Abstracts

Rationale: Sodium channel gene (SCN1A) mutations have been described mostly in patients with generalized epilepsy especially in patients with Severe Myoclonic Epilepsy of Infancy (Dravet Syndrome) (Claes et al 2001). More recently this phenotype has been expanded and the name called Severe Myoclonic Epilepsy Borderline has been used. The current abstract describes patients with primarily localization related epilepsy with SCN1A mutations.Methods: Review of our clinical database showed seven patients with partial onset seizures and with sodium channel (SCN1A) point mutations. The patients were referred due to partial seizures and underwent video-EEG telemetry to rule-out the presence of a resectable lesion. Two patients had frequent seizures captured on an one hour Video-EEG study. DNA testing was performed by Athena Diagnostics. SCN1A analysis was done by PCR amplification of purified genomic DNA, followed by automated uni-directional DNA sequencing of the 26 exons. All abnormal sequence variants were confirmed by bi-directional sequencing or alternative sequencing chemistry. Results: All seven patients had partial seizures with variable foci demonstrated by EEG. All started having seizures during infancy. Each child had predominately or solely partial seizures. As previously demonstrated in cases of Dravet syndrome, most of these patients show increased seizures with the use of lamotrigine and carbamazepine, which also induced generalized seizures with generalized spike and wave discharges in some cases. These patients tended to respond better to certain medications with multiple mechanisms of action but always including GABAergic medications. All patients had point mutations. In 4 patients the mutations were clustered over two codons (especially 1245 and1779). The mutations were located key regions of the SCN1A protein on the pore region, voltage sensor and extracellular linkers between segments. Conclusions: SCN1A point mutations can be a cause of partial seizures with onset in infancy. Oftentimes these patients present with medically refractory epilepsy. SCN1A mutation testing should be contemplated in infants with partial seizures especially those with bilateral and independent onset. Lamotrigine or carbamazepine monotherapy should be used with caution in patients with SCN1A mutations even if they only have partial seizures. Claes et al. Am J Hum Genet 2001;68:1327-32.