A 4-year-old child presented to the OPD with a palpable abdominal mass in the right flank region which was painless and slowly increasing in size along with some episodes of fever and hematuria. On examination, hypeension was noted. CT scan of the abdomen was done. The patient was operated and the mass was resected. The gross specimen and the HPE examination are given below. All of the following genes can be mutated in the above disease except: –

**Core Concept**
Wilms tumor, also known as nephroblastoma, is a malignant renal tumor that primarily affects children, often presenting as a palpable abdominal mass, hypertension, and hematuria. The disease is characterized by the abnormal proliferation of embryonic kidney cells, leading to the formation of a solid tumor.

**Why the Correct Answer is Right**
The genetic mutations associated with Wilms tumor involve the WT1 gene, which is a tumor suppressor gene that regulates cell growth and differentiation. Mutations in the WT1 gene can lead to the development of Wilms tumor. Additionally, other genes such as CTNNB1 (β-catenin), TP53, and WTX can also be mutated in Wilms tumor. These genes play critical roles in the Wnt/β-catenin signaling pathway and other cellular processes that regulate cell growth and proliferation.

**Why Each Wrong Option is Incorrect**
**Option A:** Although not directly related to Wilms tumor, mutations in the WT1 gene have been associated with Denys-Drash syndrome, a disorder characterized by Wilms tumor, nephropathy, and genital abnormalities. However, this is not the correct answer as WT1 mutations are indeed associated with Wilms tumor.
**Option B:** Mutations in the CTNNB1 gene are associated with several types of cancer, including hepatocellular carcinoma and colorectal cancer, but are not typically associated with Wilms tumor.
**Option C:** Mutations in the TP53 gene are associated with Li-Fraumeni syndrome, a disorder characterized by increased risk of several types of cancer, including sarcomas, breast cancer, and brain tumors. While TP53 mutations can be found in some cases of Wilms tumor, they are not as commonly associated with the disease as WT1 mutations.
**Option D:** Mutations in the WTX gene are associated with Wilms tumor and are considered a significant risk factor for the development of the disease. WTX mutations are often found in conjunction with WT1 mutations.

**Clinical Pearl / High-Yield Fact**
It is essential to note that the presence of a palpable abdominal mass in a child, especially in the flank region, should raise suspicion for Wilms tumor. A high index of suspicion and prompt evaluation with imaging studies, such as CT scans, are crucial for early diagnosis and treatment.

**Correct Answer: B. CTNNB1**

✓ Correct Answer: D. RAS