MLH1 and Leigh syndrome: [2–4] This autosomal dominant condition is caused by pathogenic variants in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) [5, 6] and deletions in EPCAM which result in inactivation of MSH2. [7, 8] Despite a prevalence estimate of 1 in 279 for LS in the United States general population, less than 2% of people affected by LS have been diagnosed.