Li-Fraumeni Syndrome

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome (lee-FRAH-meh-nee) is a rare hereditary or genetic disorder that increases the risk you and your family members will develop cancer. People who are female at birth who have Li-Fraumeni syndrome have a nearly 100% chance of developing breast cancer. All people who have Li-Fraumeni syndrome have a 90% chance of developing one or more types of cancer in their lifetimes and a 50% chance of developing cancer before age 30.

Li-Fraumeni syndrome can’t be prevented. But early and consistent cancer screenings and treatment can limit the syndrome’s impact on your life and your family’s lives. Meanwhile, researchers are using Li-Fraumeni genetic test results to identify new ways to treat cancers linked to Li-Fraumeni syndrome.

How common is this condition?

Li-Fraumeni syndrome is rare. Researchers estimate the syndrome affects 5 in 20,000 families worldwide.

What causes Li-Fraumeni syndrome?

Li-Fraumeni syndrome happens when something changes in the TP53 gene, which contains the instruction manual to make a protein called tumor protein 53, or P53. Your P53 protein is a tumor suppressor. It keeps your cells from dividing and growing too quickly or in an uncontrolled way, becoming tumors. When your TP53 gene changes, the P53 protein instruction manual changes as well, losing the how-to section for making P53. Without properly functioning P53 proteins, cells can divide uncontrolled and become cancers.

Most people with Li-Fraumeni syndrome inherited altered TP53 genes from one or both parents. But approximately 25% of people with the syndrome were born with an altered TP53 gene.

What are the symptoms of Li-Fraumeni syndrome?

Developing certain cancers at an early age is the most common symptom of Li-Fraumeni syndrome. The syndrome is linked to more than a dozen different kinds of cancer. Nine of these are considered core cancers because they are commonly seen in people with Li-Fraumeni syndrome. Those core cancers are:

• Soft tissue sarcoma. This is a rare type of cancer that can affect children and adults. Soft tissue sarcomas can develop in people’s muscles, tendons, fat, lymph and blood vessels. Treatments include surgery, chemotherapy, targeted therapies and immunotherapy.
• Osteosarcoma. This is a kind of bone cancer that typically affects teenagers. Treatments include surgery, chemotherapy, targeted therapies or cryoablation. Cryoablation uses liquid nitrogen to freeze cancer cells.
• Breast cancer. People who are female at birth and have Li-Fraumeni syndrome have a very high risk of developing breast cancer. Treatments include surgery, radiation therapy, immunotherapy and chemotherapy.
• Gliomas, including glioblastoma. This is a form of brain cancer that typically affects adults. It’s commonly treated with chemotherapy or targeted therapy. Targeted therapy focuses on proteins and genes that help cancer grow.
• Choroid plexus carcinoma. This is a rare brain cancer that usually affects young children. Treatments include surgery and chemotherapy.
• Medulloblastoma (Sonic hedgehog subtype.) These are rare fast-growing brain tumors that usually affect young children. Treatments include surgery and chemotherapy.
• Neuroblastoma. This is a rare type of cancer that forms in nerve tissue. It usually affects children under age 5. Treatments include surgery, chemotherapy and immunotherapy.
• Adrenocortical carcinoma. This is a type of cancer that forms on people’s adrenal cortex, which is the outer layer of their adrenal glands. Treatments include chemotherapy and surgery.
• Acute myeloid leukemia. This is a blood cancer that starts in people’s bone marrow. Treatments include chemotherapy, targeted therapies and monoclonal antibody therapies. Monoclonal antibody therapy is a type of immunotherapy.

What other cancers are associated with Li-Fraumeni syndrome?

The syndrome is linked to several other cancers, but the risk of developing these kinds of cancer is lower than the core cancers. Those cancers include:

• Lung adenocarcinoma. This is cancer that starts in cells near your lung’s periphery. It is the most common lung cancer. It’s treated with surgery, radiation therapy, targeted therapy and chemotherapy.
• Skin cancer, including melanoma. Skin cancer is treated with surgery, chemotherapy, radiation therapy and immunotherapy.
• Colon cancer. Treatments include surgery, chemotherapy and radiation therapy.
• Pancreatic cancer. Treatments include surgery, radiation therapy, chemotherapy, immunotherapy and targeted therapy. Targeted therapy focuses on certain genes and proteins that help cancer grow.
• Kidney cancer. There are several types of kidney cancers. Healthcare providers use surgery to treat kidney cancer.
• Thyroid cancer. Treatments include surgery, chemotherapy and hormone therapy.
• Ovarian cancer. Treatments include surgery and chemotherapy.
• Testicular cancer. Treatments include surgery, radiation therapy and chemotherapy.
• Prostate cancer. Treatments include surgery, radiation therapy and chemotherapy.

