Neuropsychological profiles of two patients with differing SCN8A-pathogenic variants
Related Experiment Video
Updated: Dec 10, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
L Collins Medlin1, Luis Bello-Espinosa1,2,3, William S MacAllister1,2,3
1Alberta Children's Hospital, Calgary, Canada.
Insights
SCN8A-related epilepsy presents diverse cognitive and neuropsychological impacts in children. Unique genetic variants influence the severity of intellectual disability and developmental delays, underscoring the need for individualized care.
Area of Science:
- Neurogenetics
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Gene-related epilepsies in early infancy can severely impact cognitive development.
- SCN8A-related epilepsy is a significant cause of early-onset epileptic encephalopathy.
- Understanding the neuropsychological heterogeneity associated with SCN8A variants is crucial for patient management.
Observation:
- Two cases of SCN8A-related epilepsy with distinct de novo pathogenic variants are presented.
- Case 1: SCN8A-developmental and epileptic encephalopathy (SCN8A-DEE) with a novel missense variant, presenting with mild intellectual disability and widespread neuropsychological deficits.
- Case 2: SCN8A-related epilepsy with a different pathogenic variant, showing preserved intellect but attention deficits, motor delays, and behavioral comorbidities.
Findings:
- SCN8A-DEE is strongly associated with intellectual disability and significant neuropsychological impairments.
- Distinct SCN8A pathogenic variants can lead to varied cognitive profiles, ranging from severe ID to preserved intellect with specific deficits.
- Neuropsychological heterogeneity includes delays in speech, motor skills, attention, executive functions, and behavioral issues like tics and ADHD.
Implications:
- These cases expand the understanding of the neuropsychological spectrum in SCN8A-related epilepsies.
- The findings highlight that not all SCN8A pathogenic variants result in severe intellectual disability, emphasizing the importance of genetic variant-specific assessment.
- Tailored therapeutic and educational strategies are essential to address the diverse neuropsychological and behavioral needs of affected children.
Abstract:
The impact of gene-related early infancy onset epilepsies in cognitive development can be potentially devastating. Here we report two cases of SCN8A-related epilepsy that highlight the neuropsychological heterogeneity seen with differing de-novo pathogenic variants. Case 1 is a 6-year-old right-handed girl who presented with SCN8A-developmental and epileptic encephalopathy (SCN8A-DEE) and a missense pathogenic variant (c.802A > C), not previously documented in the literature. Her history includes speech and motor delay, with focal motor seizures starting at 4-months. Early EEG showed bilateral centroparietal epileptiform discharges. She shows motor and language delays and prominent motor tics. Testing documented Intellectual Disability (ID) (Mild) with widespread neuropsychological deficits (i.e., academics, attention/executive functions, memory, visual-spatial skills, fine motor, language). Case 2 is an 8-year-old right-handed girl who presented with SCN8A-related epilepsy with c.5630A > G pathogenic variant with seizure onset at 5-months. Her initial EEG showed right occipital spikes. She shows low average intellect and average academics, but evaluation documented attention deficits, fine motor delays, and behavioral issues in addition to tics; she was diagnosed with Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Obsessive Compulsive Disorder, and Tourette's. These cases expand limited knowledge regarding neuropsychological functioning of children with SCN8A-related epilepsy with unique de-novo pathogenic variants. While SCN8A-DEE is clearly associated with ID, other pathogenic variants may show better preserved intellect, despite other neuropsychological and behavioral concerns.
