Rhabdoid Tumor Predisposition Syndrome

What causes rhabdoid tumor predisposition syndrome?

The majority of rhabdoid tumor predisposition syndrome cases are caused by changes in a gene called SMARCB1 (also called INI1). Genes carry information telling cells within the body how to function. The SMARCB1 gene helps to control how cells grow, divide and die.

Most people without rhabdoid tumor predisposition syndrome carry two working copies of the SMARCB1 gene in their cells. One copy of SMARCB1 is inherited from the mother and one from the father. Cells from people with rhabdoid tumor predisposition syndrome carry one working copy of SMARCB1 and one copy that is changed. This change causes the gene to not work properly. It is called a SMARCB1 mutation.

A few children with rhabdoid tumor predisposition syndrome inherit their SMARCB1 mutation from a parent who also has the syndrome. However, most children have a new SMARCB1 mutation that did not come from a parent. These children have no history of the syndrome in their family. In these cases, the gene change either happened in an egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have rhabdoid tumor predisposition syndrome. No matter how they acquired the gene mutation, people with rhabdoid tumor predisposition syndrome have a 50% (or 1 in 2) chance of passing it on to their children.

Most people born with one SMARCB1 mutation are healthy at birth. As they get older, the second copy of the SMARCB1 gene might also become changed in one or more cells of the body. When this happens, those cells can develop into a tumor. This is why people with rhabdoid tumor predisposition syndrome have a greater risk of developing rhabdoid tumors and schwannomas.

Very rarely, rhabdoid tumor predisposition syndrome is caused by changes in a different gene called SMARCA4. Testing for this gene is guided by information from the tumor and/or family history.

How are children with rhabdoid tumor predisposition syndrome screened for tumors?

People with rhabdoid tumor predisposition syndrome should be managed by a doctor who knows this condition well. We recommend screening for anyone with rhabdoid tumor predisposition syndrome, even though not everyone with the syndrome will develop tumors. The goal of screening is finding and treating tumors early to allow the best outcome for patients.

Doctors have not yet agreed on standard screening tests for people with rhabdoid tumor predisposition syndrome. Some doctors recommend that people with this condition have a brain MRI exam and a abdominal ultrasound as soon as they are diagnosed, and then regularly after that. An MRI uses magnetic fields and radio waves to make images of the inside of the body. An ultrasound uses sound waves to make images of the inside of the body.

These recommendations are the most current. It is possible that what is recommended may change over time as doctors learn more about rhabdoid tumor predisposition syndrome. Because this condition is rare and complex, it is important that parents seek out and discuss all screening options for their child with a doctor who works regularly with this syndrome.

How is genetic testing for rhabdoid tumor predisposition syndrome done?

The doctor may suspect rhabdoid tumor predisposition syndrome after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members.

The genetic counselor or doctor will record which family members have developed tumors, what types of tumors and at what ages these tumors occurred. From this information they will create a family tree. Doctors and genetic counselors will look at the family tree to find out:

• If there are more cancers than normal,
• If cancers occurred at younger-than-expected ages and
• If the types of tumors match up with what might be seen in those with rhabdoid tumor predisposition syndrome.
  

If rhabdoid tumor predisposition syndrome is suspected in a child or other family members, the doctor or genetic counselor will likely recommend genetic testing of the SMARCB1 gene. In some cases, they may recommend testing the SMARCA4 gene as well.

How is genetic testing for rhabdoid tumor predisposition syndrome done?

