Neurodevelopmental disorder associated with de novo SCN3A pathogenic variants: two new cases and review of the literature

• Published in: Brain & development (Tokyo. 1979) Vol. 42; no. 2; pp. 211 - 216
• Main Authors: Inuzuka, Luciana Midori, Macedo-Souza, Lúcia Inês, Della-Ripa, Bruno, Cabral, Katiane S.S., Monteiro, Fabiola, Kitajima, João Paulo, de Souza Godoy, Luis Filipe, de Souza Delgado, Daniel, Kok, Fernando, Garzon, Eliana
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2020
• Subjects: Child, Preschool; Epilepsy; Epilepsy - genetics; Epileptic encephalopathy; Female; Genotype; Humans; Intellectual Disability - genetics; Magnetic Resonance Imaging; Male; Mutation - genetics; NAV1.3 Voltage-Gated Sodium Channel - genetics; NAV1.3 Voltage-Gated Sodium Channel - metabolism; Neurodevelopmental Disorders - genetics; Neurodevelopmental Disorders - physiopathology; Phenotype; Polymicrogyria; Polymicrogyria - genetics; SCN3A; Sodium Channels - genetics; Sodium Channels - metabolism; Polymicrogyria; Epileptic encephalopathy; SCN3A; Epilepsy
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2019.09.004

SCN3A was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. We present two additional patients with a novel de novo SCN3A pathogenic variant, and a review of all published cases of de novo variants. In one of our patients brain magnetic resonance imaging (MRI) disclosed a severe polymicrogyria and in the other it was normal. The clinical phenotype was characterized by a severe developmental delay and refractory epilepsy in the patient with polymicrogyria and intellectual disability with autistic features and pharmacoresponsive epilepsy in the subject with normal MRI. Polymicrogyria, a disorder of progenitor cells proliferation and migration, is an unanticipated finding for an ion channel dysfunction.