The most recent National Comprehensive Cancer Network (NCCN) guidelines (Genetic/Familial High-Risk Assessment: Colorectal, Version: 1.2021; https://www.nccn.org/guidelines/category_2, accessed on 10 June 2021) for the management of familial CRC syndromes, including LS, report the cumulative cancer risk for specific DNA MMR gene mutations in LS carriers (Figure 1) [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. The gene discussed is MRC1; the disease is Leigh syndrome.