LS is caused by pathogenic/likely-pathogenic variants in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2 [28], by 3′ deletion of the EPCAM gene, which causes the epigenetic silencing of MSH2, or by the methylation of the MLH1 promoter [3,14,15,16,29,30]. Here, PMS2 is linked to Leigh syndrome.