Complex Neurocognitive Skills Delayed in Youth With SCN8A Variant Epilepsy

genetic code
genetic code
In the first study of this size, researchers found complex neurocognitive skills, typically acquired later in development, are the most delayed skills in youth with SCN8A‐related epilepsy.

Complex neurocognitive skills, typically acquired later in development, are the most delayed skills in youth with SCN8A‐related epilepsy, according to results published in Epilepsia.

Researchers analyzed 91 patients with SCN8A-related epilepsy. Analyses were conducted to identify correlations between age at seizure onset and neurodevelopmental growth. Parents and guardians provided information pertaining to their child’s medications, seizure history, comorbidities, and developmental skills based on Denver II items. Twenty-five skills were chosen, six to seven from each category (fine motor, gross motor, social motor, and language).

Researchers carried out a retrospective analysis of data from an online SCN8A community registry and used the canonical transcript to map all genetic variants collected. Spearman rank tests were used to evaluate pairwise relationships between certain seizure characteristic variables and development score.

Results from the 91 patients revealed 71 missense variants, 41 of which were newly reported. Additionally, of these 71 missense variants, 9 were recurrent with 1 variant present in 4 cases. Three truncating variants were also identified: 1 frameshift, 1 nonsense, and 1 splice site variant.

Less than 5% of patients (n=4) never presented with a seizure. Age of seizure onset ranged from birth to 50 months (mean±SD=5 months 21 days±7 months 14 days).

From the cohort of 91 children, 71 parents (78%) reported their child did not experience age‐appropriate neurodevelopment. A positive correlation was identified between developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. A clear distinction was observed between children with a single reported variant in SCN8A vs children with an additional variant (in a gene other than SCN8A). Researchers report that a developmental delay or regression that occurs before and/or at seizure onset impacts the pattern of skill acquisition.

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A limitations of this study included the potential for recall error in questionnaires completed by parents and guardians. Further, cohort included was not large enough to produce statistically significant tests and prevented further stratification based on subphenotypes or mutational type.

Researchers concluded that variants of uncertain significance should be taken into consideration when evaluating children with SCN8A-related epilepsy. Researchers believe these findings provide “a clinical context at initial presentation that may be prognostic for developmental outcome.”

Disclosure: This clinical trial was supported by Xenon Pharmaceuticals, Inc. Please see the original reference for a full list of authors’ disclosures.

Encinas AC, Moore IKM, Watkins JC, Hammer MF. Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohortEpilepsia. 2019;60(8):1711–