Retinoblastoma

Most people have two functioning copies of the RB1 gene. The RB1 gene is a tumor suppressor. This means that its job is to stop tumors from developing. Changes or mutations in the RB1 gene result in a gene that cannot function. If the gene cannot function, it cannot do its job to stop tumor growth. This is why tumors develop.

The RB1 gene is especially important in the eye, specifically in the part called the retina. Tumors that develop in this part of the eye are called retinoblastoma.

If there is retinoblastoma in your family, you may be wondering if other people need to be tested. Genetic counselors are specialized in interpreting and analyzing genetic tests and family histories to give you the most accurate risks for specific family members.

To find other people with retinoblastoma, you may want to look at online support groups.

The WeCHope Foundation has an up to date list of active online support groups. Please visit their site for more information.

The Children’s Hospital of Philadelphia also has a page devoted to health resources including books, online support, camps, and other resources. Find more information here.

Your doctor may know more about local support groups, or may connect you with other families with a similar diagnosis.

Genetic testing for retinoblastoma can be done in the tumor itself and/or in the blood or saliva. If there is a biopsy of the tumor done, doctors will look to see if there are RB1 mutations in the tumor itself. In all types of retinoblastoma, hereditary and non-hereditary, we expect to find two RB1 mutations. Once the RB1 mutations are known, the child can be tested to see if either of those mutations are present in the other tissues. Typically blood or saliva is used.

Early diagnosis of retinoblastoma can help make treatment easier. Treatment for retinoblastoma is based on the type and stage of the tumor. Treatments may include removing the eye and chemotherapy, among others. Your medical team will work with your current doctors to organize the treatment, tests, and specialists you need. Your doctor may also be able to refer you to a center of excellence near you.

The care team at each institution may be different, but will typically include pediatric oncologists who specialize in the treatment of retinoblastoma, as well as pediatric ophthalmologists, surgical oncologists, pediatric oncology nurses, radiation oncologists and other medical specialists. You may also wish to see a geneticist and/or genetic counselor.

Retinoblastoma may occur in one or both eyes. Sometimes a small part of the brain, called the pineal gland is also affected (pineoblastoma). When one eye is affected, it is referred to as unilateral retinoblastoma. When both eyes are affected, it is referred to as bilateral retinoblastoma. When both eyes and the brain are all affected, it is referred to as trilateral retinoblastoma.

The retina is a part of the eye that senses light and color. When light enters the eye, the retina produces and image and sens the information to the brain. The retina is important in basic vision function.

Doctors may use the terms somatic and germline when talking about retinoblastoma.

Retinoblastoma (RB) is a type of eye tumor that develops during childhood. This tumor develops in the retina, which is a part of the eye that helps us detect light and color. RB may occur in one or both eyes.

The first sign of RB may be when parents notice a white light reflex (leukocoria) of the pupil that occurs when light is shone into a child’s eye at a certain angle, especially when taking a photo using a flash. Children may also appear to be cross eyed (strabismus), have redness or swelling of the eye, or have poor or worsened vision.

RB can be non-hereditary or hereditary, but both forms occur when both copies of the RB1 gene are affected by a gene change (mutation). Sixty percent of children affected with RB have a non-hereditary or sporadic form. The sporadic form of RB most often develops when one cell in one eye develops two disease causing variants or mutations in the RB1 gene. It is not associated with an underlying RB1 gene change in every cell of the body or an increased risk for developing other tumors later in life.

The hereditary (or congenital) form of RB is related to an underlying genetic change (or mutation) in the RB1 gene which is found in every cell of the body and then the occurrence of a second disease causing gene change in the RB1 gene early in life. Hereditary retinoblastoma is often associated with tumors in both eyes (bilateral retinoblastoma) and also with increased risk of other cancers in adulthood.

Having a single underlying genetic change (or mutation) in the RB1 gene which is found in every cell of the body runs through families in an autosomal dominant pattern. This means that a person with hereditary retinoblastoma has a 50% chance of having a child with a RB1 mutation. Most people who inherit a RB1 mutation in all cells of their body will develop a second disease causing variant in RB1 that results in retinoblastoma, but not all.

Whether hereditary or not, if RB tumors are not treated, they can travel outside of the eye to affect other organs. Overall, with treatment, more than 90% of individuals with RB go into remission. The chances of long-term survival for a child with RB are better if the tumor is treated before it spreads to other parts of the body.

Pineoblastoma is a tumor of the pineal gland of the brain. This is sometimes referred to as ‘trilateral’ retinoblastoma, since it typically occurs when both eyes are also affected.

Multifocal retinoblastoma (RB) means that there are multiple tumors in an individual with RB. Multifocal retinoblastoma can occur in one eye, or in both eyes. Multifocal retinoblastoma indicates an significantly increased change that an individual has an underlying RB causing RB1 mutation in every cell of their body.

