Li-Fraumeni Syndrome

Cancer risk with Li-Fraumeni syndrome

LFS can cause a variety of cancers. It is hard to tell what kind of cancers may happen, where in the body, or when they will occur. We do know that:

• By age 30, 50% (1 in 2) of all people with LFS will develop some kind of cancer.
• By age 60, their risk of developing cancer increases to about 80–90%
• People with LFS are more likely to develop multiple cancers and cancers caused by previous radiation.

People with LFS may get cancer in their:

• Brain
• Breasts
• Bones
• Blood
• Adrenal gland (a tiny gland located on top of each kidney)
• Muscles
• Connective tissues that support and give shape to the body, like fat or cartilage

Less commonly, people with LFS can develop cancers in other parts of the body such as the:

• Skin
• Thyroid gland
• Lungs
• Esophagus, stomach, pancreas, or colon (digestive system)
• Kidney or bladder (urinary system)
• Uterus, ovaries, prostate, or testicles (reproductive system)

Causes of Li-Fraumeni syndrome 

LFS is caused by changes in a gene known as TP53. This gene carries important information that controls cell growth and function. A change that causes the gene to not work correctly is called a mutation.

How Li-Fraumeni syndrome is inherited

Everyone has 2 copies of the TP53 gene. Children without this disorder carry 2 normal copies of the TP53 gene in their cells. One copy of TP53 is inherited from the child’s mother, and the other comes from the child’s father.

Children who do have LFS have 1 TP53 gene with a mutation. This mutation makes it harder for the cells to control their growth and function. The other copy of the TP53 gene may be lost or changed in cells. When this happens, cancers may develop.

Most children with LFS inherit the syndrome from 1 parent who also has LFS. However, some may develop a new TP53 mutation that did not appear to come from either parent. These children are the first in their families to have LFS.

No matter how people with LFS get their TP53 mutation, they have up to a 50% (1 in 2) chance of passing it on to their children.

Diagnosis of Li-Fraumeni syndrome

Health history

A health care provider may suspect that your child has LFS after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

• There are more cancers than normal in your family
• These cancers happened at a younger age than expected
• The cancers are those that are seen in Li-Fraumeni syndrome

Your provider or genetics counselor may recommend TP53 genetic testing if they suspect LFS.

Learn more about types of genetic tests.

Genetic testing for Li-Fraumeni syndrome

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that looks for changes in the TP53 gene.

If your child has a TP53 mutation, the genetic counselor will work with your family to:

• Find out if other family members should consider testing for a TP53 mutation
• Help your family understand the increased cancer risk from LFS
• Give you information to help with your decisions about prenatal genetic testing

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known TP53 mutation. Testing may take place either before pregnancy occurs or during pregnancy.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known TP53 mutation before a provider places the embryo into the uterus.

Testing during pregnancy can help providers see if a pregnancy has a known TP53 mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
• Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for the TP53 mutation. Both tests carry minor risks. Discuss risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with LFS feel sad, anxious or angry after getting their test results. Parents may feel guilty if they pass the TP53 gene mutation to 1 or more of their children. People with a TP53 gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Monitoring and follow-up care for Li-Fraumeni syndrome

Monitoring and follow-up care for LFS depends on the location of tumors that may arise and a person’s overall health. Care may involve managing symptoms and surgical removal of any cancerous tissues or tumors. It may also include other treatments like chemotherapy to fight cancers.

Radiation therapy may be necessary for certain cancers but should be avoided when possible for LFS patients.

Because Li-Fraumeni is a complex syndrome, you should discuss screening options for your child with an experienced health care provider who knows this condition well. It is important to find an experienced health care provider for your child.

Cancer screenings for those with Li-Fraumeni syndrome

Studies suggest that close monitoring LFS patients for cancer is helpful. It is recommended that children and adults with LFS be watched closely for any cancer signs or symptoms. They should seek medical treatment if they notice symptoms. When cancer is detected early, it is easier to treat it.

Talk to a health care provider who is familiar with LFS about what cancer screening tests are needed. These tests may include:

• Physical exams that include a close check of skin health and neurological (nerve and brain) function
• Blood tests that include a complete blood count (CBC)
• Tests that screen for hormone-producing cancers in the adrenal glands
• Yearly magnetic resonance imaging (MRI) of the brain and body
• Ultrasounds of the abdomen

Adults with LFS may do some of the same tests. They may also need:

• Colonoscopy
• Women: breast exam performed by a health care provider
• Women: mammogram and a breast MRI exam

Living with Li-Fraumeni syndrome

People with LFS have a higher cancer risk. They should monitor their health and adopt healthy habits throughout their lifetime.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthy diet with lots of fruit and vegetables.
• Get regular exercise.
• Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (SPF 30 or higher) when out in the sun.
• Avoid unnecessary radiation exposure.
• Avoid smoking or the use of tobacco products.
• Avoid being around secondhand smoke.
• Avoid excessive alcohol use.

Li-Fraumeni syndrome care at St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
• Physical exams to check for genetic disease
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1^st degree) relatives

LFS increases your child’s risk for many types of cancer.

If you have questions about the Genetic Predisposition Clinic and care for Li-Fraumeni Syndrome, email our team at GPTeam@stjude.org.

Resources outside St. Jude