Cancer and constitutional Mismatch Repair Deficiency syndrome due to homozygous MSH 6 mutation in children with Café au Lait Spots and review of literature

Turk J Pediatr. 2021;63(5):893-902. doi: 10.24953/turkjped.2021.05.017.


Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations of mismatch repair (MMR) genes. CMMRD syndrome is characterised by early onset malignancies in children.

Case: Here we present affected children of consanguinous parents diagnosed with CMMRD syndrome due to germline bi-allelic MSH 6 gene mutations with café au lait spots and multiple family cancers from Turkey and reported cases with CMMRD syndrome associated MSH 6 mutation in English literature. Hence, we reviewed English literature from 1990 to 2020 using Pub-Med database. Keywords used to search included constitutional mismatch repair deficiency syndrome, childhood cancer and MSH 6 gene mutation.

Conclusions: We emphasize that the inclusion of CMMRD syndrome in the differential diagnosis of a patient who presents with cafe´ au lait spots and/or hypopigmented skin lesions and cancer especially when consanguinity and/or a history of cancer coexist in children.

Keywords: MSH 6 mutation; childhood cancer; constitutional mismatch repair deficiency syndrome.

Publication types

  • Case Reports

MeSH terms

  • Brain Neoplasms
  • Cafe-au-Lait Spots* / diagnosis
  • Cafe-au-Lait Spots* / genetics
  • Child
  • Colorectal Neoplasms
  • DNA-Binding Proteins
  • Humans
  • Mismatch Repair Endonuclease PMS2 / genetics
  • Mutation
  • Neoplastic Syndromes, Hereditary*


  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Mismatch Repair Endonuclease PMS2

Supplementary concepts

  • Turcot syndrome