Article published by Brain
A new Northwestern Medicine study helps explain how changes in the SCN2A gene affect whether a child will develop autism or epilepsy, the age at which seizures start for those with epilepsy, and the severity of the child’s other impairments. The study represents a collaboration between an academic laboratory at Northwestern and the FamilieSCN2A Foundation, a parent-led rare disease advocacy group. The SCN2A Clinical Trials Readiness Study (SCN2A-CTRS) recruited 81 families from around the world and collected detailed clinical data and information to identify their SCN2A variants. The Northwestern team extensively analyzed the functional effects of each SCN2A variant on sodium channels—tiny gates in the membranes of nerve cells that control the flow of sodium ions into the cell and help neurons in the brain fire properly. Variants in the SCN2A gene alter how the sodium channel functions. Depending on the individual variant, the channel may be hyperactive or completely inactive. The study found that the clinical condition of the child varied with the functional impact on the channel. Hyperactive channels were generally associated with seizure onset in the first week of life. More impaired channel function was more common when the age of seizure onset was older. In fact, almost all of those without seizures had completely inactive sodium channels. As age at seizures-onset increased and channels became less active, severe neurological impairments in the child tended to be less severe. “Our new study clarifies the relationship between the functional consequences of SCN2A mutations, the primary phenotype (autism versus epilepsy and age at seizure onset in those with epilepsy), and the overall severity of the child’s impairments (mobility, etc.),” said co-corresponding author Dr. Alfred George, chair of pharmacology at Northwestern University Feinberg School of Medicine. Dr. Anne Berg, adjunct professor of neurology at Feinberg, lead investigator of the SCN2A-CTRS and the co-corresponding study author, emphasized that “this collaboration between a family foundation and a large NIH-funded project is an exemplar of the new partnerships that are needed and increasingly being developed to provide rapid answers to critical questions and lay foundation for successful drug development for severe neurodevelopmental disorders such as those associated with SCN2A.”