Tuberous sclerosis complex

The causal disease Tuberous sclerosis complex (TSC) is an autosomal dominant, multiorgan disease which is estimated to occur in at least 1 in 6000 live births, although the true prevalence is thought to be higher due to undiagnosed mild variants of the disease (Webb and Osborne 1995; Crino et al. 2006). It is clinically characterized by multisystem involvement and the presence of dysgenic and hamartomatous lesions in multiple organs, although expression is widely variable between individuals. The brain is frequently affected in TSC. Epilepsy is the most common symptom and often the cause of highest morbidity. Approximately half of patients with TSC are cognitively impaired and up to 40% of patients have autism or autism spectrum disorder with or without mental retardation (Webb et al. 1991; Winterkorn et al. 2007). Other frequent neurological and psychiatric manifestations include symptoms of mood disorder, anxiety, attention-deficit hyperactivity disorder, and aggressive or self-injurious behaviors (Muzykewicz et al. 2007; Staley BA 2008). Genetics and molecular physiology Approximately 85% of patients with TSC are found to have a mutation in one of two genes, TSC1 or TSC2. The TSC1 gene encodes hamartin, is located on chromosome 9p34 and, consists of a 3.4-kb coding region with 21 exons. The TSC2 gene encodes tuberin, is located on chromosome 16p13, and consists of a 5.4-kb coding region with 41 exons.