Our objective is to present two cases of patients with SCN9A mutations and medically refractory epilepsy, highlighting a potential association between SCN9A and epilepsy. 

Mutations in voltage-gated sodium channels are known to contribute to epilepsy syndromes. While SCN8A gene mutations have been better described in epilepsy phenotypes, less is known about SCN9A. Recent studies refute a gene disease association between SN9A and epilepsy, but these two cases suggest otherwise.  

Patient A is a 5-year-old male with seizure onset at age 2 years with focal, myoclonic, and tonic seizures. His seizures were refractory to brivaracetam, lacosamide, zonisamide, oxcarbazepine. He is currently on clobazam, felbamate and valproic acid, with seizures occurring every other week. Genetic testing revealed a heterozygous pathogenic SCN9A mutation c.1642C>T (p.Arg548*), resulting in a premature stop codon causing truncated NaV1.7 protein. This loss-of-function mutation has not been previously described in literature for epilepsy phenotype. Patient B is a 15-year-old male with seizure onset at age 6 years with myoclonic and generalized tonic-clonic seizures. His seizures were refractory to lamotrigine, felbamate, divalproex sodium, and oxcarbazepine. VNS placement did not improve seizure control. He is currently on zonisamide, levetiracetam, rufinamide, cannabidiol, and clobazam and continues to have seizures every few days. Genetic testing revealed an SCN9A mutation c.2318C>G (p.Thr773Ser) and a GUF1 gene mutation c.662G>C (p.C221S). The specific SCN9A mutation was initially classified as a variant of unknown significance however later addended as likely benign.

These cases demonstrate SCN9A gene mutations in patients with refractory epilepsy, suggesting a possible link. These specific gene mutations have not been well characterized in literature; thus, these cases may provide insight into mutations that may be pathogenic. Further research is necessary to determine exactly what role these variants play in epilepsy.