biostudies-literatureZaman TNational Institute of Neurological Disorders and StrokeBurroughs Wellcome FundJapan Agency for Medical Research and DevelopmentMarch of Dimes FoundationNINDS NIH HHSEuropean Cooperation in Science and TechnologyWellcome TrustJapan Society for the Promotion of Science348-362https://www.ebi.ac.uk/biostudies/studies/S-EPMC8552104biostudies-literatureUnknown88(2)<h4>Objective</h4>Pathogenic variants in SCN3A, encoding the voltage-gated sodium channel subunit Nav1.3, cause severe childhood onset epilepsy and malformation of cortical development. Here, we define the spectrum of clinical, genetic, and neuroimaging features of SCN3A-related neurodevelopmental disorder.<h4>Methods</h4>Patients were ascertained via an international collaborative network. We compared sodium channels containing wild-type versus variant Nav1.3 subunits coexpressed with β1 and β2 subunits using whole-cell voltage clamp electrophysiological recordings in a heterologous mammalian system (HEK-293T cells).<h4>Results</h4>Of 22 patients with pathogenic SCN3A variants, most had treatment-resistant epilepsy beginning in the first year of life (16/21, 76%; median onset, 2 weeks), wAnnals of neurologySCN3A-Related Neurodevelopmental Disorder: A Spectrum of Epilepsy and Brain Malformation.PMC8552104R01 NS119977JP19ek0109280JP18kk020501K08 NS097633Career Award for Medical ScientistsWT098051Basil O&apos;Connor Research AwardJP19dm0107090JP19ek0109348Action 16118 (European Network on Brain MalformatiJP17K10080JP17H01539JP19ek0109301Marom DZaman TThompson CHFujiwara YCharzewska AHarrison VHelbig IStouffs KHelbig KLJansen AESrinivasan SGuerrini RHoffman-Zacharska DGoldberg EMBassan HKang SKJoss SPilz DTVasudevan PParrini EFry AEClatot JAckermann SJacquinet AHauser NReish OSpencer CEMiyatake SFawcett KALippa NFitzpatrick DKearney JAVerstraete LBen-Zeev BVu TAMatsumoto NfalseSCN3A-Related Neurodevelopmental Disorder: A Spectrum of Epilepsy and Brain Malformation.<h4>Objective</h4>Pathogenic variants in SCN3A, encoding the voltage-gated sodium channel subunit Nav1.3, cause severe childhood onset epilepsy and malformation of cortical development. Here, we define the spectrum of clinical, genetic, and neuroimaging features of SCN3A-related neurodevelopmental disorder.<h4>Methods</h4>Patients were ascertained via an international collaborative network. We compared sodium channels containing wild-type versus variant Nav1.3 subunits coexpressed with β1 and β2 subunits using whole-cell voltage clamp electrophysiological recordings in a heterologous mammalian system (HEK-293T cells).<h4>Results</h4>Of 22 patients with pathogenic SCN3A variants, most had treatment-resistant epilepsy beginning in the first year of life (16/21, 76%; median onset, 2 weeks), w2020-01-01T00:00:00Z2020 Aug2025-04-18T19:11:23.481Z2025-04-07T06:54:39.106ZS-EPMC85521043251501710.1002/ana.25809