Considering the above discussion, it cannot be excluded that the clinical phenotypic variability in TSC, including tumor development, progression, and neurological problems, is partly due to the second hit in epigenetic modification of VDR and vit D-metabolizing enzyme genes by the environment, as well as dietary and supplemental vitamin D intake, use of multiple anticonvulsants, and reduced sun exposure. This evidence concerns the gene VDR and tuberous sclerosis.