Advanced Imaging Reveals Early Brain Network Disruptions in Rare Pediatric Neurological Disorder

Researchers at the VIB-UAntwerp Center for Molecular Neurology have identified early functional changes in brain connectivity associated with KCNQ2-related developmental and epileptic encephalopathy (KCNQ2-DEE), a rare neurological disorder affecting infants. Using advanced imaging techniques, the study highlights that disruptions in communication between brain regions occur well before clinical symptoms become apparent.

KCNQ2-DEE is a severe condition caused by mutations in the KCNQ2 gene, which encodes a potassium ion channel critical for normal brain function. Children affected by this disorder typically present with seizures shortly after birth, followed by persistent difficulties with cognitive and motor development. Understanding the progression of neural abnormalities in this condition is essential for the development of targeted therapies.

To investigate the disorder's impact on neurodevelopment, scientists utilized longitudinal magnetic resonance imaging (MRI) and positron emission tomography (PET) in a mouse model genetically engineered to carry the same mutation found in KCNQ2-DEE patients. Their findings, published in eBioMedicine, demonstrate that alterations in brain function, rather than structural changes, are the earliest detectable abnormalities. These functional disruptions affect the way different regions of the brain communicate and coordinate, indicating that the developmental trajectory of brain networks is altered long before behavioral or physical symptoms are visible.

The research shows that the pattern of early network dysfunction in KCNQ2-DEE resembles those observed in other neurodevelopmental disorders, such as autism spectrum conditions and schizophrenia, suggesting a broader implication of ion channel dysfunction in the maturation of neural circuits. This insight provides a new perspective on how genetic mutations affecting ion channel activity can have far-reaching effects on brain connectivity and overall development.

Importantly, the observed disruptions in brain network activity precede the onset of seizures and other outward signs of the disorder. This suggests that interventions aiming to restore normal brain function may need to be implemented at a much earlier stage than previously considered. Early identification of these changes using imaging biomarkers could improve the window for therapeutic intervention, potentially altering the course of the disease.

The team's earlier investigations also identified potential pharmaceutical agents that may target the potassium channels implicated in KCNQ2-DEE. Continued research in this area could pave the way for the development of treatments that not only address symptoms such as seizures but also target the underlying disruptions in brain network development.

These findings underscore the importance of early detection and intervention in rare pediatric neurological conditions. By using non-invasive imaging to monitor brain development over time, researchers are now better equipped to identify critical periods when therapies may be most effective. The study also highlights the value of animal models in understanding human neurodevelopmental disorders and testing potential treatments before clinical application.

Further research will be necessary to translate these findings into clinical practice and to determine whether similar patterns of early brain network disruption are present in children with KCNQ2-DEE. The insights gained from this study may also inform approaches to other childhood neurological disorders involving ion channel dysfunction.

Reference: Millevert, C. et al. Imaging brain development in a KCNQ2-developmental and epileptic encephalopathy mouse model: identifying early biomarkers for functional and structural brain changes. eBioMedicine (2025). DOI: 10.1016/j.ebiom.2025.105986