J Invest Dermatol 2016 01;136(1):15-23
Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:
A number of critical signaling pathways are required for homeostatic regulation of cell survival, differentiation, and proliferation during organogenesis. One of them is the PI3K-AKT-mTOR pathway consisting of a cascade of inhibitor/activator molecules. Recently, a number of heritable diseases with skin involvement, manifesting particularly with tissue overgrowth, have been shown to result from mutations in the genes in the PI3K-AKT-mTOR and interacting intracellular pathways. Many of these conditions represent an overlapping spectrum of phenotypic manifestations forming a basis for novel, unifying classiﬁcations. Identiﬁcation of the mutant genes and speciﬁc mutations in these patients has implications for diagnostics and genetic counseling and provides a rational basis for the development of novel treatment modalities for this currently intractable group of disorders.