{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:03:48Z","timestamp":1791115428517,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T00:00:00Z","timestamp":1365984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>This report is a practical reference guide for genetic testing of <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic>, the gene encoding the \u03b11 subunit of neuronal voltage\u2010gated sodium channels (protein name: Na<jats:sub>v<\/jats:sub>1.1). Mutations in this gene are frequently found in Dravet syndrome (<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>), and are sometimes found in genetic epilepsy with febrile seizures plus (<jats:styled-content style=\"fixed-case\">GEFS<\/jats:styled-content>+), migrating partial seizures of infancy (<jats:styled-content style=\"fixed-case\">MPSI<\/jats:styled-content>), other infantile epileptic encephalopathies, and rarely in infantile spasms. <jats:italic>Recommendations for testing<\/jats:italic>: (1) Testing is particularly useful for people with suspected <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> and sometimes in other early onset infantile epileptic encephalopathies such as <jats:styled-content style=\"fixed-case\">MPSI<\/jats:styled-content> because genetic confirmation of the clinical diagnosis may allow optimization of antiepileptic therapy with the potential to improve seizure control and developmental outcome. In addition, a molecular diagnosis may prevent the need for unnecessary investigations, as well as inform genetic counseling. (2) <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> testing should be considered in people with possible <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> where the typical initial presentation is of a developmentally normal infant presenting with recurrent, febrile or afebrile prolonged, hemiclonic seizures or generalized status epilepticus. After age 2, the clinical diagnosis of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, the clinical utility of <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> testing for <jats:styled-content style=\"fixed-case\">GEFS<\/jats:styled-content>+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. <jats:italic>Interpreting test results<\/jats:italic>: (1) Mutational testing of <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> involves both conventional <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing of the coding regions and analyses to detect genomic rearrangements within the relevant chromosomal region: 2q24. Interpretation of the test results must always be done in the context of the electroclinical syndrome and often requires the assistance of a medical geneticist, since many genomic variations are possible and it is essential to differentiate benign polymorphisms from pathogenic mutations. (2) Missense variants may have no apparent effect on the phenotype (benign polymorphisms) or may represent mutations underlying <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> MPSI<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> GEFS<\/jats:styled-content>+, and related syndromes and can provide a challenge in interpretation. (3) Conventional methods do not detect variations in introns or promoter or regulatory regions; therefore, a negative test does not exclude a pathogenic role of <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> or other conditions because genes other than <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic> may be involved. Obtaining written informed consent and genetic counseling should be considered prior to molecular testing, depending on the clinical situation and local regulations.<\/jats:p>","DOI":"10.1111\/epi.12168","type":"journal-article","created":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T18:22:28Z","timestamp":1366050148000},"page":"946-952","source":"Crossref","is-referenced-by-count":69,"title":["<i>SCN1A<\/i> testing for epilepsy: Application in clinical practice"],"prefix":"10.1111","volume":"54","author":[{"given":"Shinichi","family":"Hirose","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Research Institute for the Molecular Pathomechanisms of Epilepsy Fukuoka University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Florey Institute Departments of Medicine and Paediatrics Austin Health and Royal Children's Hospital University of Melbourne Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Marini","sequence":"additional","affiliation":[{"name":"Epilepsy, Neurophysiology and Neurogenetics Unit Division of Child Neurology and Psychiatry University of Pisa and Research Institute Stella Maris Foundation Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"De Jonghe","sequence":"additional","affiliation":[{"name":"Neurogenetics Group VIB\u2010Department of Molecular Genetics and Laboratory of Neurogenetics Institute Born\u2010Bunge University of Antwerp Antwerpen Belgium"},{"name":"Department of Neurology Antwerp University Hospital Antwerpen Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Andermann","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit Montreal Neurological Hospital &amp; Institute Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alica M.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Neurology Baylor College of Medicine Houston Texas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Kauffman","sequence":"additional","affiliation":[{"name":"Neurogenetics Clinic Hospital JM Ramos Mejia University of Buenos Aires\u2010CONICET Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel C. 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