Researchers have discovered a “missing mutation” in severe infant epilepsy — long-suspected genetic changes that might trigger overactive, brain-damaging electrical signaling leading to seizures. They also found early indications that specific anti-seizure medications might prevent disabling brain injury by controlling epilepsy during a crucial period shortly after birth.
“These are still early days, but we may be able to use this knowledge to protect the newborn brain and improve a child’s long-term outcome,” said study leader Ethan M. Goldberg, MD, PhD, a pediatric neurologist at Children’s Hospital of Philadelphia.
Goldberg collaborated with European and American researchers in this neurogenetic study of early infantile epileptic encephalopathy, published online Feb. 21, 2018 in Annals of Neurology.
The study focused on mutations in the gene SCN3A. Scientists already knew that the gene had a pattern of high expression in the brain, before and shortly after birth. Variants in SCN3A had also been previously linked to less severe forms of epilepsy, but the current research solidified this link and was the first to establish that SCN3A mutations cause the severe infantile form.
Translating these findings into potential clinical treatments, Goldberg stressed, will require considerable further research — both in nerve cells and in future animal models, in which neurologists can test possible precision-medicine treatments for safety and efficacy before they can be investigated in patients. In addition, the current research allowed the SCN3A gene to be added to an existing diagnostic test, CHOP’s Epilepsy Panel, which uses next-generation sequencing to rapidly test for over 100 genetic causes of childhood epilepsy.
Precise, early diagnosis, added Goldberg, will be crucial, because of the highly regulated timetable of early-life neurological events. “The mutation’s activity in the Nav1.3 sodium ion channel occurs during a short period in newborns, but if we can intervene during that window, we may be able to help prevent long-term neurological injury and benefit patients,” he said.