Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg?

Hum Genet. 2008 Sep;124(2):105-22. doi: 10.1007/s00439-008-0542-4. Epub 2008 Aug 18.

Abstract

Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause the dominant adult cancer syndrome termed Lynch syndrome or hereditary non-polyposis colorectal cancer. During the past 10 years, some 35 reports have delineated the phenotype of patients with biallelic inheritance of mutations in one of these MMR genes. The patients suffer from a condition that is characterised by the development of childhood cancers, mainly haematological malignancies and/or brain tumours, as well as early-onset colorectal cancers. Almost all patients also show signs reminiscent of neurofibromatosis type 1, mainly café au lait spots. Alluding to the underlying mechanism, this condition may be termed as "constitutional mismatch repair-deficiency (CMMR-D) syndrome". To give an overview of the current knowledge and its implications of this recessively inherited cancer syndrome we summarise here the genetic, clinical and pathological findings of the so far 78 reported patients of 46 families suffering from this syndrome.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Alleles
  • Brain Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / genetics
  • DNA Repair-Deficiency Disorders / complications
  • DNA Repair-Deficiency Disorders / etiology*
  • DNA Repair-Deficiency Disorders / genetics
  • DNA Repair-Deficiency Disorders / immunology
  • DNA-Binding Proteins / genetics
  • Genes, Neurofibromatosis 1
  • Hematologic Neoplasms / genetics
  • Humans
  • Mismatch Repair Endonuclease PMS2
  • Mutation
  • Skin Diseases / etiology
  • Skin Diseases / genetics
  • Syndrome

Substances

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