Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family

Fam Cancer. 2024 Nov;23(4):515-522. doi: 10.1007/s10689-024-00386-z. Epub 2024 Apr 30.

Abstract

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families.

Keywords: CMMRD syndrome; Colorectal cancer; High grade Glioma; Lynch syndrome; Mismatch repair gene.

Publication types

  • Case Reports

MeSH terms

  • Astrocytoma / diagnosis
  • Astrocytoma / genetics
  • Astrocytoma / therapy
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy
  • Child
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / therapy
  • DNA-Binding Proteins / genetics
  • Developing Countries
  • Exome Sequencing
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • MutS Homolog 2 Protein / genetics
  • Neoplastic Syndromes, Hereditary* / diagnosis
  • Neoplastic Syndromes, Hereditary* / genetics
  • Neoplastic Syndromes, Hereditary* / therapy
  • Pedigree*
  • Tunisia

Substances

  • G-T mismatch-binding protein
  • MutS Homolog 2 Protein
  • MSH2 protein, human
  • DNA-Binding Proteins

Supplementary concepts

  • Turcot syndrome