Abstracts

Rationale: Mutations in the voltage gated sodium channel genes SCN1A, SCN2A, SCN3A and SCN8A have been linked to infantile and childhood epilepsy syndromes. At least 48 different SCN2A mutations have been described in various syndromes, including benign familial neonatal infantile seizures, GEFS+, Ohtahara syndrome, infantile spasms, Dravet syndrome, Lennox Gastaut syndrome, and other unclassified intractable epilepsies. Methods: We have identified novel mutations in SCN2A in three patients with medically refractory epilepsies, through the use of epilepsy gene panel sequencing. Results: Patient #1 (1027G>C/p.D343H) developed seizures at day 1 of life and was diagnosed with Ohtahara syndrome. Seizures were refractory to multiple medications as well as ketogenic diet and the patient died at 15 months of age with hospice support. Patient #2 (2713A>G/p.K905E) developed seizures at 3 weeks of life and was diagnosed with malignant migrating partial epilepsy in infancy (MMPEI). Seizures were medically refractory and the patient, currently 21 months old, remains on three anti-seizure medications. Patient #3 (4609A>T/p.I1537F) developed seizures in the first week of life and was diagnosed with infantile epileptic encephalopathy; severe dystonia developed at 8 months of age. Seizures were initially medically refractory in this patient, now 20 months old, but are now well controlled on 2 anti-seizure medications; dystonia was initially severe and refractory to many medications but has gradually improved. Conclusions: These cases demonstrate the difficulties of correlating SCN2A mutational genotype with seizure syndrome phenotype. It is also important to recognize that mutations in SCN2A may not only cause epilepsy, but can be associated with refractory dystonia. Future work into functional analysis of SCN2A mutations may help elucidate the role of this sodium channel in childhood epilepsy and lead to targeted treatments. Funding: None