Gonadal mosaicism (also known as germline mosaicism) can occur in any genetic condition, however it is more common in retinoblastoma. Gonadal mosaic means that a parent may have the RB1 mutation, but only in their sperm or egg cells. If a person with gonadal mosaicism has a blood or saliva test, it will not find a mutation. This is because they only that the mutation in their sperm or eggs. There is no way to test each sperm or each egg for a mutation.
A person who has gonadal mosaicism has a risk to have a child with retinoblastoma.

Enucleation is the medical term for removal of the eye. This is sometimes used as a treatment for retinoblastoma.

Some children have no symptoms of retinoblastoma, and are only diagnosed after seeing a doctor for routine screening. Other children may have a white reflection to the pupil (leukocoria), a ‘lazy eye’ (strabismus), vision problems, or an eye that is red or irritated. Watch for any changes in your body such as unintended weight loss, loss of appetite, unexplained pain or lumps, headaches and changes of vision that do not go away, and new or changed moles. It is important to see your doctor if you have any concerns.

Children with retinoblastoma (RB) have one or more tumors of the eye. Signs and symptoms of RB may include:

Retinoblastoma (RB) can be non-hereditary or hereditary, but both forms occur when both copies of a eye cell’s RB1 gene are affected by a disease causing gene change (mutation). The RB1 gene is a tumor suppressor gene, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way. When there are no working copies of the RB1 gene, cell growth is not properly regulated and a RB occurs. More than 2,500 variants in the RB1 gene have been identified in individuals with retinoblastoma or in the RB tumors themselves.

All genes are "spelled" in a specific way that guides the growth, development, and function of the body. Sometimes, changes in that gene spelling are identified. Not all changes or "mispellings" are disease causing.

Changes can be classified as pathogenic (causing disease), benign (normal), or variant of uncertain significance. Variants of uncertain significance are changes that we do not know what they mean. They may cause the disease, or they may be completely normal. If you have a change in RB1 and would like to learn more about it, you should contact a genetic counselor.

The symptoms of retinoblastoma (RB) are usually seen in children before age 5. Some children will have no symptoms of RB before diagnosis; however the most common symptoms include: a white reflection in the pupil of the eye, especially when taking flash photo (leukocoria), a ‘lazy eye’ that turns inward or outward (strabismus), vision problems, or red and irritated eyes. Other symptoms may include:

The symptoms of retinoblastoma usually present before age five. Some children may have no symptoms of retinoblastoma before diagnosis, while other may have several medical issues related to their eye’s appearance and function. Parents may notice:

The eye tumors associated with retinoblastoma (RB) typically do not affect adults. However, survivors of childhood RB with the hereditary form of RB are at a higher risk to develop additional or secondary cancers in adulthood than those who had non-hereditary retinoblastoma.

These secondary cancers may include:

Soon after diagnosis of Retinoblastoma, the next step is to determine how far the RB has progressed. Accordingly, there are several evaluations that may be recommended by your doctor including:

Individuals who have a family member with retinoblastoma may be interested in learning their chance of having it too. The type of retinoblastoma (hereditary or nonhereditary) in the family is important to know, since each type has different risks. The family members can talk with a medical geneticist or genetic counselor about the risk and genetic testing options.

If a child is diagnosed with retinoblastoma, families may be interested to learn about the risk of other family members developing the disease. There are two forms of retinoblastoma: hereditary and non-hereditary.

Hereditary retinoblastoma is due to an RB1 mutation throughout the body, in every cell, including the cells of the eye. Hereditary retinoblastoma can be passed down from one generation to the next. Non-hereditary retinoblastoma is due to an RB1 mutation in the eye only. Non-hereditary retinoblastoma is not passed down from one generation to the next.

If someone in your family has been diagnosed with retinoblastoma, talk with a genetic counselor about the risks to specific family members.

There is no newborn screening done for retinoblastoma. Children will typically have a screening eye exam with their pediatrician to look for any abnormalities. If there is a family history of retinoblastoma the child will be screened from an early age by an ophthalmologist. If there is a known RB1 mutation in the family, the baby can be tested at birth.

Genetic testing for retinoblastoma can be done in the tumor itself and in the blood or saliva. If there is a biopsy of the tumor done, doctors will look to see if there are RB1 mutations in the tumor itself. In all types of retinoblastoma, hereditary and non-hereditary, we expect to find two RB1 mutations. Once the RB1 mutations are known, the child can be tested to see if either of those mutations are present in the blood or saliva.

Retinoblastoma clinical research is focusing mainly on treatment. The most recent clinical research in retinoblastoma can be found at the American Cancer Society and at ClinicalTrials.gov.

Treatment for retinoblastoma is based on the type and stage of the tumor. Treatments may include removing the eye and chemotherapy, among others.

You may wish to be seen at a center of excellence if there is one in your area. Centers of excellence are centers that specialize in the treatment of patients with conditions like retinoblastoma. At most centers, they will see pediatric oncologists who specialize in the treatment of retinoblastoma, as well as pediatric ophthalmologists, surgical oncologists, pediatric oncology nurses, radiation oncologists, genetic counselor, and other medical specialists who work as a team to answer questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan. The center of excellence will work with your current doctors to organize the treatment, tests, and specialists you need.

