Clinical severity is correlated with age at seizure onset and biophysical properties of recurrent gain of function variants associated with SCN8A-related epilepsy.

This is one of the first studies to identify statistically significant G-P correlations for individual SCN8A variants with GOF properties. The results suggest that individual GOF variants 1) are predictive of clinical severity for individuals carrying those variants, and 2) may underlie distinct clinical phenotypes of SCN8A disease, thus helping to explain the wide SCN8A-related epilepsy disease spectrum. These results also suggest that certain features present at initial diagnosis are predictive of clinical severity, and with more informed treatment plans, may serve to improve prognosis for patients with SCN8A GOF variants.