On the other hand, population-based epidemiological studies have recently shown that, not only LS is less rare and less penetrant than previously thought, but that PMS2 and MSH6 pathogenic variants are the most prevalent, thus suggesting a lower cancer risk for PMS2 and MSH6 pathogenic variants compared to MLH1 and MSH2 (Win et al., 2017). This evidence concerns the gene MSH6 and Leigh syndrome.