Key result
Novel SCN2A missense variant linked to highly variable phenotypes from benign seizures to Ohtahara syndrome.
Case Report (n=3)
An identical SCN2A mutation can cause both benign and severe epilepsy phenotypes within the same family, contradicting the hypothesis that different modes of inheritance discriminate BFNIS from SCN2A encephalopathy.
Expands SCN2A epilepsy spectrum; hypothesis-generating and should not yet change diagnostics or management.
Mutations in SCN2A 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 SCN2A 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 (Nav1.2). 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 Nav1.2 is considered to be the potential pathomechanism underlying this Nav1.2 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 SCN2A encephalopathy.
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Syrbe et al. (2016) conducted a case report in SCN2A mutation-associated epilepsy (n=3). SCN2A missense variant c.1147C>G, p.Q383E was evaluated on Clinical phenotype. A novel SCN2A missense variant (c.1147C>G, p.Q383E) in one family caused highly variable phenotypes ranging from benign familial neonatal-infantile seizures to severe Ohtahara syndrome.