Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin

Clin Genet. 2011 Oct;80(4):394-7. doi: 10.1111/j.1399-0004.2010.01543.x. Epub 2010 Oct 6.


Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli / diagnosis*
  • Adenomatous Polyposis Coli / genetics
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Genomic Instability
  • Genotype
  • Humans
  • Microsatellite Repeats
  • Mutation
  • Neoplastic Syndromes, Hereditary / diagnosis*
  • Neoplastic Syndromes, Hereditary / genetics
  • Pedigree
  • Skin / pathology
  • Young Adult


  • DNA-Binding Proteins
  • G-T mismatch-binding protein

Supplementary concepts

  • Turcot syndrome