Hereditary Cancer Predisposition Program at the Cancer Center

Li-Fraumeni Syndrome

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome (LFS) is a rare hereditary condition that increases a person's risk for a wide spectrum of tumors. In LFS, the tendency to develop cancer is inherited, meaning that it can be passed from an affected parent to a child. There are several types of cancer that are commonly associated with Li-Fraumeni syndrome:

Some people with Li-Fraumeni syndrome develop other types of cancer:

In most cases, cancers associated with Li-Fraumeni syndrome develop in children or young adults, but they can occur during any stage of life. People with Li-Fraumeni syndrome are typically younger when they develop cancer compared to healthy individuals in the general population. People with Li-Fraumeni syndrome are also at increased risk for multiple cancers in their lifetimes.

What causes Li-Fraumeni syndrome?

Li-Fraumeni syndrome is caused by alterations, also known as mutations, at specific locations in an individual’s genetic information. Each of us has a large amount of genetic information that is organized into smaller segments known as “genes." Genes provide the necessary instructions that our cells require to perform their different functions within our bodies.

There is a specific gene known as TP53, located on chromosome 17, which is altered in patients with Li-Fraumeni syndrome. The normal role of the TP53 gene is to produce a protein that regulates cell growth and division. When both copies of this gene are altered within a cell, the affected cell can grow and divide in an abnormal fashion, which can ultimately lead to tumor formation.

How is Li-Fraumeni syndrome inherited?

With rare exceptions, each person has two copies of every gene, including TP53. In most cases, Li-Fraumeni syndrome is caused when an individual inherits one abnormal or “mutated” copy of the TP53 gene from an affected parent. A person carrying an alteration in one TP53 gene copy has a 50 percent (or 1 in 2) chance of passing this same alteration on to his or her future children. Children who inherit the altered gene copy have Li-Fraumeni syndrome and therefore are at increased risk to develop cancer.

Li-Fraumeni syndrome is commonly seen in several generations of an affected family. LFS does not skip generations. However, certain people found to carry an alteration in TP53 are the first ones in their family to have this genetic change. In this situation, a new mutation has occurred in one of the two TP53 gene copies carried by these individuals. The affected individuals can pass these new mutations in TP53 on to future generations.

How do you diagnose Li-Fraumeni syndrome?

A careful and detailed review of a person's medical and family history is important when attempting to make a diagnosis of Li-Fraumeni syndrome. A doctor or genetic counselor may construct a pedigree, or a multi-generation family tree, that shows which members of the family have developed cancer, the types of cancer, and their ages when the cancer first occurred. Some indicators suggesting a possible diagnosis of Li-Fraumeni syndrome in the family may include:

Several different classification schemes have been developed to aid in making a clinical diagnosis of Li-Fraumeni syndrome. The classic diagnostic criteria for LFS were defined in 1969 by Drs. Li and Fraumeni and include:

Approximately 70 percent of families meeting classic criteria for Li-Fraumeni syndrome carry mutations in the TP53 gene.

More recently, another set of criteria, known as the Chompret criteria, has been proposed to identify families who may not meet classic Li-Fraumeni syndrome diagnostic criteria but possibly still be affected:

It is estimated that at least 20 percent of families meeting Chompret criteria for LFS carry mutations in the TP53 gene.

Individuals who do not meet classic Li-Fraumeni syndrome or Chompret criteria, but nonetheless exhibit some features of LFS, may be diagnosed with Li-Fraumeni-like (LFL) syndrome. Two sets of diagnostic criteria for LFL syndrome have been proposed:

Birch definition of Li-Fraumeni-like syndrome:

Eeles definition of syndrome:

Approximately 22 percent of families meeting Birch or Eeles criteria for LFL syndrome carry mutations in the TP53 gene.

Even in cases where a family does not meet all of the diagnostic criteria for Li-Fraumeni syndrome, it may still be recommended that a person at risk undergo counseling and consider genetic testing to detect the presence of a TP53 gene alteration.

How do you test for Li-Fraumeni syndrome?

In order to confirm that a person has LFS, a genetic test must be completed. First, a blood or saliva sample is obtained from an affected individual with cancer. DNA is isolated from the sample and the two copies of the TP53 gene are evaluated by direct DNA sequencing. Sequencing is a process by which a person’s genetic code is compared to a “normal” reference code. In the case of Li-Fraumeni syndrome, the patient’s two copies of the TP53 gene are evaluated and compared to the normal reference sequence for TP53. If an alteration is identified, a genetic counselor can next examine whether the alteration has been previously reported in other individuals with LFS. TP53 genetic test results can provide important information for other family members. Knowing the specific alteration that is present in a person with cancer allows other family members to have testing to determine whether they also carry this alteration in the TP53 gene.

