Li-Fraumeni syndrome

Hereditary cancer syndrome with increased predisposition to early onset of many malignancies.

Autosomal dominant disorder linked with the germline mutations in the tumor suppressor gene TP53.

TP53 germline mutation loss of heterozygosity in cancer cells, resulting in no expression of functional TP 53 and is the presumed mechanism of transformation from normal to malignant cells.

Malignancies associated include sarcomas, breast cancer, brain tumors, adrenocortical carcinomas, and leukemias.

1-3% develop adrenal cortical cancers.

Incidence estimated to be 1 in 5000 live births worldwide.

70% of classic families have germline mutations, in tumor protein p53 and chromosome 17p13.

Recent associated malignancies expanded to include gastrointestinal cancers, endocrine neoplasms, and lymphomas.

Patients who survive one cancer have increased risk of developing additional malignancies.

Classically diagnosis of a sarcoma made in the proband patient before age 45 years, a first degree relative with a malignancy diagnosed before the age of 45 years and another first degree relative with a soft tissue or osteosarcoma before the age of 45.

Women who develop breast cancer before the age of 35 years and do not carry BRCA mutations should be tested for this syndrome.

The risk of developing cancer in individuals with p53 mutations estimated to be 50% by age 30 years and 90% by age 60 years.

Lifetime risk for cancer is up to 90%.

Follow-up of original study families showed an increases relative risk for cancer of 21.1 from ages 0-19 years, 6.2 from 20-44 years, and 2.4 from 45-59 years, as compared to the general population (Garber JE et al).

Osteosarcomas the second most common cancer seen in patients with this syndrome, with an incidence of 12%.

Malignancies can occur at any age and in any site preventing an adequate screening program.

Leukemia, lung cancer, colon cancer, melanoma frequently seen in families with Li-Fraumeni syndrome.

Kindreds Li-Fraumeni-like have cancer histories that are less prominent and have a 30% chance of carrying a germline p53 mutation.

Classic LFS TP53 germ line mutations are found in 70% of cases.

TP53 missense mutations or other changes in TP53 interfere with recognition and repair of genetic damage, allowing cancer cells to propagate.

Most cases have an onset of cancer as children or adolescents.

Children may present with virilization and elevated cortisol levels associated with adrenocortical tumors as the only manifestation of the syndrome.

Worldwide 400 families have been affected by LFS.

Patients with childhood cancers including sarcomas, brain tumors, and adrenal cortical tumors should be tested for T p53 gene.

All first-degree relatives of patients with this syndrome should have genetic testing.

All patients with the syndrome should undergo physical examination every 6-12 months including whole body and brain MRI, dermatological and neurological evaluations and blood tests for thyroid and adrenal functions and cancer markers.

Patients with this syndrome should undergo colonoscopy and breast cancer screening at an earlier age than in the general population.

Leave a Reply

Your email address will not be published. Required fields are marked *