SCN1A testing for epilepsy: application in clinical practice

Autores
Hirose, Shinichi; Scheffer, Ingrid E.; Marini, Carla; De Jonghe, Peter; Andermann, Eva; Goldman, Alica M.; Kauffman, Marcelo Andres; Tan, Nigel C. K.; Lowenstein, Daniel H.; Sisodiya, Sanjay M.; Ottman, Ruth; Berkovic, Samuel F.; The Genetics Commission of the International League Against Epilepsy
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage-gated sodium channels (protein name: Nav1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI 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) SCN1A testing should be considered in people with possible DS 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 DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA 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 DS, MPSI, GEFS+, 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 SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A 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.
Fil: Hirose, Shinichi. Fukuoka University; Japón
Fil: Scheffer, Ingrid E.. The University of Melbourne; Australia
Fil: Marini, Carla. Università degli Studi di Pisa; Italia
Fil: De Jonghe, Peter. Universiteit Antwerpen; Bélgica
Fil: Andermann, Eva. McGill University. Montreal Neurological Institute and Hospital; Canadá
Fil: Goldman, Alica M.. Baylor College of Medicine; Estados Unidos
Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Tan, Nigel C. K.. National Neuroscience Institute; Singapur
Fil: Lowenstein, Daniel H.. University of California; Estados Unidos
Fil: Sisodiya, Sanjay M.. University College London; Estados Unidos. Epilepsy Society; Reino Unido
Fil: Ottman, Ruth. Columbia University; Estados Unidos
Fil: Berkovic, Samuel F.. The University of Melbourne; Australia
Fil: The Genetics Commission of the International League Against Epilepsy.
Materia
Genetic
Epilepsy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/17587

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network_name_str CONICET Digital (CONICET)
spelling SCN1A testing for epilepsy: application in clinical practiceHirose, ShinichiScheffer, Ingrid E.Marini, CarlaDe Jonghe, PeterAndermann, EvaGoldman, Alica M.Kauffman, Marcelo AndresTan, Nigel C. K.Lowenstein, Daniel H.Sisodiya, Sanjay M.Ottman, RuthBerkovic, Samuel F.The Genetics Commission of the International League Against EpilepsyGeneticEpilepsyhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage-gated sodium channels (protein name: Nav1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI 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) SCN1A testing should be considered in people with possible DS 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 DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA 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 DS, MPSI, GEFS+, 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 SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A 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.Fil: Hirose, Shinichi. Fukuoka University; JapónFil: Scheffer, Ingrid E.. The University of Melbourne; AustraliaFil: Marini, Carla. Università degli Studi di Pisa; ItaliaFil: De Jonghe, Peter. Universiteit Antwerpen; BélgicaFil: Andermann, Eva. McGill University. Montreal Neurological Institute and Hospital; CanadáFil: Goldman, Alica M.. Baylor College of Medicine; Estados UnidosFil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Tan, Nigel C. K.. National Neuroscience Institute; SingapurFil: Lowenstein, Daniel H.. University of California; Estados UnidosFil: Sisodiya, Sanjay M.. University College London; Estados Unidos. Epilepsy Society; Reino UnidoFil: Ottman, Ruth. Columbia University; Estados UnidosFil: Berkovic, Samuel F.. The University of Melbourne; AustraliaFil: The Genetics Commission of the International League Against Epilepsy.Wiley2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17587Hirose, Shinichi; Scheffer, Ingrid E.; Marini, Carla; De Jonghe, Peter; Andermann, Eva; et al.; SCN1A testing for epilepsy: application in clinical practice; Wiley; Epilepsia; 54; 5; 5-2013; 946-9520013-95801528-1167enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/epi.12168/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/epi.12168info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:05Zoai:ri.conicet.gov.ar:11336/17587instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:14:06.179CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SCN1A testing for epilepsy: application in clinical practice
title SCN1A testing for epilepsy: application in clinical practice
spellingShingle SCN1A testing for epilepsy: application in clinical practice
Hirose, Shinichi
Genetic
Epilepsy
title_short SCN1A testing for epilepsy: application in clinical practice
title_full SCN1A testing for epilepsy: application in clinical practice
title_fullStr SCN1A testing for epilepsy: application in clinical practice
title_full_unstemmed SCN1A testing for epilepsy: application in clinical practice
title_sort SCN1A testing for epilepsy: application in clinical practice
dc.creator.none.fl_str_mv Hirose, Shinichi
Scheffer, Ingrid E.