How is Li-Fraumeni syndrome diagnosed?

Healthcare providers use genetic testing to diagnose Li-Fraumeni syndrome. Before those tests, however, providers consider your medical history and your family medical history. Here are the criteria providers use to diagnose Li-Fraumeni syndrome:

• You have a sarcoma before age 45.
• Your parents, siblings or children are diagnosed with any cancer before age 45.
• Your grandparents, aunts, uncles, nieces, nephews or grandchildren are diagnosed with any cancer before age 45.

My family is at risk for cancer due to Li-Fraumeni syndrome. Can we be screened for early signs of cancer?

Yes, there is a recommended screening plan designed to identify early-stage cancers. There is one schedule for children from birth to age 18 and another for adults. Here’s an example:

Every three to four months

• Complete physical examination.
• Complete blood count (CBC) to check for leukemia and lymphoma.

The following tests check for signs of adrenocortical carcinomas:

• Abdominal ultrasound.
• Pelvic ultrasound.
• Urinalysis.

Every year

• Brain magnetic resonance imaging (MRI) to check for brain tumor symptoms.
• Whole-body MRI to check for signs of soft tissue and bone sarcoma.

What is the screening plan for adults?

The screening plan for adults pays particular attention to breast and gastrointestinal cancer screening. People with Li-Fraumeni syndrome are sensitive to radiation. That’s why breast cancer screenings don’t call for mammograms.

If you have Li-Fraumeni syndrome, you should talk to your healthcare provider any time you have headaches, bone pain or abdominal pain that doesn’t go away. Here’s an example:

Monthly

• Breast self-examination.

Every six months

• General physical examination.
• Breast examination by healthcare provider, starting at ages 20-25.

Every year

• MRI breast screening starting at ages 20 to 25.
• Brain MRI.
• Whole body MRI.
• Abdominal ultrasound.
• Pelvic ultrasound.
• Full-body skin check for melanoma.

Every two to three years

• Upper endoscopy.
• Colonoscopy.

How is Li-Fraumeni syndrome treated?

Li-Fraumeni syndrome increases your risk and your family’s risk for developing cancer. Healthcare providers treat the syndrome by identifying and treating cancers linked to Li-Fraumeni syndrome. If your regular screenings show signs of cancer, ask your healthcare provider about treatment options. People with Li-Fraumeni syndrome often are very sensitive to radiation, which means your cancer treatment shouldn’t include any form of radiation therapy.

How can I reduce the risk of developing one or more cancers linked to Li-Fraumeni syndrome?

You can reduce your risk by adhering to your cancer screening schedule and by avoiding activities that might increase your risks. For example, if you smoke, try to stop. If you work or spend a lot of time outside, remember to wear protective clothing and to use sunscreen.

What can I expect if I have Li-Fraumeni syndrome?

Being diagnosed with Li-Fraumeni syndrome means taking care of your and your family’s health with regular cancer screening.

How do I take care of myself?

You can take care of yourself and your family by following any recommended cancer screening plans and avoiding activities that increase your risk for developing cancer.

When should I see my healthcare provider?

People with Li-Fraumeni syndrome have an increased risk of developing cancer, including having more than one type of cancer at the same time. Even if you have a formal cancer screening program, contact your provider any time you notice a change in your body that might be a cancer symptom.

I’ve been diagnosed with Li-Fraumeni syndrome. What questions should I ask my healthcare provider?

If you have Li-Fraumeni syndrome, you probably have questions about how the syndrome will affect your health and the impact it might have on your children or your plans to have children. Here are some questions to help you with those conversations:

• How do I know if I have Li-Fraumeni syndrome?
• Will I develop cancer?
• What kind of cancer might I develop?
• I have children. Should I worry they might have Li-Fraumeni syndrome?
• Should I have genetic testing?
• How do I find out if I have cancer?

A note from Cleveland Clinic

Li-Fraumeni is a hereditary syndrome that increases the chance you, your siblings and your children will develop cancer. Understanding why you and your loved ones are at risk is the first step toward limiting Li-Fraumeni syndrome’s impact on your lives. Genetic testing can identify which family members have the syndrome so they can begin regular cancer screenings. Unfortunately, people with Li-Fraumeni syndrome can develop more than one cancer. That means a lifetime of vigilance. Ask your healthcare provider for help setting up regular cancer screenings and support.