Abstracts

Rationale: Severe early life epilepsies have been associated with pathogenic variants in the SCN2A gene, which codes for the voltage-gated sodium channel, Nav1.2. There is a wide range of clinical severity, including diverse seizure semiology, differing degrees of developmental delay, and varied comorbidity burden. Infantile spasms (IS) is one of the several seizure types experienced by children with SCN2A-related epilepsy. IS, however, represents a distinct epileptic encephalopathy with its own unique prognosis and treatment plan. This study aims to determine how the presence of IS, either as initial or subsequent seizure type, correlates with phenotype and response to treatment. in infants with SCN2A-related epilepsy. Methods: Children with pathogenic SCN2A variants were recruited into a study of epileptic channelopathies.  Parents reported information regarding seizure onset, genetic variants, medications used for seizures and response to those medications. Results: Of 33 children (11 female, 22 male) with SCN2A pathogenic variants, 55% (N=18) reported having infantile spasms, 24% (N=8) reported not having infantile spasms, and 21% (N=7) did not respond to the specific survey question. Nonresponders were omitted.  Comparisons of reported seizure types by history of infantile spasms (N=18) versus no history of infantile spasms (N=8) found that similar seizure types were reported in both groups, but myoclonic and tonic seizures were more commonly reported in infantile spasms patients (Figure 1).  Patients with a history of IS had higher rates of all specific comorbidities surveyed except autistic spectrum disorder (Figure 2). Four subjects did not receive a trial of the FDA-approved treatments for IS, specifically ACTH or vigabatrin. Of the remaining 14 children, 7 received both, 2 received ACTH only, and 5 received vigabatrin only. One third reported improvement with ACTH and 42% with vigabatrin (p-value=0.5279). Conclusions: IS a major seizure type associated with SCN2A-related epilepsy in this cohort. Children who develop IS may have different seizure types in the future, namely tonic seizures, which may inform selection of anticonvulsant treatments. In this limited sample, the positive response to the FDA-approved treatments for IS appears lower than is generally reported in larger etiologic non-specific studies. This highlights the need for additional genotype and functional analysis of this subgroup of SCN2A-related epilepsy and developmental of more effective targeted treatments. Funding: None