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Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults, such as soft tissue sarcoma, osteosarcoma, pre-menopause breast cancer, cerebral tumors, adrenocortical carcinoma (ACC) and leukemia. In addition a variety of other neoplasms can be developed. Multiple cancers and tumors linked to LFS are often produced in childhood or as young adults and the survivors have a greater risk of various primary cancers.

LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history. At least 70% of individuals diagnosed clinically have an identifiable germ line pathogenic variant in TP53, the only gene so far identified in which mutation is definitively associated with LFS.

It is difficult to estimate the incidence of this rare disease since its definition raises a problem of nosologic classification.

The most characteristic tumors are osteosarcomas, soft tissue sarcomas, breast cancer in young people, leukemia/ lymphoma, cerebral tumors and adenocarcinoma; however, any type of tumor can be observed.

The germ mutation of the TP53 gene is found in 70% of the families with LFS, as well as in some families or patients with patterns suggestive of the disease, even without strictly fulfilling the criteria. The risk of a carrier of a deleterious mutation on the TP53 gene of developing cancer is 15% at 15 years of age, 80% for women of 50 years and 40% for men of the same age. The significant difference between sexes can be explained almost completely owing to breast cancer. The risk of developing a second cancer, especially a radiation-induced type, is high.

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

A first-degree relative or second-degree relative, meaning a grandparent, aunt/uncle, niece/nephew, or grandchild, with any cancer before age 45 or a sarcoma at any age


  • TP53