Li Fraumeni Syndrome

Li Fraumeni Syndrome occurs mostly in patients who have a germline mutation or loss of function of TP53.


TP53 is an essential tumour suppressor gene that has roles in cell cycle arrest, response to DNA damage and apoptosis. If cells in the patient acquire a second hit on the normal TP53 gene, the cell loses a number of tumour suppressor functions and is more likely to develop malignancy.

Clinical Features

Aside from an increased risk of developing numerous cancers there are no clinical findings on examination to suggest the disorder.
The most common cancers seen in patients with Li Fraumeni are:

  • Breast cancer (in women)
  • Adrenal tumours
  • Brain tumours
  • Sarcomas

Classical Li Fraumeni is a clinical diagnosis made in patients who:

  • Present with sarcoma before the age of 45
  • Have a first degree relative with cancer before the age of 45
  • and an additional first degree or second degree relative
    • with cancer before the age of 45
    • or with sarcoma at any age

Suspect cases can also be identified using Chompret criteria (1st or 2nd degree relatives with similar tumours, multiple tumours, or adrenocortical tumours), or in patients who do not fulfill either criteria but have a suspicious presentation and family history of multiple tumours.
Testing for TP53 is usually positive in cases of true Li Fraumeni syndrome.


There is no specific screening policy for Li Fraumeni aside from a generally heightened awareness that cancers may occur and that patients and clinicians should be observant to try and achieve early detection.
Management of malignancy in patients with Li Fraumeni should consider that the risk of second malignancies induced by radiation may be increased. If radiotherapy is not essential for management then it should be avoided where possible (eg. mastectomy instead of lumpectomy + RT).