Currently, LS is diagnosed in patients who carry germline mutations, including point mutations or genomic rearrangements, in one of the five Mismatch Repair (MMR) genes, i.e., MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), post-meiotic segregation increased 1 (PMS1) or post-meiotic segregation increased 2 (PMS2), [6–8]. Here, MSH6 is linked to Leigh syndrome.