Genetic epilepsies as a cause of seizures in Neonates

Abstract

The objective of this review is to summarize current knowledge on epilepsies presenting in the neonatal period and to highlight their implications for diagnosis and treatment. While most seizures in newborns are due to acute brain injuries, a significant minority are caused by genetic epilepsies, which require distinct clinical management. Advances in genetic testing have clarified the major etiologic categories, including channelopathies, synaptopathies, inborn errors of metabolism, and brain malformations. Bedside clinicians must be alert to a possible genetic epilepsy in a newborn with seizures, as precise diagnosis informs prognosis and directly guides therapy. Sodium channel blockers can improve seizure control in specific channelopathies, vitamin therapies are effective in certain metabolic epilepsies, dietary therapy is transformative in glucose transporter deficiency syndrome, and targeted approaches are emerging for tuberous sclerosis complex. Rapid exome and genome sequencing now enable timely diagnosis in critically ill neonates and support precision treatment. Even with improvements in seizure control, developmental outcomes often remain poor, underscoring the urgent need for disease-modifying therapies. In conclusion, early recognition of epilepsies in the neonatal intensive care unit is essential to optimize care today and to accelerate the development of future targeted treatments.

Keywords: Anti-Seizure Medication (ASM); EEG; Electroencephalogram; Epilepsy; Hypoxic-ischemic encephalopathy; Neonatal encephalopathy; Neonatal seizures; Neurocritical care; Seizure.