Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2

Pediatr Blood Cancer. 2008 Jun;50(6):1268-70. doi: 10.1002/pbc.21514.


A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adolescent
  • Alleles
  • Cafe-au-Lait Spots / complications
  • Cafe-au-Lait Spots / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / genetics*
  • DNA-Binding Proteins / genetics*
  • Germ-Line Mutation*
  • Humans
  • Male
  • Mismatch Repair Endonuclease PMS2
  • Mutation, Missense*
  • Pedigree


  • DNA-Binding Proteins
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • DNA Repair Enzymes