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CC BY 4.0 · Indian J Med Paediatr Oncol
DOI: 10.1055/s-0044-1790202
Original Article

Biallelic Mismatch Repair Deficiency in Children and Adolescents: A Review of Published and Unpublished Data from India—Need for an Indian Consortium

Gazel Sainulabdin 
1   Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India
,
Purva Kanvinde
2   Department of Pediatric Hematology Oncology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
,
Ritika Khurana 
2   Department of Pediatric Hematology Oncology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
,
Sangeeta Mudaliar
2   Department of Pediatric Hematology Oncology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
,
Vasudeva Bhat K
3   Department of Pediatric Hematology Oncology, Kasturba Medical College, Manipal, Karnataka, India
,
Anju Shukla
4   Department of Medical Genetics, Kasturba Medical College, Manipal, Karnataka, India
,
V. P. Krishnan
1   Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India
,
Yamini Krishnan 
1   Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, MVR Cancer Centre and Research Institute, Kozhikode, Kerala, India
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Abstract

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.

Conclusion The diagnosis of CMMRD requires a high index of suspicion for the early diagnosis, management, surveillance, counseling, and testing of family members. The awareness about CMMRD in clinicians is important so that diagnosis is made early, and a second malignancy is detected and treated early. The need for an Indian consortium to determine the actual burden of the disease, genetic characteristics, and course of illness in our country has been emphasized.

Keywords

CMMRD - India - childhood and adolescence - genetic testing

Patient Consent

The written consent of caregivers for publication has been obtained.


Ethical Issues

None.


Institutional Ethics Committee Approval Obtained

IEC2023/III/2.


Supplementary Material



Publication History

Article published online:
27 September 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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