Open AccessPhenotypic Variability from Benign Infantile Epilepsy to Ohtahara Syndrome Associated with a Novel Mutation in SCN2A
Author(s) -
Steffen Syrbe,
Boris S. Zhorov,
Astrid Bertsche,
Matthias K. Bernhard,
Frauke Hornemann,
Ulrike Mütze,
Jessica Hoffmann,
Konstanze Hörtnagel,
Wieland Kieß,
Wolfgang Hirsch,
Johannes R. Lemke,
Andreas Merkenschlager
Publication year - 2016
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000447526
Subject(s) - missense mutation , epilepsy , phenotype , medicine , mutation , sodium channel , encephalopathy , dravet syndrome , genetics , biology , gene , sodium , chemistry , organic chemistry , psychiatry
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 (Na v 1.2). 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 v 1.2 is considered to be the potential pathomechanism underlying this Na v 1.2 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.