Li–Fraumeni syndrome

Autosomal dominant - en

Li–Fraumeni syndrome (LFS) is a rare, autosomal dominant hereditary disorder that predisposes individuals to a wide range of cancers. The syndrome is named after Dr. Frederick Li and Dr. Joseph Fraumeni, who first described it in 1969. Individuals with LFS have a significantly increased risk of developing multiple primary cancers, often at a young age.

Genetics

Li–Fraumeni syndrome is primarily associated with mutations in the TP53 gene, which encodes the p53 protein, a crucial tumor suppressor. The p53 protein plays a vital role in regulating the cell cycle and preventing genomic mutations. Mutations in the TP53 gene lead to a loss of function of the p53 protein, resulting in uncontrolled cell division and an increased risk of cancer.

Clinical Features

Individuals with Li–Fraumeni syndrome are at a higher risk for several types of cancer, including:

• Breast cancer
• Osteosarcoma (bone cancer)
• Soft tissue sarcoma
• Leukemia
• Brain tumors
• Adrenocortical carcinoma

The syndrome is characterized by the early onset of these cancers, often before the age of 30. Family history is a critical component in diagnosing LFS, as the syndrome follows an autosomal dominant inheritance pattern.

Diagnosis

Diagnosis of Li–Fraumeni syndrome typically involves a combination of clinical criteria and genetic testing. The classic criteria for LFS diagnosis include:

• A proband with a sarcoma diagnosed before age 45
• A first-degree relative with any cancer before age 45
• 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 and Surveillance

Management of Li–Fraumeni syndrome involves regular and comprehensive cancer screening to detect tumors at an early, more treatable stage. Recommended surveillance strategies include:

• Annual whole-body MRI
• Regular breast cancer screening starting at an early age
• Routine dermatological exams
• Regular blood tests and imaging studies for early detection of other cancers

Prognosis

The prognosis for individuals with Li–Fraumeni syndrome varies depending on the types and stages of cancers they develop. Early detection and treatment are crucial for improving outcomes. Genetic counseling is recommended for affected families to understand the risks and implications of the syndrome.

Related Pages

• TP53
• Breast cancer
• Osteosarcoma
• Soft tissue sarcoma
• Leukemia
• Brain tumors
• Adrenocortical carcinoma