Tuberous sclerosis complex and epilepsy: recent developments and future challenges.
Tuberous sclerosis complex (TSC) is a congenital syndrome characterized by the widespread development of benign tumors in multiple organs, caused by mutations in one of the tumor suppressor genes, TSC1 or TSC2. About 80% of affected patients have a new mutation, and the remaining 20% have inherited a TSC gene mutation from a parent. The disorder affects approximately 1 in 6000 individuals. Cortical tubers are the neuropathological hallmark of TSC. The most common neurological manifestations of TSC are epilepsy, mental retardation, and autistic behavior. Epilepsy occurs in up to 80-90% of patients and is often intractable, with a poor response to anticonvulsant medications. While the molecular basis of TSC is well established, far less is known about the mechanisms of epilepsy in this disorder. In this article, we first summarize known clinical aspects of TSC with emphasis on its neurological features. Then, based on the molecular, pathological, immunohistochemical, neurochemical, and physiological properties of tubers in patients with TSC and in animal models, we discuss possible mechanisms of seizures and epileptogenesis in TSC. Finally, we provide an updated literature review and a consensus statement from the Tuberous Sclerosis Complex Working Group for future research into the mechanisms of epilepsy in TSC.
Holmes
Gregory L
GL
Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Hanover, New Hampshire, USA. Gregory.L.Holmes@Dartmouth.edu
Stafstrom
Carl E
CE
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D000927:Anticonvulsants / Q000627:therapeutic use; D002985:Clinical Protocols; D032921:Consensus; D004195:Disease Models, Animal; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D051381:Rats; D012107:Research Design / Q000639:trends; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology
D000927:Anticonvulsants