Options for people considering pregnancy

There are several options for an individual who is found to have an alteration in TP53 and who does not want to pass this alteration on to his or her future children:

Genetic tests for cancers not associated with Li-Fraumeni syndrome

It is possible that an individual may not have an alteration in TP53 despite having developed cancer(s) suggestive of Li-Fraumeni syndrome. In these cases, it is likely that other, as yet unknown, genes besides TP53 are responsible for the development of the cancers. Alterations in one other gene, known as CHEK2, were originally reported as a possible cause of Li-Fraumeni syndrome in a few families; however, more recent studies have revealed that CHEK2 mutations are unlikely to be a cause of Li-Fraumeni syndrome (Evans, Birch & Narod, 2008).

Things to consider before having genetic testing for Li-Fraumeni syndrome

Deciding to pursue genetic testing for Li-Fraumeni syndrome can be complex. Individuals who are found to have an altered TP53 gene may experience depression, anxiety, anger and fear of the future when they receive the test results. Family relationships can be affected both positively and negatively by this genetic information. There is also the possibility that a person who is found to have an altered TP53 gene could have more difficulty obtaining disability or life insurance from certain insurance companies. The decision to undergo TP53 genetic testing should be carefully considered and discussed thoroughly with a physician and/or genetic counselor before the testing takes place. Once results are available, they should be disclosed with the help of a genetic counselor.

What are the cancer risks in children and adults with Li-Fraumeni syndrome?

It is estimated that 50 percent of people with Li-Fraumeni syndrome will develop a cancer by age 30 and up to 90 percent will develop cancer by the time they are 60 years old. Men with LFS may have a lower lifetime risk of cancer compared to women with LFS. People with LFS are also at increased risk for developing multiple primary tumors and may be at increased risk for developing radiation-induced cancers. Unfortunately, it is hard to predict which cancers will develop in children and adults with TP53 mutations and when these cancers will occur. By undergoing regular check-ups and cancer screening tests, individuals at risk can ensure that cancers will be detected at their earliest and most treatable stages. It is also important that parents of children with TP53 mutations, and adults with TP53 mutations, be on the lookout for signs of illness that cannot otherwise be explained. Individuals should be evaluated promptly by their doctors if such signs develop, as these could be evidence of an underlying cancer.

Parents of a child with a cancer associated with Li-Fraumeni syndrome should consider the surveillance measures listed at, even if they decide not to pursue testing for TP53 mutations in their family.

What is the recommended cancer screening protocol for children?

For children, recommended surveillance measures include:

Other screening measures, which are currently under investigation, include:

Children should be encouraged to lead as healthy a lifestyle as possible. They should eat a balanced diet, avoid excess sun exposure and always wear sun block and a hat when outdoors in the sunlight. As adolescents, they should be discouraged from smoking cigarettes or cigars and should not be exposed to secondhand smoke. Parents should watch for symptoms of illness and have their children evaluated promptly if these occur.

What are the cancer screening protocols for adults?

Adults within the family should also pursue a healthy lifestyle, avoid tobacco use and excess alcohol consumption, use protective measures when in the sun and follow published guidelines for cancer surveillance, which include:

Meet Courtney Simmons

Courtney Simmons has Li-Fraumeni syndrome, as did her mother and sister. Courtney’s own fight began when her mother’s was ending, with a pain in her knee. At CHOP, an MRI revealed a mass, and then a biopsy showed Courtney had a malignant tumor. She gathered her strength to face her diagnosis, and made an incredible impression on her medical team at CHOP in the process. Get to know Courtney in this video about her experience.


Support and information resources for Li-Fraumeni syndrome

Clinical services

Adults who have Li-Fraumeni syndrome or who would like more information about Li-Fraumeni syndrome may contact the Medical Genetics Team at the Hospital of the University of Pennsylvania at 215-662-4740. Appointments can also be requested online at or by calling 1-800-789-PENN (7366).


American Cancer Society
1599 Clifton Rd. NE
Atlanta, GA 30329
Phone: 1-800-227-2345

275 Seventh Avenue
New York, NY 10001
Phone: 1-800-813-HOPE (1-800-813-4673) or 212-712-8400
Fax: 212-712-8495

National Cancer Institute
6116 Executive Boulevard
Room 3036A
Bethesda, MD 20892-8322
Phone: 1-800-4-CANCER (1-800-422-6237)

Li-Fraumeni Syndrome Association
50 South Main Street
Bellingham, MA 02019

Additional sources of information for Li-Fraumeni syndrome
National Library of Medicine Genetics Home Reference: Li-Fraumeni syndrome
Cancer.Net Guide to Li-Fraumeni syndrome: Cancer information from the American Society of Clinical Oncology
Li Fraumeni Syndrome Study at the National Cancer Institute

Evans, D.G., Birch, J., & S.A. Narod. (2008). Is CHEK2 a cause of Li-Fraumeni syndrome? Journal of Medical Genetics, 45, 63-64.

Reviewed by: Kim Nichols, MD, Kristin Zelley, MS
Date: September 2012

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Li-Fraumeni Syndrome: Courtney's Story

At 16, Courtney was no stranger to the way cancer changes lives. She had lost a sister to the disease, and her mother had been battling recurrences for 21 years. Now it was her turn to fight. Read Courtney's story.