Syndrome which is associated with increased risk of leukaemia:
**Core Concept**
Li-Fraumeni syndrome is a rare genetic disorder characterized by an increased risk of developing various cancers, including leukemia, due to mutations in the TP53 tumor suppressor gene. This syndrome is an example of a germline mutation, which can be inherited from one's parents.
**Why the Correct Answer is Right**
Li-Fraumeni syndrome is associated with a high risk of leukemia due to the loss of function of the TP53 gene, which plays a crucial role in regulating the cell cycle and preventing uncontrolled cell growth. The TP53 protein acts as a tumor suppressor by repairing DNA damage, arresting cell growth, and initiating apoptosis in damaged cells. In Li-Fraumeni syndrome, the mutation in the TP53 gene leads to a loss of its tumor suppressor function, increasing the risk of cancer development, including leukemia.
**Why Each Wrong Option is Incorrect**
**Option A:** Not a recognized genetic syndrome associated with an increased risk of leukemia.
**Option B:** Ataxia-telangiectasia is a genetic disorder that increases the risk of cancer, but it is not specifically associated with leukemia. It is characterized by a defect in the ATM gene, which plays a role in DNA repair.
**Option C:** Fanconi anemia is a genetic disorder that increases the risk of leukemia, but it is not the same as Li-Fraumeni syndrome. It is characterized by a defect in the FANCA gene, which plays a role in DNA repair.
**Clinical Pearl / High-Yield Fact**
Li-Fraumeni syndrome is often associated with a family history of cancer, particularly breast cancer, sarcomas, and brain tumors. A high index of suspicion for this syndrome should be maintained in patients with a strong family history of cancer.
**Correct Answer:** A. Li-Fraumeni syndrome