Figure 3.

Haploinsufficiency‐ and two‐hit‐initiated pathologies in tuberous sclerosis complex (TSC). Germline mutations (1st hit) cause neuropsychiatric symptoms during infancy without a 2nd hit. Other lesions, such as cortical tubers in brain may be caused by haploinsufficiceny of TSC genes. The majority of tumorous lesions develop after two hits of TSC genes. In animal models, tumorigenesis without a 2nd hit has been reported. Although not depicted in this figure, there are interactions between two‐hit‐initiated tumorous cells and surrounding non‐tumorous cells to form lesions.