MSH2 and Leigh syndrome: The autosomal dominant inherited tumor disposition syndrome first described by Henry Lynch in 1966 is caused by heterozygous (only one allele is affected) inactivating germline mutation in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. LS may also be due to a germline deletion of the 3′ end of the EPCAM gene, which causes epigenetic inactivation of the neighboring MSH2 gene.