Li-Fraumeni Syndrome (LFS)

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome (LFS) is a rare condition that makes an affected person more likely to develop one or more cancers during his or her lifetime. It is usually inherited from a family member.

The most common cancers associated with LFS are:

• Soft tissue sarcoma
• Osteosarcoma
• Brain and central nervous system (CNS) tumors
• Adrenocortical carcinoma
• Acute leukemia
• Breast cancer

Less commonly, people with Li-Fraumeni syndrome develop other types of cancers, including:

• Melanoma
• Thyroid cancer
• Lung adenocarcinoma
• Digestive (esophagus, stomach, pancreas or colon) cancer
• Urinary (kidney, bladder) cancer
• Reproductive system (uterus, ovaries, prostate, gonads) cancer

LFS was first recognized in the 1969 by Frederick Li, MD, and Dr. Joseph Fraumeni, Jr., MD, while studying pediatric and familial cancers (cancers that run in families) at the National Cancer Institute.

What is the cancer risk for people with Li-Fraumeni syndrome?

Because of the wide range of cancer types that can affect children with Li-Fraumeni syndrome, it is hard to predict the kinds of cancer that will develop. It is also hard to know when these cancers will occur.

• By age 30, it is estimated that half (50%) of all people with Li-Fraumeni syndrome will develop some kind of cancer.
• By age 60, the likelihood of cancer for people with Li-Fraumeni syndrome increases to about 80%–90%.
• People with Li-Fraumeni syndrome are more likely to develop multiple cancers.

What causes Li-Fraumeni syndrome?

Li-Fraumeni syndrome is most often caused by changes in a gene known as TP53. About 70% of families with LFS will have a mutation in the TP53 gene. The mutation takes away the gene’s ability to function correctly. One of the main jobs of the TP53 gene is to prevent cancers from forming.

Not everyone with a TP53 gene mutation will develop cancer. But the risks are significantly higher than in the general population.

How is Li-Fraumeni syndrome diagnosed?

Li-Fraumeni syndrome may be suspected after looking at a person’s medical history or their family’s medical history. To get a history, a doctor or genetic counselor will ask questions about a person’s health and the health of other family members.

The genetic counselor or doctor will record which family members have developed cancers, along with the types of cancers and ages at which these cancers happened. From this information, the counselor or doctor will create a family tree and examine it to find out if:

• There are more cancers than normal.
• Cancers occurred at younger than expected ages.
• The types of cancers are associated with Li-Fraumeni syndrome.

If LFS is suspected, patients may choose to have a blood sample collected and sent for testing. Testing is always optional. DNA will be isolated from the cells. The TP53 gene will be checked for possible mistakes (also called mutations.) If a TP53 mutation is found, a genetic counselor will work with the family to find out if other family members should consider testing.

What is the general criteria for an LFS diagnosis?

Classic LFS is diagnosed when a person has all of the following criteria:

• A sarcoma diagnosed before age 45
• A first-degree relative (parent, sibling or child) with any cancer before age 45
• A first-degree relative or second-degree relative (grandparent, aunt/uncle, niece/nephew, or grandchild) with any cancer before age 45 or a sarcoma at any age

Another set of criteria that has been proposed to identify affected families beyond the classic criteria is called the Chompret Criteria for Clinical Diagnosis of Li-Fraumeni Syndrome. A diagnosis of LFS and performing TP53 gene mutation testing is considered for anyone with a personal and family history that meets 1 of 3 criteria:

• A tumor associated with LFS before the age of 46 and at least 1 first-degree or second-degree family member with an LFS-related tumor, except breast cancer. If the individual has breast cancer, it must have occurred before the age of 56 or with multiple tumors.
• A person with multiple tumors, except multiple breast tumors, 2 of which belong to the LFS tumor spectrum and at least 1 occurred before age 46
• A person who is diagnosed with adrenocortical tumor or a choroid plexus tumor, regardless of family history

Can Li-Fraumeni syndrome be treated?

At present, there is no way to correct the TP53 mutation associated with LFS. The cancers that result from the syndrome can usually be treated. It is typically recommended that radiation be avoided if possible.

Are there things people with Li-Fraumeni syndrome can do to prevent cancer?

People with Li Fraumeni are encouraged to adopt healthy lifestyle habits and have regular physical examinations and screenings.

