A Rare Case of CTNNB1-Driven Wilms Tumor Associated with Heterozygous Bloom Syndrome: Precision Oncology Insights

ABSTRACT Wilms tumor (WT), also known as nephroblastoma, is the most common pediatric renal malignancy. We present the case of a 1-year-old female child who presented with prolonged fever, cough, and gastrointestinal symptoms, later found to have a left renal mass. Imaging and histopathology confirmed a WT with diffuse anaplasia and rhabdomyoblastic differentiation. The patient was managed with neoadjuvant chemotherapy followed by radical nephrectomy with lymph node dissection. The patient progressed with metastasis to the lung highlights the significance of genetic evaluation in recurrent WT, particularly the identification of a heterozygous RECQL3/BLM (OMIM#210900) gene mutation, which may contribute to tumorigenesis and recurrence risk, and has potential implications for prognosis. Notably, genetic analysis revealed a heterozygous pathogenic variant in the BLM gene, traditionally linked to Bloom syndrome (BS), a disorder characterized by genomic instability and cancer predisposition in the homozygous condition. Despite the absence of classical clinical features of BS, such as short stature, photosensitivity, immunodeficiency, and a characteristic facial rash, this mutation may have contributed to tumorigenesis by providing a fertile environment for the development of other mutations, highlighting the potential role of monoallelic BLM variants in pediatric malignancies. This rare combination of aggressive WT histology and BLM heterozygosity emphasises the critical importance of integrating molecular diagnostics into pediatric oncology. Our findings emphasize personalized risk assessment and targeted surveillance strategies to improve outcomes in complex pediatric renal tumors.