Li-Fraumeni syndrome

Li-Fraumeni Syndrome: A Rare Cancer Predisposition Disorder

Li-Fraumeni syndrome (LFS) is a rare, inherited disorder that significantly increases the risk of developing several types of cancer, particularly in children and young adults [2][4]. This condition is characterized by an autosomal dominant pattern of inheritance, meaning that only one copy of the altered gene in each cell is sufficient to increase the risk of cancer development [3].

Key Features:

• Increased Cancer Risk: People with LFS are at a higher risk of developing various types of cancer, including osteosarcoma and soft tissue sarcoma, breast cancer, brain tumors, adrenocortical carcinoma, and leukemia [1][5].
• Hereditary Nature: Li-Fraumeni syndrome is inherited in an autosomal dominant pattern, meaning that it can be passed down from parents to children through a mutated gene [3].
• Rare Disorder: LFS is a rare condition, affecting only a small percentage of the population [4].

Cancer Types Associated with LFS:

• Osteosarcoma and soft tissue sarcoma
• Breast cancer (particularly in individuals AFAB)
• Brain tumors
• Adrenocortical carcinoma
• Leukemia

These cancers can occur at an early age, even in childhood, and are often aggressive and difficult to treat [5][13].

References:

[1] Li, F. P., & Fraumeni, J. F. (1969). Rhabdomyosarcoma in children: Epidemiologic study and identification of a familial cancer syndrome.

[2] Li-Fraumeni syndrome. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK1488/

[3] Autosomal dominant inheritance. (n.d.). Retrieved from https://ghr.nlm.nih.gov/primer/inheritance/autosomaldominant

[4] Li-Fraumeni syndrome. (n.d.). Retrieved from https://www.cancer.org/cancer/li-fraumeni-syndrome.html

[5] Li-Fraumeni syndrome. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK1488/

[13] Li–Fraumeni syndrome. (n.d.). Retrieved from https://en.wikipedia.org/wiki/Li%E2%80%93Fraumeni_syndrome

Diagnosing Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) can be diagnosed through a combination of clinical criteria and genetic testing.

• Clinical Criteria: The diagnosis of LFS is based on the presence of certain clinical features, such as:
  • A personal history of cancer at an early age (typically before 46 years old)
  • A family history of cancer in first-degree relatives (parents or siblings) with a similar pattern of cancers
  • Multiple primary cancers (more than one type of cancer diagnosed in the same individual)
• Genetic Testing: Genetic testing for LFS involves analyzing the TP53 gene to detect mutations. This test can be performed on:
  • Blood samples
  • Saliva samples

How is Li-Fraumeni Syndrome Diagnosed?

The diagnosis of LFS typically involves a multidisciplinary approach, including:

• Genetic Counseling: A genetic counselor will discuss the risks and benefits of genetic testing with you.
• Clinical Evaluation: A healthcare provider will assess your medical history and perform a physical examination to determine if you meet the clinical criteria for LFS.
• Genetic Testing: If recommended, a blood or saliva sample will be taken and sent to a lab for analysis of the TP53 gene.

What is Involved in Genetic Testing?

The genetic testing process typically involves:

1. Collecting a blood or saliva sample
2. Sending the sample to a laboratory for analysis
3. Analyzing the TP53 gene for mutations

References:

• [4] Li-Fraumeni syndrome (LFS) is diagnosed based on clinical criteria and/or genetic testing for the mutation in the TP53 gene.
• [8] If genetic testing is recommended, a blood or saliva sample will be taken and sent to a lab for analysis of the TP53 gene and other cancer susceptibility genes.
• [9] The NORD states that “Li-Fraumeni syndrome is diagnosed based on the presence of a so-called pathogenic or likely pathogenic variant in the TP53 gene;” further ...
• [12] If you or a family member meets criteria that indicate Li-Fraumeni syndrome or Li Fra

Differential Diagnoses for Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome, and its differential diagnoses include several other hereditary cancer syndromes. Some of the key differential diagnoses for LFS are:

• Hereditary Breast and Ovarian Cancer (HBOC) Syndrome: This syndrome is characterized by an increased risk of breast and ovarian cancers, similar to LFS.
• CHEK2 Cancer Susceptibility Syndrome: Also known as "Li-Fraumeni syndrome 2", this syndrome is associated with an increased risk of various types of cancer, including breast, colon, and prostate cancers.
• Constitutional Mismatch Repair Deficiency (CMMRD): This syndrome is characterized by a deficiency in the mismatch repair system, leading to an increased risk of various types of cancer.

Key Points

• Differential diagnoses for LFS include HBOC syndrome, CHEK2 cancer susceptibility syndrome, and CMMRD.
• Confirmation of reported family history is particularly important if LFS is in the differential diagnosis [7].
• Genetic testing can help differentiate between these syndromes and confirm a diagnosis of LFS [11].

References

[4] Differential diagnoses include hereditary breast and ovarian cancer syndrome, CHEK2 cancer susceptibility syndrome, and constitutional mismatch repair deficiency. [7] Confirmation of reported family history is particularly important if LFS is in the differential diagnosis. [11] Diagnosis Li-Fraumeni syndrome is diagnosed based on clinical criteria and/or genetic testing for the mutation in the TP53 gene.