Li Fraumeni syndrome
Li-Fraumeni Syndrome Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant hereditary disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults. It is associated with mutations in the TP53 gene, which plays a crucial role in regulating the cell cycle and preventing tumor formation.
Overview[edit | edit source]
Li-Fraumeni syndrome is characterized by a predisposition to a wide range of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, adrenocortical carcinoma, and leukemias. The syndrome was first described in 1969 by Dr. Frederick Li and Dr. Joseph Fraumeni, who observed a pattern of familial cancer clustering.
Genetics[edit | edit source]
The primary genetic cause of Li-Fraumeni syndrome is a germline mutation in the TP53 gene, located on chromosome 17p13.1. TP53 encodes the p53 protein, a crucial tumor suppressor that regulates the cell cycle and induces apoptosis in response to DNA damage. Mutations in TP53 lead to loss of function of the p53 protein, allowing cells with damaged DNA to proliferate unchecked.
Inheritance[edit | edit source]
Li-Fraumeni syndrome is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is sufficient to increase cancer risk. Individuals with LFS have a 50% chance of passing the mutation to their offspring.
Clinical Features[edit | edit source]
Individuals with Li-Fraumeni syndrome have a significantly increased risk of developing multiple primary cancers throughout their lifetime. The most common cancers associated with LFS include:
- Breast cancer: Often occurs at a younger age than in the general population.
- Soft tissue sarcomas: Such as rhabdomyosarcoma and leiomyosarcoma.
- Osteosarcomas: Bone cancers that typically occur in adolescence.
- Brain tumors: Including gliomas and medulloblastomas.
- Adrenocortical carcinoma: A rare cancer of the adrenal glands.
- Leukemias: Blood cancers, particularly acute lymphoblastic leukemia.
Diagnosis[edit | edit source]
Diagnosis of Li-Fraumeni syndrome is based on clinical criteria and genetic testing. The classic criteria include: 1. A sarcoma diagnosed before age 45. 2. A first-degree relative with any cancer before age 45. 3. Another first- or second-degree relative with any cancer before age 45 or a sarcoma at any age. Genetic testing for TP53 mutations can confirm the diagnosis.
Management[edit | edit source]
Management of Li-Fraumeni syndrome involves regular surveillance for early detection of cancers, as well as risk-reducing strategies. Surveillance may include:
- Annual whole-body MRI scans.
- Regular breast cancer screening, including MRI, starting at an early age.
- Routine dermatological exams.
Risk-reducing options may include prophylactic surgeries, such as mastectomy, to reduce the risk of breast cancer.
Prognosis[edit | edit source]
The prognosis for individuals with Li-Fraumeni syndrome varies depending on the types and stages of cancers that develop. Early detection and treatment of cancers can improve outcomes.
Research[edit | edit source]
Ongoing research aims to better understand the molecular mechanisms of TP53 mutations and to develop targeted therapies for cancers associated with Li-Fraumeni syndrome.
See Also[edit | edit source]
- TP53
- Cancer predisposition syndromes
- Genetic counseling
- Li, F. P., & Fraumeni, J. F. (1969). "Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?" Annals of Internal Medicine.
- Malkin, D. (2011). "Li-Fraumeni syndrome." Genes & Cancer.
NIH genetic and rare disease info[edit source]
Li Fraumeni syndrome is a rare disease.
Search WikiMD
Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro / Zepbound) available.
Advertise on WikiMD
WikiMD's Wellness Encyclopedia |
Let Food Be Thy Medicine Medicine Thy Food - Hippocrates |
Translate this page: - East Asian
中文,
日本,
한국어,
South Asian
हिन्दी,
தமிழ்,
తెలుగు,
Urdu,
ಕನ್ನಡ,
Southeast Asian
Indonesian,
Vietnamese,
Thai,
မြန်မာဘာသာ,
বাংলা
European
español,
Deutsch,
français,
Greek,
português do Brasil,
polski,
română,
русский,
Nederlands,
norsk,
svenska,
suomi,
Italian
Middle Eastern & African
عربى,
Turkish,
Persian,
Hebrew,
Afrikaans,
isiZulu,
Kiswahili,
Other
Bulgarian,
Hungarian,
Czech,
Swedish,
മലയാളം,
मराठी,
ਪੰਜਾਬੀ,
ગુજરાતી,
Portuguese,
Ukrainian
Medical Disclaimer: WikiMD is not a substitute for professional medical advice. The information on WikiMD is provided as an information resource only, may be incorrect, outdated or misleading, and is not to be used or relied on for any diagnostic or treatment purposes. Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition. WikiMD expressly disclaims responsibility, and shall have no liability, for any damages, loss, injury, or liability whatsoever suffered as a result of your reliance on the information contained in this site. By visiting this site you agree to the foregoing terms and conditions, which may from time to time be changed or supplemented by WikiMD. If you do not agree to the foregoing terms and conditions, you should not enter or use this site. See full disclaimer.
Credits:Most images are courtesy of Wikimedia commons, and templates Wikipedia, licensed under CC BY SA or similar.
Contributors: Prab R. Tumpati, MD