Marini, Carla
De Jonghe, Peter
Andermann, Eva
Goldman, Alica M.
Kauffman, Marcelo Andres
Tan, Nigel C. K.
Lowenstein, Daniel H.
Sisodiya, Sanjay M.
Ottman, Ruth
Berkovic, Samuel F.
The Genetics Commission of the International League Against Epilepsy
author Hirose, Shinichi
author_facet Hirose, Shinichi
Scheffer, Ingrid E.
Marini, Carla
De Jonghe, Peter
Andermann, Eva
Goldman, Alica M.
Kauffman, Marcelo Andres
Tan, Nigel C. K.
Lowenstein, Daniel H.
Sisodiya, Sanjay M.
Ottman, Ruth
Berkovic, Samuel F.
The Genetics Commission of the International League Against Epilepsy
author_role author
author2 Scheffer, Ingrid E.
Marini, Carla
De Jonghe, Peter
Andermann, Eva
Goldman, Alica M.
Kauffman, Marcelo Andres
Tan, Nigel C. K.
Lowenstein, Daniel H.
Sisodiya, Sanjay M.
Ottman, Ruth
Berkovic, Samuel F.
The Genetics Commission of the International League Against Epilepsy
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genetic
Epilepsy
topic Genetic
Epilepsy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage-gated sodium channels (protein name: Nav1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI 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) SCN1A testing should be considered in people with possible DS 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 DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA 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 DS, MPSI, GEFS+, 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 SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A 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.
Fil: Hirose, Shinichi. Fukuoka University; Japón
Fil: Scheffer, Ingrid E.. The University of Melbourne; Australia
Fil: Marini, Carla. Università degli Studi di Pisa; Italia
Fil: De Jonghe, Peter. Universiteit Antwerpen; Bélgica
Fil: Andermann, Eva. McGill University. Montreal Neurological Institute and Hospital; Canadá
Fil: Goldman, Alica M.. Baylor College of Medicine; Estados Unidos
Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Tan, Nigel C. K.. National Neuroscience Institute; Singapur
Fil: Lowenstein, Daniel H.. University of California; Estados Unidos
Fil: Sisodiya, Sanjay M.. University College London; Estados Unidos. Epilepsy Society; Reino Unido
Fil: Ottman, Ruth. Columbia University; Estados Unidos
Fil: Berkovic, Samuel F.. The University of Melbourne; Australia
Fil: The Genetics Commission of the International League Against Epilepsy.
description This report is a practical reference guide for genetic testing of SCN1A, the gene encoding the α1 subunit of neuronal voltage-gated sodium channels (protein name: Nav1.1). Mutations in this gene are frequently found in Dravet syndrome (DS), and are sometimes found in genetic epilepsy with febrile seizures plus (GEFS+), migrating partial seizures of infancy (MPSI), other infantile epileptic encephalopathies, and rarely in infantile spasms. Recommendations for testing: (1) Testing is particularly useful for people with suspected DS and sometimes in other early onset infantile epileptic encephalopathies such as MPSI 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) SCN1A testing should be considered in people with possible DS 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 DS becomes more obvious, with the classical evolution of other seizure types and developmental slowing. (3) In contrast to DS, the clinical utility of SCN1A testing for GEFS+ remains questionable. (4) The test is not recommended for children with phenotypes that are not clearly associated with SCN1A mutations such as those characterized by abnormal development or neurologic deficits apparent at birth or structural abnormalities of the brain. Interpreting test results: (1) Mutational testing of SCN1A involves both conventional DNA 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 DS, MPSI, GEFS+, 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 SCN1A in a specific phenotype. (4) It is important to note that a negative test does not rule out the clinical diagnosis of DS or other conditions because genes other than SCN1A 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/17587
Hirose, Shinichi; Scheffer, Ingrid E.; Marini, Carla; De Jonghe, Peter; Andermann, Eva; et al.; SCN1A testing for epilepsy: application in clinical practice; Wiley; Epilepsia; 54; 5; 5-2013; 946-952
0013-9580
1528-1167
url http://hdl.handle.net/11336/17587
identifier_str_mv Hirose, Shinichi; Scheffer, Ingrid E.; Marini, Carla; De Jonghe, Peter; Andermann, Eva; et al.; SCN1A testing for epilepsy: application in clinical practice; Wiley; Epilepsia; 54; 5; 5-2013; 946-952
0013-9580
1528-1167
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/epi.12168/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/epi.12168
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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