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Li Fraumeni Syndrome

Li Fraumeni Syndrome

Li Fraumeni Syndrome

Li Fraumeni Syndrome

Li Fraumeni Syndrome

Li Fraumeni Syndrome



Li Fraumeni Syndrome

Li-Fraumeni Syndrome

Overview

What is Li-Fraumeni syndrome?

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome. This means that a person who has LFS will have an increased risk of developing cancer. The most common types of cancer found in families with LFS include osteosarcoma (bone cancer), soft tissue sarcoma, leukemia, breast cancer, brain cancer, and adrenal cortical tumors. An increased risk for melanoma, Wilms' tumor (a type of kidney cancer), and cancers of the stomach, colon, pancreas, esophagus, lung, and gonadal germ cells have also been reported. Almost every part of the body may be at risk for cancer in someone who has LFS.

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What causes LFS syndrome?

LFS and LFL are genetic conditions. This means that the cancer risk can be passed from generation to generation in a family. Approximately 70% of families with LFS will have a mutation (alteration) in the p53 gene. Mutations in the p53 gene are also found in 22% of families who have LFL by definition 1 and 8% of families who have LFL by definition 2. Mutations in another gene, called CHEK2, have been found in some families with LFS. It is not known if the cancer risks are the same in families that have p53 mutations and CHEK2 mutations. Research is ongoing to identify other genes associated with LFS and LFL.

How is LFS inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. LFS follows an autosomal dominant inheritance pattern. That means that even if a mutation happens in only one of the two copies of the gene, that person will have the increased cancer risk. Parents with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation; there is now a way to control this random, natural process. Therefore, a child who has a parent with a mutation has a 50% chance of naturally inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

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How common is LFS?

LFS is very rare. It is estimated that less than 400 families have been diagnosed with LFS worldwide. LFL is also considered to be rare.

How is LFS diagnosed?

Currently, both LFS and LFL are diagnosed on a clinical basis. This means that if a family history meets the LFS definition listed above, the family is considered to have LFS. The same is true for LFL. If a family history meets one of the two LFL definitions, the family is considered to have LFL.
It is possible to test for p53 mutations with a blood test. However, not all families with LFS will have a p53 mutation. At this time, testing for CHEK2 mutations is only available through research studies (clinical trials).

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What are the estimated cancer risks associated with LFS?

Individuals with LFS have up to a 50% chance of developing cancer by age 40 and a 90% chance to develop cancer by age 60. Breast cancer appears to be the greatest risk for women. However, less than 1% of all breast cancer is thought to be related to LFS.

Individuals with LFS also have a high risk of developing multiple cancers during their lifetime. One study showed that 15% of individuals with LFS had a second cancer, 4% had a third cancer, and 2% had a fourth cancer. However, some people with LFS will never develop cancer.
It is not known if the cancer risks in LFS and LFL are similar.

What are the screening options for LFS?

Due to the large variety of cancers associated with LFS and LFL and the limitations in screening for some of these cancers, there are almost no standard screening measures for LFS that are proven to increase early detection of cancer. One exception may be breast cancer screening. For this reason, people at risk for LFS or LFL (and their doctors) should pay careful attention to any unusual or lingering symptoms or illnesses, especially headaches, bone pain, or abdominal pain.

It is important to discuss with your doctor the following screening options, as each person is different:

Annual screening for children at risk

  • Complete physical examination
  • Complete blood count
  • Urinalysis (examination of urine)
  • Abdominal ultrasound
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