Her clinical presentation at age 27, including CALMs, a resected scalp neurofibroma, and AVM, may partially overlap with some features seen in constitutional mismatch repair deficiency syndrome (CMMRD), the biallelic form of LS; these findings are clearly insufficient to make a diagnosis of CMMRD, but this unique combination raises the possibility of a digenic interaction between genetic and epigenetic alterations in MMR genes, potentially leading to a more severe phenotype. This evidence concerns the gene MRC1 and Leigh syndrome.