LONGITUDINAL GLOBAL AND DOMAIN-SPECIFIC NEURODEVELOPMENTAL TRAJECTORIES IN SCN1A-RELATED DISORDERS

Abstract

Pathogenic SCN1A variants are associated with a broad clinical spectrum, ranging from fever-sensitive seizure phenotypes to Dravet syndrome and developmental and epileptic encephalopathies, with highly variable neurodevelopmental outcomes. We aimed to characterize longitudinal global and domain-specific developmental trajectories in a genetically defined pediatric SCN1A cohort. This retrospective longitudinal study included seven children with pathogenic or likely pathogenic SCN1A variants who underwent two age-appropriate Griffiths developmental assessments. General Quotient (GQ), longitudinal change in GQ (ΔGQ), and all available domain-specific subquotients (SQs) were analyzed using version-specific interpretation. The cohort comprised four girls and three boys, with a median age at seizure onset of 10 months (range, 0–48). Fever sensitivity was present in all seven children; six had a history of status epilepticus, and four had drug-resistant epilepsy. Median GQ was 84 (range, 42–100) at the first assessment and 80 (range, 38–98) at follow-up, with marked interindividual variability in longitudinal change (ΔGQ, −21 to +9). Across 14 assessments, 73 domain-specific SQs were available. In the five assessments with globally preserved development, 25 of 26 SQs (96.2%) were within the expected or average range, with no recurrent domain-specific deficit. In contrast, assessments with lower global scores showed predominantly heterogeneous multidomain involvement. These findings highlight marked heterogeneity in longitudinal neurodevelopment across the SCN1A spectrum and support serial assessment of both global and domain-specific development to capture clinically meaningful change over time.