Tuberous Sclerosis Complex

SUMMARY TSC is a commonly recognized autosomal-dominant neurocutaneous disorder thatexemplifies both genetic heterogeneity and phenotypic variability. The underlyingpathophysiology of TSC involves critical intracellular signaling cascades that regulatemany cellular functions, including intermediary metabolism, cell growth, and prolifer-ation. TSC serves as a model for other neurodevelopmental and neurodegenerativeconditions, which result from parallel and overlapping molecular mechanisms. Thetherapeutic targeting of mTORC1 has been demonstrated to reverse some of the clin-ical phenotype of TSC and heralds the possibility of even more effective interventionsin the future. REFERENCES 1. Gomez M, Sampson J, Whittemore V, editors. The tuberous sclerosis complex.Oxford (UK): Oxford University Press; 1999.2. Hyman MH, Whittemore VH. National Institutes of Health consensus conference:tuberous sclerosis complex. Arch Neurol 2000;57:662–5.3. European Chromosome 16 Tuberous Sclerosis Consortium. Identification andcharacterization of the tuberous sclerosis gene on chromosome 16. Cell 1993;75:1305–15.4. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberoussclerosis gene TSC1 on chromosome 9q34. Science 1997;277:805–8.5. Dabora SL, Joswiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tu-berous sclerosis patients indicates increased severity of TSC2, compared toTSC1, disease in multiple organs. Am J Hum Genet 2001;68:64–80.6. Cheadle J, Reeve M, Samson J, et al. Molecular genetic advances in tuberoussclerosis. Hum Genet 2000;62:345–57.7. Au KS, Williams AT, Roach ES, et al. Genotype/phenotype correlation in 325 indi-viduals referred for a diagnosis of tuberous sclerosis complex in the UnitedStates. Genet Med 2007;9:88–100.8. Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and -2 geneproducts function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A 2002;99:13571–6.