Constitutional mismatch repair deficiency syndrome: Clues from the clinic, proof in the genes

Constitutional mismatch repair deficiency (CMMRD), a rare autosomal recessive cancer predisposition syndrome, is characterized by neurocutaneous stigmata and early-onset aggressive multisystem malignancies. Data from low and middle-income countries is limited. Eight children, 6 boys and 2 girls, with genetically confirmed CMMRD from 2014-2025 were analysed. The median age at first malignancy was 7 years (range: 1-13). Consanguinity was noted in 62% and family history of malignancy was present in 75%. T-lymphoblastic lymphoma was the most common first malignancy (50%; n=4). Mutations in MSH6 (n=3), PMS2 (n=3), MSH2 (n=1) and MLH1 (n=1) genes were identified. Café au lait macules (CALMs) were present in 88%. Anomalies were observed in all 4 patients who underwent MRI Brain. Six were alive at last follow-up. Family history, consanguinity and CALMs, provide vital clues toward underlying CMMRD. Early diagnosis helps in planning surveillance, early identification of subsequent malignancies and family screening.