engleski

Tuberous sclerosis complex and epilepsy

Tuberous sclerosis complex (TSC) is a multi-system neurocutaneous genetic condition with autosomal dominant inheritance caused by deletion, rearrangement, and inactivating mutation of tumor suppressor genes TSC1 or TSC2. This mutation causes the overactivation of the mammalian target of rapa- mycin (mTOR) signal pathway, responsible for cellular proliferation and inhibition of cellular apoptosis. In- activation of one of the TSC genes results in hyperactivity of the mTOR pathway and the development of benign tumors or hamartomas in multiple organ systems, including skin, brain, eyes, heart, and kidneys. Clinical manifestations of TSC are protean in terms of severity and the range of tissues it can involve. Diag- nosis is based on independent clinical and genetic criteria. Epilepsy is one of the main clinical manifestations and a significant cause of morbidity and mortality in TSC. Epileptic seizures occur in 70%-90% of patients with TSC and most frequently lead to the diagnosis of the condition. Epileptic seizures usually start within the first three years of life, typically as infantile spasms and focal seizures. However, all types of epileptic seizures can occur in TSC, and two-thirds of the cases develop into refractory epilepsy. Each symptom in TSC demands evaluation and management within the relevant clinical context as a consequence of the mul- ti-system involvement. Treatment of TSC is symptomatic, although mTOR inhibitors have been ground- breaking due to their ability to target the molecular defect in the disorder.

epilepsy, mTOR inhibitors, tuberous sclerosis complex

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