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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/17587
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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) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |