Related Experiment Video
Updated: Dec 26, 2025
Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization
Published on: September 20, 2024
KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases
Felippe Borlot1, Ahmed Abushama1, Nadine Morrison-Levy1,2
1Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
This study highlights KCNT1-related epilepsy, often presenting as epilepsy of infancy with migrating focal seizures (EIMFS) and refractory tonic seizures. Cannabidiol, diet, and quinidine show promise for seizure reduction in these patients.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- KCNT1 gene variants are associated with severe early-onset epilepsy syndromes.
- Understanding genotype-phenotype correlations is crucial for managing KCNT1-related epilepsy.
- A multiethnic cohort evaluation provides insights into phenotypic variability.
Purpose of the Study:
- To evaluate phenotypic aspects of KCNT1-related epilepsy in a multiethnic cohort.
- To explore genotype-phenotype correlations for common KCNT1 variants.
- To identify potential therapeutic strategies for seizure control.
Main Methods:
- Cross-sectional analysis of children with pathogenic/likely pathogenic KCNT1 variants.
- Comparison of children with common recurrent variants versus the rest of the cohort.
- Phenotypic data collection including seizure types, developmental trajectory, and treatment response.
Main Results:
- Twenty-seven children were included, with seizure onset typically in early infancy.
- Epilepsy of infancy with migrating focal seizures (EIMFS) and focal tonic seizures were prevalent.
- Cannabidiol, diet therapy, and quinidine demonstrated potential for seizure reduction, though evidence is limited.
Conclusions:
- KCNT1-related epilepsy is a highly pleiotropic condition with common features like EIMFS and refractory tonic seizures.
- Cannabidiol, diet therapies, and quinidine represent promising avenues for seizure management.
- Further evidence-based research is needed to establish optimal treatment protocols.
Objective:
Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants.
Methods:
A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.
Results:
Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.
Significance:
Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.
More Related Videos
10:22Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy
Published on: December 6, 2016
11:54Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy
Published on: January 29, 2018
Related Concept Videos
01:13Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types:
01:24Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...