Li-Fraumeni syndrome (LFS)
Li-Fraumeni syndrome is an extremely rare condition most commonly caused by mutations in the TP53 gene. Li-Fraumeni syndrome is a cancer predisposition syndrome associated with the development of the following classic tumors: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias. Other cancers also seen at increased frequency are colorectal, lung, melanoma, prostate, pancreatic, and others. Mutations in this gene are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation. The majority of individuals with LFS inherit the condition from a parent; however, 20% of individuals have a new (de novo) mutation.
LFS is characterized by high penetrance, unusually young ages at cancer diagnosis, and frequent occurrence of multiple primary tumors. It is estimated that the lifetime risk developing of any cancer in an individual with LFS is 90%. Approximately 50% of these cancers will be diagnosed before age 30. In a retrospective study of 200 carriers of TP53 germline mutations who had a previous diagnosis of cancer, 15% developed a second, 4% a third and 2% developed a fourth cancer, with the highest risk of additional cancers in survivors of childhood malignancies.
The following recommendations have been suggested for individuals who have a clinical and/or genetic diagnosis of Li-Fraumeni Syndrome. These guidelines have been adapted from recommendations given by the NCCN Guidelines Version 1.2014.
Children
Adrenocortical carcinoma
Brain tumor
Soft tissue and bone sarcoma
Leukemia or lymphoma
Adults
Breast cancer (women)
Brain tumor
Soft tissue and bone sarcoma
Colon cancer
Melanoma
Leukemia or lymphoma
*In addition to regular assessment with family physician with close attention to any medical concerns or complaints.
Resources
Li-Fraumeni Syndrome Association http://www.lfsassociation.org
Li-Fraumeni Syndrome Support Group http://www.mdjunction.com/li-fraumeni-syndrome
CDD Conferences: Mutant p53 Toronto http://www.cddconferences.eu/mutant-p53-toronto/
Genetics Home Reference: http://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome
American Society of Clinical Oncology http://www.cancer.net/cancer-types/li-fraumeni-syndrome