IllnessLi-Fraumeni syndrome, differential diagnosis

NGS +

[Sanger]

Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, especially in children and young adults. These cancers include breast cancer, osteo- and soft tissue sarcomas, brain tumors, leukemias and adrenocortical carcinomas. Other cancers are also more common. Li-Fraumeni syndrome is inherited in an autosomal dominant manner. A very similar disorder, called Li-Fraumeni-like syndrome, has many of the features mentioned above. Li-Fraumeni syndrome is associated with mutations in the tumor suppressor gene TP53. Nearly 75% of families with the classic syndrome and about 25% with Li-Fraumeni-like syndrome have germline mutations in this gene. De novo mutations occur in 7-20% of cases. Other genetic and environmental factors also likely influence the cancer risk in Li-Fraumeni syndrome. Which genetic factors play a role in these cases is unclear. The genes for DNA mismatch repair, breast/ovarian cancer and CHEK2 are the most important differential diagnoses. In families characterised according to the strictest criteria, TP53 mutations are detected in 80% of cases. A negative TP53 test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1311/

• Alias: Sarcoma family syndrome (<45 years)...
• ...osteosarcomas, breast/brain tumors, leukemia, adrenocortical carcinoma
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Lessel-Kubisch syndrome (MDM2)
• Accelerated tumor formation, susceptibility to (MDM2)
• Adrenocortical carcinoma, pediatric (TP53)
• Allelic: Fanconi anemia, complementation group D1 (BRCA2)
• Allelic: Fanconi anemia, complementation group S (BRCA1)
• Basal cell carcinoma 7 (TP53)
• Breast + colorectal cancer, susceptibility to (CHEK2)
• Breast cancer, male, susceptibility to (BRCA2)
• Breast cancer, somatic (TP53)
• Breast cancer, susceptibility to (CHEK2)
• Breast-ovarian cancer, familial, 1 (BRCA1)
• Breast-ovarian cancer, familial, 2 (BRCA2)
• Choroid plexus papilloma (TP53)
• Colorectal cancer (TP53)
• Colorectal cancer, hereditary nonpolyposis, type 1 (MSH2)
• Colorectal cancer, hereditary nonpolyposis, type 2 (MLH1)
• Colorectal cancer, hereditary nonpolyposis, type 4 (PMS2)
• Colorectal cancer, hereditary nonpolyposis, type 5 (MSH6)
• Endometrial cancer, familial (MSH6)
• Glioblastoma 3 (BRCA2)
• Glioma susceptibility 1 (TP53)
• Hepatocellular carcinoma, somatic (TP53)
• Li-Fraumeni syndrome (CHEK2, TP53)
• Medulloblastoma (BRCA2)
• Melanoma + neural system tumor syndrome (CDKN2A)
• Melanoma, cutaneous malignant, 2 (CDKN2A)
• Melanoma-pancreatic cancer syndrome (CDKN2A)
• Mismatch repair cancer syndrome 1 (MLH1)
• Mismatch repair cancer syndrome 2 (MSH2)
• Mismatch repair cancer syndrome 3 (MSH6)
• Mismatch repair cancer syndrome 4 (PMS2)
• Muir-Torre syndrome (MLH1, MSH2)
• Nasopharyngeal carcinoma, somatic (TP53)
• Osteosarcoma (TP53)
• Osteosarcoma, somatic (CHEK2)
• Pancreatic cancer 2 (BRCA2)
• Pancreatic cancer, somatic (TP53)
• Pancreatic cancer, susceptibility to, 4 (BRCA1)
• Prostate cancer (BRCA2)
• Prostate cancer, familial, susceptibility to (CHEK2)
• Wilms tumor (BRCA2)