Abstracts

Rationale: Epilepsy is present in 80% of patients with Tuberous Sclerosis Complex (TSC). The most represented seizure types are infantile spasms and focal seizures. The aim of this study was to characterize the epileptological phenotype of individuals with a clinical diagnosis of TSC but no mutation identified (NMI) in the known causative genes with current molecular methods, and to compare it to the phenotype of TSC1 and TSC2 patients.Methods: Clinical and genetic features of 238 patients with a definite clinical diagnosis of TSC followed at the TSC Clinic of the San Paolo Hospital in Milan have been recorded in an ad hoc database. Among all the patients, 22 NMI individuals were selected. Their electroclinical characteristics were evaluated and compared with those of the TSC1 and TSC2 patients. Statistical analyses were performed using the Stata13 software.Results: Twenty-two patients had no mutation in TSC1 or TSC2 after testing for point mutations and deletions/duplications. Median age at the last follow-up was 26.5 years (range 2-57). Epilepsy was present in 12 NMI patients (54.55%); all of them had focal seizures. Two other individuals presented with a single seizure. Median age at epilepsy onset was 5 years (range 3 months-27 years). Of the 12 patients with epilepsy, only two (16.67%) showed infantile spasms; no one ever experienced febrile seizures or status epilepticus. In 7 patients (58.33%) seizures were no longer present at the last follow up. Data on drug resistance were available for 10 patients: seven of them showed drug resistant seizures. By comparing TSC2 and NMI patients, we found that epilepsy was significantly less frequent in NMI individuals (p=0.010), as well as infantile spasms (p=0.012). Median age at seizure onset was higher (p=0.001), and 46.15% vs 86.79% of the patients had epilepsy onset before age 3 years (p=0.002). We didn’t find statistically significant differences between the two groups with respect to drug resistance. By comparing TSC1 and NMI patients, we couldn’t find any statistically significant differences with respect to epilepsy.Conclusions: Epilepsy was present in about half of the TSC patients with no mutation identified. Focal seizures, with onset often later in life, were the most represented type of seizures, while infantile spasms occurred very rarely. Overall, the epileptological phenotype of the NMI patients was milder than the one of the TSC2 patients, but did not differ from the one of the TSC1 patients.