title: Autosomal dominant SCN8A mutation with an unusually mild phenotype.
abstract: BACKGROUND
  Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13.
  
  
  METHODS
  Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers.
  
  
  CONCLUSIONS
  Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors.
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK. Electronic address: Geetha.Anand@ouh.nhs.uk.
authors.forename: G
authors.initials: G
authors.lastname: Anand
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK.
authors.forename: F
authors.initials: F
authors.lastname: Collett-White
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Orsini
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Royal Berkshire Hospital, Reading, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jayapal
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Trump
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Zaiwalla
authors.affiliation: Department of Paediatric Neurology, Oxford Children's Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jayawant
mesh_terms: D000328:Adult; D020936:Epilepsy, Benign Neonatal / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D009154:Mutation; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; C100681:SCN8A protein, human
keywords: Benign familial infantile epilepsy; Focal epilepsy; Next generation sequence analysis; SCN8A; Voltage-gated sodium channels