What is Li-Fraumeni syndrome?
What is Li-Fraumeni syndrome?
(lee-FRAH-meh-nee SIN-drome) A rare, inherited disorder that is caused by mutations (changes) in the TP53 gene. Having Li-Fraumeni syndrome increases the risk of developing many types of cancer. Cancers often develop at an early age, and more than one type of cancer may occur in the same person.
What causes Li-Fraumeni syndrome?
Li-Fraumeni syndrome is caused by an inherited (germline) pathogenic variant of the TP53 tumor suppressor gene on chromosome 17. LFS was first recognized in 1969, and in 1979, TP53 was identified in the tumor tissue of more than 50% of all cancer patients.
What are the symptoms of Li-Fraumeni syndrome?
People with Li-Fraumeni syndrome should also watch closely for symptoms that could signal cancer, such as:
- 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.
Why is Li-Fraumeni syndrome autosomal dominant?
Li-Fraumeni syndrome (LFS) is inherited in an autosomal dominant manner. This means that a person only needs a change ( mutation ) in one copy of the responsible gene in each cell to have LFS. In some cases, an affected person inherits the mutation from an affected parent.
How do you test for Li-Fraumeni syndrome?
Li-Fraumeni syndrome is diagnosed based on clinical criteria and/or genetic testing for the mutation in the TP53 gene….Classic LFS is diagnosed when a person has all of the following criteria:
- A sarcoma diagnosed before age 45.
- A first-degree relative, meaning a parent, sibling or child, with any cancer before age 45.
What is the life expectancy of someone with Lynch syndrome?
Table 1
| Disease | Location | Life expectancy |
|---|---|---|
| 20%–40% | ||
| Lynch syndrome | 2p, 3p, | Reduced |
| 2q, 7p | 60% | |
| 10% |
Can Li-Fraumeni skip a generation?
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.
How is Li-Fraumeni inherited?
Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing cancer. Most people with Li-Fraumeni syndrome inherit an altered copy of the gene from an affected parent .
What cancers are associated with Li-Fraumeni syndrome?
The most common types of cancer found in families with LFS include osteosarcoma (bone cancer), soft tissue sarcoma, acute leukemia, breast cancer, brain cancer, and adrenal cortical tumors, which involves an organ on the top of the kidney.
Which cancers are associated with Li-Fraumeni syndrome?
Does everyone have the TP53 gene?
Everyone has two copies of the TP53 gene, which we randomly inherit from each of our parents. Mutations in one copy of the TP53 gene can increase the chance for you to develop certain types of cancer in your lifetime. People with TP53 mutations have Li-Fraumeni syndrome (LFS).
Is there a syndrome similar to Li Fraumeni?
A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.
Is there a link between Li Fraumeni and CHEK2?
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).
What are the chompret criteria for Li Fraumeni?
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 may still be affected:
Which is a dominant negative mutation in Li Fraumeni syndrome?
Dominant Negative Mutations: Most individuals with Li–Fraumeni syndrome are heterozygous for a mutant TP53 gene, and some p53 mutants can inhibit the function of the wild-type p53 in a dominant negative manner.
