Biallelic Mismatch Repair Deficiency in Children and Adolescents: A Review of Published and Unpublished Data from India—Need for an Indian Consortium

Introduction Biallelic mismatch repair deficiency or constitutional mismatch repair deficiency (CMMRD) is a rare and aggressive pediatric cancer predisposition syndrome that occurs as a result of homozygous (biallelic) pathogenic variants in mismatch repair genes. The primary malignancies that occur in CMMRD are mainly hematological and brain malignancies. Most published data are from the western populations and the Middle East. Data from India are limited to case reports. We performed an analysis to determine the prevalence of CMMRD in the Indian population. Materials and Methods All children aged less than 18 years with a diagnosis of CMMRD from various centers in India were included. CMMRD confirmed using genetic, molecular, and clinical criteria by an international consensus was included in the analysis. Literature search and data submitted by individual centers were reviewed. Results The analysis revealed that 22 children had genetically confirmed CMMRD. The median age of the cohort was 6.5 years, with a male predominance (male:female, 2:1). The classical phenotype of café-au-lait macules was observed in 72.7 % of subjects. The most common pathological variant was found in the PMS2 gene, which accounted for 77.3 % of children. Hematological malignancy (T cell acute lymphoblastic leukemia) was the most common primary malignancy in our study that occurred at a median age of 5 years (interquartile range 4–6 years) followed by brain tumors. The age at initial presentation for CMMRD with mutations in MSH2, MSH6, and PMS2 was 5.4, 4, and 7.5 years, respectively.