Abstracts

Rationale: Mutations of the DEPDC-5 (DEP domain containing protein 5) gene account for 12 to 37 % of inherited focal epilepsies. DEPDC-5 is an upstream negative regulator of rapamycin (mTOR) complex 1. The mTOR signaling pathway regulates many major cellular processes, and its up-regulation is causally linked to epileptogenesis. Recently an association with familial focal epilepsy and focal cortical dysplasia (FCD) has been described and so far only seven families with this mutation were published. Notably, 11/13 affected subjects had FCD in the frontal lobe (Scheffer, Ann Neurol 2014;75:782; Baulac, Ann Neurol 2015;77:675; Scerri, Ann Clin Transl Neurol 2015;2:575). We report on five subjects from three new pedigrees combining focal epilepsy and FCD.Methods: We reviewed patients’ history including family antecedents, seizure semiology, EEG, and neuroimaging findings.Results: Three of the 5 patients had drug-resistant focal epilepsy (Table 1). In four patients, semiology was indicative of frontal lobe seizures (mostly or exclusively brief nocturnal attacks with vocalization, hypermotor behavior, and immediate recovery), with scalp EEG spiking activity in the frontal regions. The three drug-resistant patients showed MRI abnormalities in the anterior and mesial frontal lobe consistent with FCD type II, which was histologically proven in one of the patients who underwent surgery (Figure 1). The remaining two patients are well controlled on carbamazepine; scalp EEG was normal in one patient and showed right temporal spikes in the other. Genetic testing revealed mutations in the DEPDC-5 gene in one family, and results are pending in the remaining two pedigrees.Conclusions: DEPDC-5 gene mutations provide communality for pedigrees combining focal epilepsy associated with FCD. Notably, in the vast majority of all reported cases so far the FCD was located in the frontal lobe. Albeit with a more benign phenotype, these pedigrees present some analogies with families with tuberous sclerosis complex.