Tuberous Sclerosis and Autism

Tuberous sclerosis (TSC) is a single-gene disorder caused by heterozygous mutations in either the TSC1 or TSC2 genes (Consortium, 1993; van Slegtenhorst et al., 1997). In 70% of cases, TSC gene mutations arise de novo. The remaining 30% of cases are familial with an autosomal dominant pattern of inheritance. Tuberous sclerosis belongs to the group of phakomatoses (neurocutaneous disorders) and is associated with characteristic manifestations in various organ systems, including the brain, skin, kidney, lung, heart, and liver (Crino, Nathanson, & Henske, 2006; Curatolo, Bombardieri & Jozwiak, 2008). Pathological manifestations in these organ systems often include tumor growths or tissue malformations (hamartomas). While penetrance is high, expressivity of TSC phenotypes is highly variable. The birth incidence of TSC is approximately 1:6,000 (Osborne, Fryer, & Webb, 1991). This chapter is an updated and extended version of a previous article on this topic (Ehninger, de Vries, & Silva, 2009)