In addition to the practical health services implementation issues with family history taking discussed above, this is driven by the fact that family history does not capture patients who have de novo LS mutations (aka, a new mutation not inherited from either biological parent) and because many LS patients carry MSH6 or PMS2 mutations, which confer lower overall lifetime cancer risk than MLH1 or MSH2 mutation carriers (54, 56). Here, MLH1 is linked to Leigh syndrome.