new mutation that was not present in either parent. While this child is the first one in the family to have hereditary retinoblastoma, he or she can now pass on the disease to 50% (1 in 2) of his or her future offspring. What is the cancer risk for children with hereditary retinoblastoma?Hereditary retinoblastoma might start in just one eye. But the chances of it developing in the second eye are high because cells in the other retina contain the altered RB1 gene.
How are children with hereditary retinoblastoma screened for cancer?Children with hereditary retinoblastoma should be watched closely for the development of possible eye tumors. The goal is to detect cancer at the earliest and most treatable stage in order to minimize the therapy that is required and to preserve vision. A specialized eye doctor called an ophthalmologist will conduct an eye exam as early as possible, even starting at birth, if there is a family history of retinoblastoma. Exams should then continue every one to two months during the first two years of life, and then less frequently as the child gets older. After age 5 years, regular yearly exams should occur for the rest of the patient’s life. The ophthalmologist will decide how often the exams should take place. Since there is also a small risk of tumors forming in the pineal gland, the child should have a magnetic resonance imaging (MRI) scan of the brain twice a year through age four years. Currently, no standard exists for screening children with hereditary retinoblastoma for other (also called secondary) cancers. Families should watch for any signs or symptoms (lumps, bumps, aches, pains, changes in moles or illness that does not go away) that cannot otherwise be easily explained. These should be evaluated by a health care provider, as they might be a sign of an underlying tumor. Patients should also see their regular health care provider at least yearly for a routine physical exam. How do children get hereditary retinoblastoma?In about 80%–90% of hereditary retinoblastoma cases, the child is the first person in the family to have the condition. In these cases, the RB1 mutation either arose in an egg or sperm cell that formed the child or in one of the child’s cells during pregnancy. Less often, a child will develop hereditary retinoblastoma because the mother or father also carries the RB1 mutation and passed it on to the child. No matter how they acquired the altered gene, people with hereditary retinoblastoma have a 50% (or 1 in 2 chance) of passing it on to their children. How is genetic testing for hereditary retinoblastoma done?All children with both eyes affected and about 10%–15% of children with a single eye affected will have hereditary retinoblastoma. Genetic testing may be performed to find out whether a person has the hereditary or sporadic (non-hereditary) form of retinoblastoma. Testing when eye tumor tissue can be used
Testing when eye tumor tissue is not available
RB1 genetic test results can provide important information for other family members. When a specificRB1 mutation is found, other family members can be tested to see if they carry the same mutation. Prenatal testingParents may undergo prenatal testing to find out whether a pregnancy is affected with a known RB1mutation in the family. Testing may take place either before pregnancy occurs or after an embryo is formed. Those considering prenatal testing should work with a genetic counselor to review the pros and cons of the tests. The genetic counselor will also help parents consider how they wish to handle the results of the testing. Testing that occurs before pregnancy — Testing that happens before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT offers a way to test embryos for a known RB1 mutation before placing them into the uterus. Testing that occurs during pregnancy — Testing can be used to determine if a pregnancy is affected with a known RB1 mutation. A doctor gathers cells from the pregnancy in one of two ways:
Once these tissues are collected, DNA is isolated and checked for the presence of the RB1 mutation identified in the family. Both of these tests carry minor risks and should be discussed with an experienced doctor and/or genetic counselor. Special concernsGenetic testing for hereditary retinoblastoma is a complex process. Those thinking about testing should take time to consider the benefits and risks. They should discuss the process with a genetic counselor before undergoing the testing. If they choose testing, they should review the test results with the health care provider or genetic counselor to be sure that they understand the meaning of the results. Sometimes, children or adults with hereditary retinoblastoma experience sadness, anxiety or anger. Parents who passed on an altered RB1 gene to one or more of their children can feel guilty. It is also possible that a person who is found to have an altered RB1 gene could have more trouble getting disability insurance or life insurance. Are there other special health care needs for children with hereditary retinoblastoma?Survivors of hereditary retinoblastoma have a higher risk of other cancers later in life. It is recommended that they adopt healthy habits such as:
As children with hereditary retinoblastoma grow up, they should continue to have regular physical checkups and screenings and maintain a primary pediatrician/physician. That way, any cancer can be found early at the most treatable stage. People with hereditary retinoblastoma should also watch closely for symptoms that could signal cancer, such as:
Parents of children with hereditary retinoblastoma should seek medical help if these symptoms appear. Last updated: 5/2020 What type of cancer is retinoblastoma?Retinoblastoma is a cancer that starts in the retina, the very back part of the eye. It is the most common type of eye cancer in children. Rarely, children can have other kinds of eye cancer, such as medulloepithelioma, which is described briefly below, or ocular (eye) melanoma.
What is retinoblastoma caused by?A genetic mutation (a change in the child's genes) causes retinoblastoma. The gene that causes retinoblastoma is called RB1. The mutation causes cells in the eye to grow uncontrollably, forming a tumor. Around 40% of the time, the child inherits the RB1 mutation from a parent (heritable retinoblastoma).
What type of gene is the retinoblastoma gene and how does mutation in this gene give rise to cancer?In children with the heritable genetic form of retinoblastoma there is a mutation on chromosome 13, called the Rb1 gene. The genetic codes found in chromosomes control the way in which cells grow and develop within the body[5]. If a portion of the code is missing or altered (mutation), a cancer may develop.
Is retinoblastoma always inherited?Approximately 60 percent of cases of retinoblastoma are non-heritable and 40 percent are heritable. All of the non-heritable cases affect only one eye (unilateral). Of the 40 percent of cases that are heritable, approximately 85 percent of patients will develop multiple tumors affecting both eyes (bilateral).
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