title: The clinical utility of an SCN1A genetic diagnosis in infantile-onset epilepsy.
abstract: OBJECTIVE
  Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives.
  
  
  METHODS
  Participants were identified prospectively from referrals to the Epilepsy Genetics Service in Glasgow and contacted via their referring clinicians. Questionnaires exploring the consequences of SCN1A genetic testing for each case were sent to carers and physicians.
  
  
  RESULTS
  Of the 244 individuals contacted, 182 (75%) carried a SCN1A mutation. Carers of 187 (77%) patients responded (90 females, 97 males; mean age at referral 4 y 10 mo; interquartile range 9 y 1 mo). Of those participants whose children tested positive for a mutation, 87% reported that genetic testing was helpful, leading to treatment changes resulting in fewer seizures and improved access to therapies and respite care. Out of 187 physicians, 163 responded (87%), of whom 48% reported that a positive test facilitated diagnosis earlier than with clinical and electroencephalography data alone. It prevented additional investigations in 67% of patients, altered treatment approach in 69%, influenced medication choice in 74%, and, through medication change, improved seizure control in 42%.
  
  
  CONCLUSIONS
  In addition to confirming a clinical diagnosis, a positive SCN1A test result influenced treatment choice and assisted in accessing additional therapies, especially in the very young.
authors.affiliation:  The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brunklaus
authors.affiliation:  The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow.
authors.forename: Liam
authors.initials: L
authors.lastname: Dorris
authors.affiliation:  Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children, Glasgow.
authors.forename: Rachael
authors.initials: R
authors.lastname: Ellis
authors.affiliation:  Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children, Glasgow.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Reavey
authors.affiliation:  The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lee
authors.affiliation:  Duncan Guthrie Institute of Medical Genetics, Royal Hospital for Sick Children, Glasgow.
authors.forename: Gordon
authors.initials: G
authors.lastname: Forbes
authors.affiliation:  Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool.
authors.forename: Richard
authors.initials: R
authors.lastname: Appleton
authors.affiliation:  Neurosciences Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation:  Department of Paediatric Neurology, Leeds General Infirmary, Leeds.
authors.forename: Colin
authors.initials: C
authors.lastname: Ferrie
authors.affiliation:  Department of Paediatric Neurology, Royal Manchester Children's Hospital, Manchester.
authors.forename: Imelda
authors.initials: I
authors.lastname: Hughes
authors.affiliation:  Tayside Children's Hospital and Child Health, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Jollands
authors.affiliation:  Paediatric Neurology Department, Children's University Hospital Temple Street, Dublin, Ireland.
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
authors.affiliation:  Department of Paediatric Neurology, Leeds General Infirmary, Leeds.
authors.forename: John
authors.initials: J
authors.lastname: Livingston
authors.affiliation:  Paediatric Neurology Department, Children's University Hospital Temple Street, Dublin, Ireland.
authors.forename: Bryan
authors.initials: B
authors.lastname: Lynch
authors.affiliation:  Neurology Department, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Sunny
authors.initials: S
authors.lastname: Philip
authors.affiliation:  Departments of Medicine and Paediatrics, Florey Neurosciences Institute, The University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Vic., Australia.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.affiliation:  Department of Paediatric Neurology, Evelina Children's Hospital, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Williams
authors.affiliation:  The Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow.
authors.forename: Sameer M
authors.initials: SM
authors.lastname: Zuberi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000175:diagnosis* / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D010818:Practice Patterns, Physicians'; D011795:Surveys and Questionnaires
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human