Abstracts

Rationale: Early life genetic epilepsies are a group of complex diseases characterized by seizures, comorbid developmental delays or regression, as well as movement difficulties. With this study, we sought to characterize the phenotype of two rare early life epilepsies: SLC13A5 and GNAO1 mutation with prominent epilepsy and movement disorders. The rarity of these disorders pushed us to use a remote clinical metric to characterize the adaptive behaviors (achievement of social, motor, and functional milestones). We aimed to establish a metric for future outcomes study beyond seizure count. Methods: Families of children with SLC13A5 and GNAO1 mutation were identified through the respective family foundations (TESS and Bow). Electronic informed consent was obtained and families completed an electronic questionnaire in a secure database with questions regarding antiepileptic drugs (AEDs), seizure types, movement disorder medications, and movement disorder severity. These were repeated if multiple children in the family were affected. Upon completion, families received a link to the Vineland Adaptive Behavior Scale-III (VABS) Comprehensive Parent/Caregiver form for remote on-screen administration. Results: 22 patients from 16 families with SLC13A5 mutation enrolled. The mean age was 8.4 years (3 months-23 years). All except one began having seizures in the first week of life. 17 reported tonic clonic seizures, 4 myoclonic, 3 absence, 3 motor only, and 1 infantile spasms.  Patients had been on a large number of AEDs; phenobarbital (4) and valproic acid (3) were most frequently noted as most efficacious. Half were currently having seizures less than once a month, and 3 were reported to be seizure free for over a year, but only one was currently weaned off AEDs. 11 reported movement disorder but only 2 were currently on medications (valproic acid and gabapentin), specifically for treatment of the movement concerns. 16 patients (discrete families) with GNAO1 mutation enrolled. The mean age was 3.8 years (15 months-12 years). Six reported never having seizures. Six reported seizures starting in the first week of life, and 4 before one year of age. 2 patients are currently in remission on AEDs. There was no trend in current or most effective AEDs, though 7 are on the ketogenic diet. Thirteen reported movement disorder, with tetrabenazine (2) and clonazepam (2) the most efficacious medications. Seven patients with SLC13A5 and 5 patients with GNAO1 mutation have completed the VABS to date. The social domain was a strength for both cohorts with mean domain score 73 and 69, respectively (standardized mean score 100). The motor domain was a weakness for both with mean domain score 55 and 41, respectively. The subdomain of gross motor was a further weakness for both with mean V-scale score (standardized mean score 15) of 4.2 and 2, respectively. Conclusions: A relatively large cohort of patients for rare epilepsy syndromes can be characterized using remote online questionnaires. The enrollment can be facilitated by parent organizations for identification and encouragement of families from around the world to participate. Our data indicate that distinct genotype-phenotypes could be identified. Patients with SLC13A5 always commence with seizures as neonates and not all have identified movement disorders. Patients with GNAO1 in contrast have less epilepsy but the movement disorder is more severe. Funding: The TESS Research Foundation provided funding for this study.