What is Li-Fraumeni syndrome (Li-Fraumeni syndrome, a rare genetic disorder)?

From the Guidelines

Li Fraumeni syndrome is a rare inherited condition that greatly increases a person's risk of developing multiple types of cancer throughout their lifetime, often at unusually young ages, and is caused by mutations in the TP53 gene. This condition is characterized by a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors 1. People with Li Fraumeni syndrome commonly develop breast cancer, brain tumors, bone cancers, soft tissue sarcomas, adrenal gland cancers, and leukemia, though many other cancer types can occur. The syndrome typically runs in families, with a 50% chance of passing it to children.

Key Features of Li Fraumeni Syndrome

• Caused by mutations in the TP53 gene, which normally acts as a tumor suppressor by preventing cells with damaged DNA from dividing 1
• High lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors 1
• Commonly develops breast cancer, brain tumors, bone cancers, soft tissue sarcomas, adrenal gland cancers, and leukemia
• Typically runs in families, with a 50% chance of passing it to children

Management and Screening

• Management involves intensive cancer screening starting in childhood, including regular physical exams, blood tests, ultrasounds, MRIs, and other imaging studies 1
• Annual breast MRI at age 20–75, and clinical breast examination every 6–12 months starting from age 20–25 are recommended for individuals with Li Fraumeni syndrome 1
• Genetic counseling is important for affected families to understand inheritance patterns and testing options
• Lifestyle modifications like avoiding radiation exposure when possible, maintaining a healthy weight, limiting alcohol, and not smoking may help reduce cancer risks.

From the Research

What is Li Fraumeni Syndrome

• Li Fraumeni syndrome (LFS) is a rare autosomal dominant familial cancer syndrome caused by germline mutations of the tumor protein p53 gene (TP53) 2, 3, 4.
• It is a hereditary cancer predisposition disorder that increases the risk of developing various types of cancer, including sarcomas, leukemia, breast malignancies, brain tumors, and adrenocortical cancers 2, 3, 5.

Types of Cancer Associated with LFS

• The most common types of cancer found in families with LFS include:
  • Sarcomas (such as osteosarcoma and rhabdomyosarcoma) 2, 3
  • Leukemia 2, 3
  • Breast malignancies 2, 3, 6
  • Brain tumors 2, 3
  • Adrenocortical cancers 2, 3
• Patients with LFS are also at increased risk of developing early-onset gastric and colon cancers, as well as cancers involving the thyroid, lungs, ovaries, and skin 2.

Diagnosis and Screening

• The diagnosis of LFS is usually confirmed by genetic testing for the identification of TP53 mutations 3, 4.
• Whole-body MRI is the preferred modality for annual screening of patients with LFS 2.
• Guidelines have been established for screening and managing patients with LFS, including recommendations for radiation-induced cancer risk reduction 2.

Cancer Risk and Prognosis

• The lifetime risk of cancer in individuals with LFS is greater than 70% in males and greater than 90% in females 2.
• Some patients with LFS develop multiple primary cancers during their lifetime 2.
• The occurrence of certain cancer subtypes, such as HER2+ breast cancer, may be more common in patients with LFS than in the general population 6.