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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:
Less commonly, people with Li-Fraumeni syndrome develop other types of cancers, including:
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.
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.
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.
Normally, cells carry 2 working copies of TP53. One is inherited from a person’s mother and one from the father. Cells from people with Li-Fraumeni syndrome carry 1 working copy of TP53 and one copy that is altered, or mutated.
When the remaining working copy of TP53 becomes damaged within a cell, this can lead to a cancer.
Most children with LFS inherit the syndrome from a parent who also has it. But some children with LFS may have a new (de novo) TP53 mutation that did not come from a parent. In these cases, the TP53 mutation either arose in an egg or sperm cell that formed the child or in one of the child’s cells during pregnancy. These children are the first in their families to have LFS.
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:
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 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.
Classic LFS is diagnosed when a person has all of the following criteria, according to the American Society of Clinical Oncology:
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:
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.
There is some evidence that a TP53 genetic mutation can cause a person to have an increased chance of developing cancer when exposed to radiation. It is recommended that patients avoid or minimize having X-rays, CT scans, or radiation therapy for cancer treatment when possible.
People with Li Fraumeni are encouraged to adopt healthy lifestyle habits and have regular physical examinations and screenings.
Healthy lifestyle habits include:
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:
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.
It is not yet known for certain whether monitoring for cancer in Li-Fraumeni syndrome patients is helpful. But increasing evidence suggests that this is the case, according to the American Society of Clinical Oncology.
As a result, it is recommended that children and adults with Li-Fraumeni syndrome should 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, according to the Li-Fraumeni Syndrome Association:
Children (up to age 18)
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.
People with Li-Fraumeni syndrome have 1 in 2 or 50% chance of passing it on to their children.
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.
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.
Consider asking the following questions:
Academic papers/ studies supporting recommended screenings: