Phenotypic variability from benign infantile epilepsy to Ohtahara syndrome associated with a novel mutation in SCN2A

• Verfasst von: Syrbe, Steffen [VerfasserIn]
• Verfasst von: Mütze, Ulrike [VerfasserIn]
• Titel: Phenotypic variability from benign infantile epilepsy to Ohtahara syndrome associated with a novel mutation in SCN2A
• Verf.angabe: Steffen Syrbe, Boris S. Zhorov, Astrid Bertsche, Matthias K. Bernhard, Frauke Hornemann, Ulrike Mütze, Jessica Hoffmann, Konstanze Hörtnagel, Wieland Kiess, Franz W. Hirsch, Johannes R. Lemke, Andreas Merkenschlager
• E-Jahr: 2016
• Jahr: July 19, 2016
• Umfang: 7 S.
• Fussnoten: Gesehen am 26.05.2020
• Titel Quelle: Enthalten in: Molecular syndromology
• Ort Quelle: Basel : Karger, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 4, Seite 182-188
• ISSN Quelle: 1661-8777
• DOI: doi:10.1159/000447526
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698835159

Abstract

Mutations in <i>SCN2A</i> have been associated with benign familial neonatal-infantile seizures (BFNIS) as well as infantile-onset epileptic encephalopathy, such as Ohtahara syndrome (OS). We describe a family with 3 affected individuals carrying the novel <i>SCN2A</i> missense variant c.1147C>G, p.Q383E affecting a residue proximal to the highly conserved selectivity filter in the P-loop of the voltage-gated sodium channel (Na_v1.2). All 3 individuals presented with seizures in early infancy. However, there were striking differences in the spectrum of clinical presentations, ranging from BFNIS to OS. A change of ion selectivity of Na_v1.2 is considered to be the potential pathomechanism underlying this Na_v1.2 channel dysfunction. The observation of benign and severe phenotypes due to an identical mutation within one family contradicts the hypothesis of different modes of inheritance as a mandatory feature discriminating BFNIS from <i>SCN2A</i> encephalopathy.