Li-Fraumeni Syndrome

It is an autosomal dominant pathology characterized by an increased risk of developing different types of cancer at early ages. It is caused by alterations in the TP53 gene which is one of the main tumor suppressor genes.

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.

Disease management

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.

Genes analyzed



de Andrade KC, Khincha PP, Hatton JN, et al. Cancer incidence, patterns, and genotype-phenotype associations in individuals with pathogenic or likely pathogenic germline TP53 variants: an observational cohort study. Lancet Oncol. 2021 Dec;22(12):1787-1798.

Kennedy MC, Lowe SW. Mutant p53: it's not all one and the same. Cell Death Differ. 2022 May;29(5):983-987.

Schneider K, Zelley K, Nichols KE, et al. Li-Fraumeni Syndrome. 1999 Jan 19 [updated 2019 Nov 21]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

Vieira IA, Andreis TF, Fernandes BV, et al. Prevalence of the Brazilian TP53 Founder c.1010G>A (p.Arg337His) in Lung Adenocarcinoma: Is Genotyping Warranted in All Brazilian Patients? Front Genet. 2021 Feb 2;12:606537.

Front Genet.

Xu J, Qian J, Hu Y, et al. Heterogeneity of Li-Fraumeni syndrome links to unequal gain-of-function effects of p53 mutations. Sci Rep. 2014 Feb 27;4:4223.


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