Li-Fraumeni Syndrome

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome is a rare genetic disorder that increases the risk you and your family members will develop cancer. People assigned female at birth (AFAB) who have Li-Fraumeni syndrome almost always develop breast cancer. All people with this condition have a 90% chance of developing one or more types of cancer by age 60. About half develop cancer before they turn 40.

Li-Fraumeni syndrome can’t be prevented. But early and consistent cancer screenings and treatment can limit its impact on your life. Meanwhile, researchers are actively investigating new ways to identify and treat cancers linked to Li-Fraumeni syndrome.

How common is this condition?

Li-Fraumeni syndrome is rare. Researchers estimate that over 1,000 families worldwide carry the gene mutation that causes it. Less than 50,000 people in the United States have Li-Fraumeni syndrome.

What are the symptoms of Li-Fraumeni syndrome?

Developing certain cancers at an early age is the most common sign of Li-Fraumeni syndrome. So, the symptoms you experience will depend on the type of cancer you develop.

What cancers are associated with Li-Fraumeni syndrome?

The syndrome is linked to more than a dozen different kinds of cancer. Some are considered core cancers because they’re commonly seen in people with Li-Fraumeni syndrome. Those five core cancers include:

• Sarcomas. People with Li-Fraumeni syndrome are at risk of developing osteosarcoma and soft tissue sarcoma.
• Breast cancer. People AFAB who have Li-Fraumeni syndrome have a near 100% chance of developing breast cancer in their lifetimes.
• Brain cancer. Several types of malignant brain tumors are associated with this condition. Types include gliomas, choroid plexus carcinoma and medulloblastoma.
• Adrenocortical carcinoma. This type of cancer, which forms on the outer layer of your adrenal glands, is more common in people with this condition.
• Leukemia. Acute leukemia is associated with Li-Fraumeni syndrome.

Other cancers are associated with Li-Fraumeni syndrome but occur less often than the core cancers. They include:

• Colon cancer
• Kidney cancer
• Lymphoma
• Lung cancer
• Ovarian cancer
• Pancreatic cancer
• Prostate cancer
• Skin cancer
• Stomach cancer
• Testicular cancer
• Thyroid cancer

What causes Li-Fraumeni syndrome?

Li-Fraumeni syndrome happens when there’s a mutation (change) in the TP53 gene. This gene contains the instructions for making a protein called tumor protein 53, or P53. The P53 protein is a tumor suppressor. It keeps your cells from growing abnormally and becoming tumors.

When your TP53 gene changes, your body doesn’t make properly functioning P53 protein. Without properly functioning P53 proteins, cells can divide uncontrolled and become cancers.

People with Li-Fraumeni syndrome inherit altered TP53 genes from a biological parent in an autosomal dominant pattern. This means you only need to inherit a copy of the altered gene from one parent to increase your cancer risk.

Although most cases of Li-Fraumeni syndrome are inherited, it’s possible to have an original genetic mutation (de novo) without family history.

How is Li-Fraumeni syndrome diagnosed?

Healthcare providers use genetic testing to diagnose Li-Fraumeni syndrome. Before these tests, they consider your medical history and your family’s medical history. Here are the criteria providers consider if they suspect 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.

Once you receive a diagnosis, your provider will recommend a cancer screening schedule. Regular check-ins with your provider allow them to diagnose and treat any potential cancers early on.

How is Li-Fraumeni syndrome treated?

There’s no treatment specifically for Li-Fraumeni syndrome. For the most part, healthcare providers treat the cancers in a person with Li-Fraumeni syndrome the same way they would in someone without this condition. Cancer treatments may involve surgery or standard therapies like radiation and chemotherapy, among others.

There’s one important exception. People with Li-Fraumeni syndrome are more likely to develop cancers in response to radiation exposure. This means that if you have this condition, your provider will adjust your cancer treatment to minimize radiation therapy.

Can Li-Fraumeni syndrome be prevented?

Li-Fraumeni syndrome isn’t preventable. But you can reduce your chance of developing cancer by avoiding certain activities, like:

• Smoking.
• Drinking too much alcohol.
• Spending a lot of time outside without sun protection (like sunscreen).

Some people AFAB choose to have surgery to remove both breasts (prophylactic mastectomy) to reduce their breast cancer risk.

Still, even with these precautions, it’s possible to develop cancer if you have Li-Fraumeni syndrome. This is why one of the best things you can do is get regular screenings to catch cancers early, when treatment is most effective.

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. Research shows that cancer screenings in people with Li-Fraumeni syndrome improve survival rates. Screening schedules for children and adults are different.

An example screening schedule for children up to age 18 is as follows:

• Every three to four months: A complete physical examination and an abdominal ultrasound to check for adrenocortical carcinomas.
• Every year: Brain MRI (magnetic resonance imaging) to check for brain tumor symptoms and whole-body MRI to check for signs of soft tissue and bone sarcoma.

An example screening schedule for adults is as follows:

• Every six months: Breast exam by a healthcare provider (starting at ages 20 to 25).
• Every year: Physical exam, MRI breast screening (starting at ages 20 to 25), brain and whole-body MRI, ultrasounds of the abdomen and pelvis, full-body skin check for skin cancer.
• Every two to three years: Colonoscopy to check for colon cancer and upper endoscopy to check for other gastrointestinal (GI) cancers.

Currently, clinical trials are underway to identify medications that can potentially target the TP53 gene mutation in Li-Fraumeni syndrome and slow cancer progression. But more research is needed to understand the safety and effectiveness of these medications.

How do I take care of myself?

You can take care of yourself and your family by following recommended cancer screening plans. It’s a good idea to speak to a genetic counselor about future pregnancies. It’s important to understand the risks of passing along the altered TP53 gene to a child.

It’s also important to care for your emotional well-being. Living with a lifelong condition like Li-Fraumeni syndrome can take a physical and emotional toll. Reach out to a licensed therapist with a background in treating people with cancer or chronic conditions. Ask your healthcare provider to connect you with support groups for people living with rare, long-term diseases.

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.

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. You may also wonder about 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 likely is it that I will develop cancer?
• What signs and symptoms should I look out for?
• Should I worry that my family members might have Li-Fraumeni syndrome?
• Should I have genetic testing?
• Should I encourage my family members to get tested?