TSC follows the Knudson “two-hit” tumour-suppressor gene model (Knudson, , 1971); that is, a germline alteration either occurring de novo in the zygote or inherited from an affected parent, and inactivating one allele of TSC1 or TSC2, is complemented by a second somatic alteration, often loss of heterozygosity (LOH), in the remaining wild-type allele. Here, TSC2 is linked to neoplasm.