What is Li-Fraumeni syndrome?

Updated: Nov 13, 2018
  • Author: ; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Li-Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome in which patients are predisposed to cancer. [1] Li-Fraumeni syndrome is characterized by the wide variety of cancer types seen in affected individuals, a young age at onset of malignancies, and the potential for multiple primary sites of cancer during the lifetime of affected individuals. The following are the criteria for classic Li-Fraumeni syndrome, Li-Fraumeni–like syndrome, and the Chompret criteria, which provide guidelines for consideration of TP53 genetic testing.

Classic Li-Fraumeni syndrome criteria are as follows [2] :

  • A proband diagnosed with a sarcoma before age 45 years and

  • A first-degree relative with any cancer diagnosed before age 45 years and

  • Another first- or second-degree relative with any cancer diagnosed before age 45 years or a sarcoma diagnosed at any age

Li-Fraumeni–like syndrome criteria are as follows:

  • Birch definition [3] : (1) a proband with any childhood cancer or sarcoma, brain tumor, or adrenocortical carcinoma diagnosed before age 45 years and  (2) a first- or second-degree relative with a typical Li-Fraumeni cancer (sarcoma, breast cancer, brain tumor, adrenocortical carcinoma, or leukemia) at any age and (3) a first- or second-degree relative with any cancer before age 60 years

  • Eels definition [4] : Two first- or second-degree relatives with Li-Fraumeni–related malignancies (sarcoma, breast cancer, brain tumor, leukemia, adrenocortical tumor, melanoma, prostate cancer, pancreatic cancer) at any age

Chompret criteria for Li-Fraumeni syndrome are as follows:

  • A proband who has (1) a tumor belonging to the Li-Fraumeni tumor spectrum (soft-tissue sarcoma, osteosarcoma, premenopausal breast cancer, brain tumor, adrenocortical carcinoma, leukemia, or bronchoalveolar lung cancer) before age 46 years and  (2) at least one first- or second-degree relative with a Li-Fraumeni tumor (except breast cancer if the proband has breast cancer) before age 56 years or with multiple tumors [5] or

  • A proband with multiple tumors (except multiple breast tumors), 2 of which belong to the Li-Fraumeni tumor spectrum and the first of which occurred before age 46 years [6] or

  • A proband who is diagnosed with adrenocortical carcinoma or choroid plexus tumor, irrespective of family history [7]

While most hereditary family cancer syndromes involve 1 or 2 specific tumor types, members of Li-Fraumeni syndrome kindreds are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft-tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma. Several other cancers have been seen at lower rates in Li-Fraumeni syndrome kindreds, including cancers of the lung, colorectum, stomach, prostate, ovary, and pancreas, as well as lymphoma, melanoma, and choroid plexus carcinoma. [8, 9]

Although osteosarcoma and chondrosarcomas occur frequently, no evidence suggests increased occurrence of Ewing sarcoma in association with Li-Fraumeni syndrome.


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