Phenotype associated with recessively inherited mutations in DNA mismatch repair (MMR) genes

The MMR (DNA mismatch repair) system helps to maintain the integrity of the genome. This involves eliminating base–base mismatches and insertion/deletion loops, which can lead to microsatellite instability, as seen in tumour cells. Hereditary non-polyposis colon cancer is the result of dominant mutations in MMR genes, such as MLH1, MSH2 and MSH6. More recently there have been case reports of biallelic mutations in the MMR genes MLH1, MSH2 and PMS2. These result in a distinct autosomal recessive cancer predisposition syndrome. The syndrome is characterized by childhood haematological malignancies, brain tumours and the presence of café au lait patches. Second primaries occur frequently in this condition, and survival into adulthood is rare.