Li-Fraumeni syndrome

诊断

Li-Fraumeni syndrome usually is diagnosed when a genetic test finds a harmful TP53 gene change. Before recommending genetic testing, the healthcare team also looks at your personal and family histories of cancer.

Who needs genetic testing

A healthcare team may recommend TP53 genetic testing if:

• Someone in your family is known to have a harmful TP53 gene change. This may include a first-degree relative, meaning a parent, brother, sister or child. It also might include another close blood relative, such as an aunt, uncle, niece, nephew, grandparent or grandchild.
• Your personal or family history suggests Li-Fraumeni syndrome.

Two sets of criteria commonly used to decide if you need genetic testing are the classic Li-Fraumeni syndrome criteria and the Chompret criteria.

If all of these classic criteria apply, a care team may suggest genetic testing.

• You have a sarcoma before age 45.
• A first-degree relative has any cancer before age 45.
• Another first-degree or close blood relative on the same side of the family has any cancer before age 45 or a sarcoma at any age.

The classic criteria look for a pattern of cancer at young ages within a family.

The Chompret criteria aim to include people who may need testing even if their family does not meet the classic criteria.

If any of these Chompret criteria apply, a care team may suggest genetic testing:

• You have a cancer commonly linked to Li-Fraumeni syndrome before age 46 and you also have a first-degree relative or close blood relative who's had one of these cancers before age 56 or who's had more than one cancer. This doesn't apply if you have breast cancer and your family history is limited to breast cancer.
• You've had more than one cancer, with at least two of them linked to Li-Fraumeni syndrome and the first cancer was diagnosed before age 46. This doesn't apply if your cancers were breast cancer.
• You've had adrenal cancer, choroid plexus carcinoma or a certain type of rhabdomyosarcoma at any age, regardless of family history.
• You have breast cancer before age 31.

Genetic testing may be considered in some other situations. These include when:

• You've had a specific type of childhood leukemia.
• You've had a tumor that was tested and results showed a harmful TP53 gene change.

What to expect from genetic testing

Genetic testing often looks for a harmful TP53 gene change using a blood sample.

Sometimes a TP53 gene change is found in only a small number of blood cells. When this happens, it could mean:

• The gene change affects only some cells in the blood — and in the body. This is called mosaicism. A mosaic form of Li-Fraumeni syndrome may still increase cancer risk.
• The gene change affects a group of blood cells and is not found anywhere else in the body. This is not Li-Fraumeni syndrome and does not increase the risk of cancer.

If a blood test shows that only some cells have the gene change, you may need testing of other body tissue, such as the skin. This can show if the gene change is present in other places in the body, which may suggest it's mosaic Li-Fraumeni syndrome.

A genetic counselor or other healthcare professional trained in genetics can help explain what the result means for the person being tested and for family members.

Cancer screening

If you're diagnosed with Li-Fraumeni syndrome, regular cancer screening and medical exams are an important part of managing the risk of cancer. Some screening is recommended as early as infancy, and screening is done throughout life.

Screening may include:

• Physical exams. Children may have an exam every 3 to 4 months. Blood tests may be done in children to check for signs of leukemia or adrenal cancers. Adults may have a physical exam every 6 to 12 months. These exams look for signs of cancer.
• Whole-body MRI. An MRI scan of the body once a year can begin in infants. MRI does not use radiation.
• Brain MRI. This usually is done once a year and can start when a child is an infant.
• Ultrasound of the adrenal glands in children. Young children may have an ultrasound every 3 to 4 months to look at the adrenal glands.
• Skin checks. Both children and adults may need regular skin checks by a dermatologist.

Screening in adults also may include:

• Breast MRI and mammograms. For women with Li-Fraumeni syndrome, annual breast MRI usually starts at age 20. Annual mammograms also may be added starting at age 30. Breast cancer screening may be recommended earlier, depending on family history.
• Upper endoscopy and colonoscopy. These tests may be recommended every 2 to 5 years starting at age 25 or earlier, depending on family history.
• Pancreatic cancer screening. In people with a family history of pancreatic cancer, periodic screening for pancreatic cancer may be recommended starting at age 50 or starting at 10 years younger than the earliest age a family member was diagnosed with it.
• Prostate cancer screening. A PSA test may be recommended yearly starting at age 40.

Your exact screening plan may be adjusted based on your age and personal and family cancer histories. Because Li-Fraumeni syndrome is rare and screening planning is complex, care often is coordinated by a team with experience in inherited cancer syndromes.

治疗

There is no treatment for the TP53 gene change that causes Li-Fraumeni syndrome. Treatment focuses on treating any cancer that forms.

When planning cancer treatment, the healthcare team also thinks about how treatments might affect a person's future cancer risk. This may include:

• Choosing treatments other than radiation therapy. In a person with Li-Fraumeni syndrome, radiation therapy can increase the risk of a new cancer in the area that was treated. So healthcare teams may choose cancer treatments other than radiation. However, radiation therapy may still be recommended when the benefits outweigh the risks.
• Choosing mastectomy for breast cancer. As an example, for breast cancer treatment, mastectomy may be recommended instead of lumpectomy followed by radiation. Mastectomy may help avoid radiation treatment.

准备您的预约

It may help to take steps to prepare for your appointments.

What you can do

Before your appointment, it may help to gather information to bring with you.

• Collect and document your personal and family histories of cancer.
• If someone in your family has had genetic testing that found a TP53 gene change, try to get a copy of that person's genetic test report.

It also may help to prepare a list of questions ahead of time. For Li-Fraumeni syndrome, some basic questions to ask may include:

• What does my genetic test result mean for me?
• If my TP53 test result suggests mosaicism, do I need more testing?
• Should I meet with a genetic counselor?
• What is my risk of cancer?
• What cancer screening tests do I need, and how often do I need them?
• At what age should cancer screening start for me or my child?
• Are there imaging tests or treatments that use radiation that I should avoid or limit?
• Should I consider surgery to lower my risk of breast cancer?
• Are there research studies or clinical trials that I should think about?
• Should children or other family members have genetic testing?
• What are the chances that I will pass Li-Fraumeni syndrome on to my children?
• If I want to have children, what reproductive options are available to me?