KCNJ11 ‐associated infantile epileptic spasms syndrome and neonatal diabetes

Abstract

Objective: To report the case of an infant with infantile epileptic spasms syndrome (IESS) and neonatal diabetes associated with a pathogenic variant in the KCNJ11 gene. Methods: We evaluated the electroclinical and ketoacidosis findings, molecular features, and response to treatment. Genetic testing was performed using next-generation sequencing panels targeting epilepsy and neonatal diabetes-related genes.Results: The patient was a 2-month-old girl who presented with epileptic spasms, hypsarrhythmia on EEG, delayed developmental milestones, and poorly controlled diabetes despite insulin therapy. A heterozygous pathogenic variant in the KCNJ11 gene was identified. This variant has been previously associated with DEND syndrome (developmental delay, epilepsy, and neonatal diabetes) and is known to respond to oral sulfonylureas. Following initiation of glibenclamide, there was significant improvement in glycemic control and a marked reduction in seizure frequency, allowing for a decrease in anti-seizure medications.Significance: This case underscores the importance of considering early clinical diagnosis and genetic testing in patients with IESS and diabetes. Identification of a KCNJ11 variant allowed for targeted treatment with sulfonylureas, which improved both metabolic and neurological outcomes.