It is an autosomal dominant disorder most commonly caused by constitutional pathogenic variants in one of four mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. In approximately 1–3% of families, LS can be caused by constitutional deletions in the 3′ end of EPCAM- leading to hypermethylation and transcriptional silencing of MSH2. A small proportion of LS is caused by a de novo or inherited constitutional epimutation of MLH1 [1, 2]. This evidence concerns the gene MRC1 and Leigh syndrome.