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p53 gene- Li Fraumeni Syndrome (LFS)

Li-Fraumeni syndrome (LFS)

Li-Fraumeni syndrome is an extremely rare condition most commonly caused by mutations in the TP53 gene. Li-Fraumeni syndrome is a cancer predisposition syndrome associated with the development of the following classic tumors: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias.  Other cancers also seen at increased frequency are colorectal, lung, melanoma, prostate, pancreatic, and others. Mutations in this gene are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation. The majority of individuals with LFS inherit the condition from a parent; however, 20% of individuals have a new (de novo) mutation.

LFS is characterized by high penetrance, unusually young ages at cancer diagnosis, and frequent occurrence of multiple primary tumors. It is estimated that the lifetime risk developing of any cancer in an individual with LFS is 90%. Approximately 50% of these cancers will be diagnosed before age 30. In a retrospective study of 200 carriers of TP53 germline mutations who had a previous diagnosis of cancer, 15% developed a second, 4% a third and 2% developed a fourth cancer, with the highest risk of additional cancers in survivors of childhood malignancies.

The following recommendations have been suggested for individuals who have a clinical and/or genetic diagnosis of Li-Fraumeni Syndrome. These guidelines have been adapted from recommendations given by the NCCN Guidelines Version 1.2014.


Adrenocortical carcinoma

  • Ultrasound of abdomen and pelvis every 3–4 months
  • Complete urinalysis every 3–4 months
  • Blood tests every 4 months: β-human chorionicgonadotropin, alpha-fetoprotein, 17-OH-progesterone, testosterone, dehydroepiandrosterone sulfate, androstenedione

Brain tumor

  • Annual brain MRI

Soft tissue and bone sarcoma

  • Annual rapid total body MRI

 Leukemia or lymphoma

  • Blood test every 4 months: complete blood count, erythrocyte sedimentation rate, lactate dehydrogenase


 Breast cancer (women)

  • Monthly breast self-examination starting at age 18 years
  • Clinical breast examination twice a year, starting at age 20–25 years, or 5–10 years before the earliest known breast cancer in the family
  • Annual mammography and breast MRI screening starting at age 20–25 years, or at earliest age of onset in the family
  • Consider risk-reducing bilateral mastectomy

 Brain tumor

  • Annual brain MRI

Soft tissue and bone sarcoma

  • Annual rapid total body MRI
  • Ultrasound of abdomen and pelvis every 6 months

 Colon cancer

  • Colonoscopy every 2 years, beginning at age 40 years, or 10 years before the earliest known colon cancer in the family


  • Annual dermatological examination

Leukemia or lymphoma

  • Complete blood count every 4 months
  • Erythrocyte sedimentation rate, lactate dehydrogenase every 4 months

*In addition to regular assessment with family physician with close attention to any medical concerns or complaints.


Li-Fraumeni Syndrome Association

Li-Fraumeni Syndrome Support Group

CDD Conferences: Mutant p53 Toronto

Genetics Home Reference:

American Society of Clinical Oncology