Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 ( TSC1 ) and 16p13 ( TSC2 ). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1 , 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.

Epilepsy appears in 70-80% of patients with tuberous sclerosis complex, most commonly in the first year of age. Early manifestation of epilepsy is associated with drug-resistant epilepsy and mental retardation in more than 80% of patients. Clinical epileptic seizures are preceded by deterioration of EEG recording thus infants with high risk of epilepsy can be identified. We hypothesized that preventative antiepileptic treatment of infants with multifocal activity on EEG might lower the incidence of drug-resistant epilepsy and mental retardation. Forty-five infants with early diagnosis of tuberous sclerosis complex were included in the open-label study. They were divided in two groups: standard (n=31) and preventative one (n=14). In standard group the antiepileptic treatment was launched early, but after the onset of seizures. In preventative group medication was commenced when active epileptic discharges were seen on EEG, but before the onset of clinical seizures. Children were followed till the end of 2 years of age. At 24 months of age mental retardation was significantly more frequent and severe in "standard" vs "preventative" group (48% vs 14%; p=0.031; mean IQ score 68.7 vs 92.3; p<0.05). The "preventative" group was characterized by higher ratio of seizure-free patients (93% vs 35%; p=0.004), lower incidence of drug-resistant epilepsy (7% vs 42%; p=0.021) and lower number of patients requiring polytherapy (21% vs 55%; 0.039) than the "standard group. Preventative antiepileptic treatment of infants with tuberous sclerosis complex and high risk of epilepsy markedly improves their neurodevelopmental outcome and reduces the incidence of drug-resistant seizures.