Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings

Pediatr Blood Cancer. 2020 Aug;67(8):e28309. doi: 10.1002/pbc.28309. Epub 2020 May 30.


Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.

Keywords: BMMRD; CMMRD; CNS tumors; RRD; café au lait spots; cancer genetics; hematological malignancies gastrointestinal malignancies; neurofibromatosis; surveillance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / mortality
  • DNA Mismatch Repair*
  • Genes, Neoplasm*
  • Germ-Line Mutation*
  • Humans
  • Incidence
  • Neoplasm Proteins / genetics*


  • Neoplasm Proteins