Testing when rhabdoid tumor tissue can be used

• Rhabdoid tumor genetic testing is best performed by starting with a sample of the rhabdoid tumor.
• DNA (genetic material) is isolated from a piece of the tumor.
• The tumor DNA is screened for any changes in the two copies of the SMARCB1 gene using methods such as DNA sequencing. In DNA sequencing, a genetic specialist checks the lettering (spelling) of the two copies of a gene to that of a normal sample. If there are differences, the specialist then decides if those differences might have caused the tumor. Please note that other methods may also be used, especially when the results of DNA sequencing are negative or unclear. These other tests look for changes that could affect the SMARCB1 gene but that may not be found by DNA sequencing.
• If the two SMARCB1 mutations are found that could have led to the rhabdoid tumor forming, a separate blood sample from the person is checked to see if it shows one of these mutations.
• Finding a SMARCB1 mutation in the blood supports a rhabdoid tumor predisposition syndrome diagnosis.
• Not finding a SMARCB1 mutation in the blood usually means that the child has a sporadic rhabdoid tumor.

Testing when rhabdoid tumor tissue is not available

• SMARCB1 genetic testing can be performed on a blood sample from a child with a rhabdoid tumor, even when there is no tumor for testing. In these cases, it is sometimes harder to understand the test results.
• If a disease-associated SMARCB1 mutation is found, the patient has rhabdoid tumor predisposition syndrome.
• If no SMARCB1 mutation is found, this does not rule out rhabdoid tumor predisposition syndrome. It is possible that a mutation is present but it was not found because of limits in the testing process. For this reason, it is best to test the blood after the rhabdoid-causing SMARCB1 mutations have first been found in a tumor.
• If rhabdoid tumor tissue can be sampled at a future time, the tumor testing can be performed.

SMARCB1 genetic test results can provide important information for other family members. If aSMARCB1 mutation is found, the genetic counselor will work with the family in the following ways:

• To help the family understand the cancer risks of rhabdoid tumor predisposition syndrome
• To find out if other family members should consider testing
• To help with decisions about prenatal genetic testing

Prenatal Genetic Testing

Parents may undergo prenatal testing to find out if the pregnancy is affected with a known SMARCB1 mutation in the family. Testing may take place either before pregnancy occurs or during pregnancy (after the 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 can 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 SMARCB1 mutation before placing them into the uterus.

Testing that occurs during pregnancy — Testing can be used to see if a pregnancy is affected with a known SMARCB1 mutation. A doctor gathers cells from the pregnancy in one of two ways:

• Chorionic villus sampling (CVS) — during the first trimester (first three months)
• Amniocentesis — during the second trimester or later (last 6 months)

Collected tissue can be checked for the presence of the SMARCB1 mutation identified in the family.

Both of these tests carry minor risks and should be discussed with an experienced doctor or genetic counselor.

Special concerns

Genetic testing for rhabdoid tumor predisposition syndrome 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 testing is done. If they choose testing, they should review the test results with the doctor or genetic counselor to be sure they understand the meaning of the results.

Sometimes families with rhabdoid tumor predisposition syndrome can feel sad, anxious or angry. Parents who pass on a SMARCB1 mutation to one or more of their children can feel guilty. Some people with a SMARCB1 mutation could have trouble getting disability coverage, life insurance, or long-term care insurance in some states. More information about genetic discrimination can be found at  www.ginahelp.org.

Are there other special health care needs for children with rhabdoid tumor predisposition syndrome?

People of any age with rhabdoid tumor predisposition syndrome have a higher risk of cancer. They should monitor their health and adopt healthy habits throughout life. It is important to continue to have regular physical checkups and screenings. That way, any tumor can be found early at the most treatable stage.

Other ideas for reducing the risk of cancer include the following:

• Eat a healthy diet with lots of fruits and vegetables
• Get regular exercise
• Avoid smoking or using tobacco products
• Avoid secondhand smoke
• Avoid excess sun exposure and always wear sunscreen, hat and protective clothing when out in the sun

People with rhabdoid tumor predisposition syndrome should watch closely for general signs or symptoms that could signal cancer:

• Unexplained weight loss
• Loss of appetite
• Aches, pains, lumps or swelling that cannot be explained
• Headaches or changes in vision or nerve function that do not go away

It is important to seek medical help if anything unusual appears.

Last updated: 05/2020