Healthy lifestyle habits include:

• Eat a healthful diet with lots of fruits and vegetables
• Get regular exercise
• Limit sun exposure and always wear sunscreen and protective clothing (long sleeves, hat) 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

People with Li-Fraumeni syndrome should also watch closely for signs and symptoms that could signal cancer and report them promptly to their physician. These signs and symptoms include:

• Unexplained weight loss
• Loss of appetite
• Aches, pains, lumps or swellings that cannot be explained
• Headaches or changes in vision or nerve function that do not go away
• New moles or changes in moles that are already present

Parents of children with Li-Fraumeni syndrome should watch for signs and symptoms of illness and seek medical help if anything unusual appears.

People who suspect LFS are encouraged to bring it up with their health care provider. Since LFS is rare, some providers may not be aware of it.

Should people with LFS be screened for cancer?

It is recommended that children and adults with Li-Fraumeni syndrome be watched closely for possible cancer. The goal is to detect cancer at the earliest possible and most treatable stage. It is recommended that cancer screening tests be discussed with a doctor familiar with Li-Fraumeni syndrome.

Recommended cancer screenings:

Children (up to age 18)

• Complete physical exam every 3-4 months
• Prompt assessment with primary care physician for any medical concerns
• Adrenocortical tumor screening — Ultrasound of abdomen and pelvis every 3-4 months
  • In case of unsatisfactory ultrasound, blood tests every 3-4 months
• Brain cancer screening — Annual brain MRI (first MRI with contrast – thereafter without contrast if previous MRI normal with and no new abnormality)
• Soft tissue and bone sarcomas — Annual whole body MRI

Adults

• Complete physical exam every 6 months
• Prompt assessment with primary care physician for any medical concerns
• Breast cancer
  • Breast awareness (starting at age 18 years) – Report changes to a health care provider.
  • Clinical (by health care provider) breast exam twice a year (starting at age 20)
  • Annual breast MRI screening (ages 20-75) – ideally, alternating with annual whole body MRI (one scan every 6 months). MRI does not involve radiation.
• Brain tumor – Starting at age 18, annual brain MRI
• Soft tissue and bone sarcoma – Starting at age 18, Annual whole body MRI and ultrasound of abdomen and pelvis
• Gastrointestinal cancer – Beginning at age 25, upper endoscopy and colonoscopy every 2-5 years
• Melanoma – Beginning at age 18, annual skin examination

How common is Li-Fraumeni syndrome?

It is challenging to estimate the frequency of LFS.

In the U.S., one registry of Li-Fraumeni syndrome patients suggests that about 400 people from 64 families have this disorder, according to the National Library of Medicine’s Genetics Home Reference.

There are likely more than 1,000 multigenerational families worldwide with LFS, according to the Li Fraumeni Syndrome Association.

If I have Li-Fraumeni syndrome, will my child have it?

People with Li-Fraumeni syndrome have 1 in 2 or 50% chance of passing it on to their children.

Should I consider testing for me or my child?

The decision to test is a personal one. People considering TP53 genetic testing are strongly encouraged to receive professional genetic counseling before making a decision.

Testing a child in a family with LFS is a complex situation since the decision must be made by the child’s parents, with the help of the care team. Counseling can also help with the emotional effects that may occur when people learn that they are a carrier.

If cost of testing is a concern, many genetic testing companies can provide financial assistance for genetic testing costs. Genetic counselors can help patients find information about these services.

How do I pay for Li-Fraumeni related care?

Since LFS is so rare, many people in the health care industry, including some physicians, are not familiar with health care recommendations for patients. This may mean some costs associated with LFS are not covered by insurance companies.

The Li-Fraumeni Syndrome Association has a list of resources that may be helpful for families.

Questions to ask the health care team

Consider asking the following questions:

• What is my risk of developing cancer?
• Should I consider genetic testing?
• How can I find a genetic counselor?
• What can I do to reduce my risk of cancer?
• What are my options for cancer screening and prevention?
• Does my family history increase my risk of cancer?
• Could members of my family have LFS?
• Will you refer me to a hereditary cancer clinic to meet with a genetic counselor and other genetics specialists?
• Should my child's cancer care change if he or she is diagnosed with LFS?

Other resources

Related Content