Retinoblastoma is panethnic in that it can be found in people of all races, ethnicities, and in all countries. It is not more common among one group or another.

Hereditary retinoblastoma is a disorder caused by a mutation in the RB1 gene in every cell of the body. Not every person with a mutation will develop a second mutation in the RB1 gene that results in RB or other symptoms. Less than 10% of people with a mutation will not develop retinoblastoma. This is called decreased penetrance.

Individuals who had retinoblastoma (RB)as a child, may be curious to know if their children will also have RB. This risk depends on the type of RB affecting them: hereditary and non-hereditary.

In hereditary retinoblastoma, there is an RB1 mutation in all of the body’s cells at birth. In this case, the individual has a 50% chance of passing the mutation on to their children. If the child inherits the mutation they have over a 90% chance of developing RB. If the child does not inherit the mutation, the risk is back to the average population risk to develop RB.

In non-hereditary RB, there is no identifiable mutation in your cells unaffected by RB. In this case, there is about a 5% chance of that individual’s children having RB. This chance is more than that of a person in the general population, but smaller than someone who has hereditary retinoblastoma.

To learn more about the type of retinoblastoma you had, talk with your doctor. You may also wish to reach out to a genetic counselor to be tested for an RB1 mutation or learn about the inheritance of RB in families.

In the United States, about 250-350 children are diagnosed with retinoblastoma each year. It is estimated to occur in 1 in 15,000 to 1 in 20,000 babies born worldwide.

There are two types of retinoblastoma: hereditary and non-hereditary.

Hereditary Retinoblastoma:

There are multiple ways that you can donate money for retinoblastoma research. The list below includes some ideas, but is limited. There may also be other organizations that would benefit from your generosity.

There are a few different tests that are usually done for retinoblastoma: an eye exam and genetic testing. First, an ophthalmologist will look into the eye to determine if there is anything unusual after the appearance or function of the eye. An MRI may be done to get a better view of the tumor, as well as to rule out other possible eye conditions. A biopsy of the tumor may be done if the eye is removed. There may also be a saliva or blood test to look for mutations or changes in the RB1 gene.

The most recent clinical research in retinoblastoma can be found at the American Cancer Society and at ClinicalTrials.gov.
Keep in contact with support groups. Emails and newsletters will typically contain the most up to date information about current research

There are many regional center of excellence in retinoblastoma (RB) across the United States.
You may wish to talk with your doctor to see if there are any near you. A sampling Major centers include:

Retinoblastoma is not gender specific. It affects boys and girls equally.

All retinoblastoma tumors have changes in the RB1 gene. However, sometimes one of these changes is found in all the cells of the body and others only upon testing of the tumor only.

Individuals with hereditary retinoblastoma are at increased risk of developing secondary cancers in their lifetime. It is recommended that individuals with hereditary retinoblastoma limit exposure to DNA damaging agents such as:

Doctors can cure retinoblastoma (RB) in up to 95% of cases if treatment is begun before the tumor has spread. If the tumor has spread outside the eye, the cure rate is much lower. The chance for remission, cure, or decreased survival depends from person to person and should be discussed with the individual with RB’s physician.

Children can have retinoblastoma (RB) without having inherited a change in the RB1 gene. RB happens due to a change in the RB1 genes in cells of the eye. The normal mechanism that stops cells from growing gets turned off. This allows those cells to grow too fast. This overgrowth of cells causes a tumor: retinoblastoma. The first change disease causing change in RB1 gene is inherited in on 30% of individuals affected by RB. That means a child can have RB without having inherited RB1 genes changes in every cell of their body or being at risk of passing an RB1 gene to their children.

If an individual in a family has had retinoblastoma, they may be interested in genetic testing for future pregnancies. If there is a known RB causing RB1 mutation in the family, preconceptional and prenatal testing is possible. If there is not a known mutation, prenatal testing is not possible. The options for prenatal testing while pregnant may include:

Retinoblastoma typically occurs before age 5. The average age at diagnosis is between age 1 and age 2.

Survivors of retinoblastoma are at increased risk of developing other tumors as they age. Limiting exposure to UV light, external beam radiation, tobacco, and other DNA damaging agents can help reduce these risks. According to some studies, risks for secondary cancers may also be reduced if exposure to chemotherapy before age 1 is limited.

Retinoblastoma may also be called retinal glioma or RB.

Some other conditions can resemble retinoblastoma, such as:

Support groups for retinoblastoma may range from those focused on RB specifically to those with broader resources for family and patient support before, during, and after therapy.

The WeCHope Foundation has an up to date list of active online support groups focused on RB. Please visit their site for more information.

The Children’s Hospital of Philadelphia also has a page devoted to health resources including books, online support, camps, and other resources. Find more information here.

Genetic does not always mean inherited. A person can have a genetic disease that was not inherited from a parent. Retinoblastoma has two ‘forms’: hereditary and non-hereditary. Even a person who has no family history of retinoblastoma can have the disorder.

There are two forms of retinoblastoma: hereditary and non-hereditary.