Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease that affects young patients and consists of a predisposition to develop a wide range of tumors. Its pattern of inheritance is autosomal dominant.

In 70% of families affected by the disease, as well as in patients with disease patterns suggestive of the syndrome, germline mutations have been identified in the TP53 gene that codes for a nuclear transcription factor essential in the cellular response to DNA damage. TP53 is one of the major tumor suppressor genes.

The prevalence of LFS is estimated to be 1 case per 3,555-5,476 individuals.

Li-Fraumeni syndrome increases the risk of various tumors that can occur early in life and throughout life. The most characteristic tumors are osteosarcomas, soft tissue sarcomas, breast cancer, leukemias/lymphomas, brain tumors (such as glioblastomas and astrocytomas), adrenal carcinomas and colorectal cancer; however, any type of tumor can be seen.

The risk of developing cancer for a patient carrying a deleterious mutation in the TP53 gene is 15% at 15 years of age, 80% for women aged 50 years, and 40% for men of the same age; the significant difference between sexes is almost entirely explained by breast cancers. The risk of developing a second cancer, especially radiation-induced cancer, is high.

Children and adults with pathogenic TP53 mutations should have a complete annual physical examination, including dermatological examination and neurological examinations.Close attention should be paid to persistent symptoms, particularly headaches, bone pain, or abdominal discomfort and seek medical evaluation.Women should follow a breast cancer prevention program beginning at age 20-25. Screening for early detection of colorectal cancer is also recommended, with colonoscopies every two or three years, starting no later than age 25. In addition, exposure to diagnostic and therapeutic radiation should be minimized or avoided whenever possible, as well as exposure to carcinogens. Protection from ultraviolet radiation from the sun, avoiding smoking, avoiding occupational exposure to carcinogens, and minimizing alcohol consumption are important. The family should receive genetic counseling for the detection and follow-up of carriers of TP53 mutations.