Li-Fraumeni syndrome (LFS) is a syndrome that predisposes individuals to develop several types of benign and malignant tumors. In childhood, this most often includes:
- Choroid plexus carcinoma, a type of brain tumor
- Adrenocortical carcinomas, which is present in the adrenal glands located on top of the kidneys
- Osteosarcomas, or bone tumors
- Rhabdomyosarcomas, or soft tissue tumors
What are the causes?
LFS is caused by genetic changes that occur in the TP53 gene, which is often called the guardian of the genome and has several vital functions, including preventing tumor development and controlling the cell cycle. In 7 to 20% of cases, LFS may occur on its own, without being passed down from either parent. However, in most cases, genetic alterations, or changes in the TP53 gene that cause LFS, are inherited from one parent. This means that a patient’s full siblings also have a 50% chance of having Li-Fraumeni syndrome.
Not everybody with LFS will develop cancer in childhood, though almost 100% of women and 85 to 90% of men with this syndrome will go on to develop cancer in their lifetime. In large groups of patients with LFS, 22% received a cancer diagnosis by age 5 and 40% developed their first cancer by age 18.
How is Li-Fraumeni syndrome diagnosed?
Diagnosis of LFS occurs through genetic testing, which is often facilitated by a genetic counselor or a clinical oncology team.
Treatment and monitoring
Due to the increased risk of cancer, monitoring is recommended for both children and adults with LFS. This is best done at a center where physicians, genetic counselors and geneticists have expertise in LFS.
A diagnosis of LFS may change treatment plans for existing cancers, as well as the medical management and future surveillance or monitoring plans, as individuals with LFS are extremely sensitive to radiation and are at an increased risk for secondary cancers.
Research has shown that patients with LFS who undergo regular surveillance have a significantly higher overall survival (OS) than those who do not undergo regular surveillance.
Who is at risk?
Once an individual has been identified as having LFS, all family members at risk may choose to pursue genetic counseling and testing. A genetic counselor can help identify family members who may be at risk for LFS.