Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina

Autores
Martin, Maria Eugenia; Intriago, Lenin; Loos, Mariana; Reyes Valenzuela, Gabriela; Veneruzzo, Gabriel Martin; Foncuberta, María Eugenia; Zelaya, Gabriela; Aschettino, Giovanna; García, Francisco; Flores, Giovanna; Caraballo, Roberto; Alonso, Cristina Noemí; Juanes, Matías Hernan
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: Infantile Epileptic Spasms Syndrome (IESS) is the most prevalent epileptic encephalopathy (EE) in the first year of life, with approximately 40 % of cases of genetic or unknown origin. This study aims to describe the clinical and molecular characteristics of a group of Argentine patients diagnosed with IESS of unknown etiology.Methods: A retrospective analysis was performed on the clinical data of 24 pediatric patients diagnosed with IESS with hypsarrhythmia, who underwent genomic studies between 2019 and 2022.Results: A genetic etiology was identified in 50 % of cases (eight boys and four girls; median seizure onset age: 3 months). Most of them initiated with IESS and over half evolved into Lennox-Gastaut syndrome. Developmental delay preceded seizure onset in all patients, persisting or worsening thereafter. Notable features included hypotonia, microcephaly, and dysmorphisms. Half of the patients had a family history of epilepsy, and two of EE. Identified variants included 7/13 (53.8 %) single nucleotide variants in KCNQ2, STXBP1, SCN8A, CDKL5, UGDH, and WWOX; 5/13 (38.5 %) copy number variants involving the genes UBE3A-GABRB3-GABRA5, SCN2A-SCN1A-SCN9A, and WWOX; and a short tandem repeat in ARX. Inheritance patterns included autosomal dominant (n = 8), recessive (n = 2), and X-linked (n = 2). Nine variants (69.2 %) were presumed de novo.Conclusion: These findings underscore the extensive genetic heterogeneity of IESS within the Argentine population, enriching the international literature and variant databases with Latin American data. In cases with an unknown cause, genetic testing is crucial in establishing an etiological diagnosis, guiding appropriate treatment, and facilitating genetic counseling.
Fil: Martin, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Intriago, Lenin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Loos, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Veneruzzo, Gabriel Martin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Foncuberta, María Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Zelaya, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aschettino, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: García, Francisco. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Flores, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
epileptic encephalopathy
Epileptic spasms
Genes
Genetic heterogeneity
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:11336/287905
Acceder
id CONICETDig_9f423307fb19dca75eec356cd183c592
oai_identifier_str oai:ri.conicet.gov.ar:11336/287905
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from ArgentinaMartin, Maria EugeniaIntriago, LeninLoos, MarianaReyes Valenzuela, GabrielaVeneruzzo, Gabriel MartinFoncuberta, María EugeniaZelaya, GabrielaAschettino, GiovannaGarcía, FranciscoFlores, GiovannaCaraballo, RobertoAlonso, Cristina NoemíJuanes, Matías Hernanepileptic encephalopathyEpileptic spasmsGenesGenetic heterogeneityhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Purpose: Infantile Epileptic Spasms Syndrome (IESS) is the most prevalent epileptic encephalopathy (EE) in the first year of life, with approximately 40 % of cases of genetic or unknown origin. This study aims to describe the clinical and molecular characteristics of a group of Argentine patients diagnosed with IESS of unknown etiology.Methods: A retrospective analysis was performed on the clinical data of 24 pediatric patients diagnosed with IESS with hypsarrhythmia, who underwent genomic studies between 2019 and 2022.Results: A genetic etiology was identified in 50 % of cases (eight boys and four girls; median seizure onset age: 3 months). Most of them initiated with IESS and over half evolved into Lennox-Gastaut syndrome. Developmental delay preceded seizure onset in all patients, persisting or worsening thereafter. Notable features included hypotonia, microcephaly, and dysmorphisms. Half of the patients had a family history of epilepsy, and two of EE. Identified variants included 7/13 (53.8 %) single nucleotide variants in KCNQ2, STXBP1, SCN8A, CDKL5, UGDH, and WWOX; 5/13 (38.5 %) copy number variants involving the genes UBE3A-GABRB3-GABRA5, SCN2A-SCN1A-SCN9A, and WWOX; and a short tandem repeat in ARX. Inheritance patterns included autosomal dominant (n = 8), recessive (n = 2), and X-linked (n = 2). Nine variants (69.2 %) were presumed de novo.Conclusion: These findings underscore the extensive genetic heterogeneity of IESS within the Argentine population, enriching the international literature and variant databases with Latin American data. In cases with an unknown cause, genetic testing is crucial in establishing an etiological diagnosis, guiding appropriate treatment, and facilitating genetic counseling.Fil: Martin, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Intriago, Lenin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Loos, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Veneruzzo, Gabriel Martin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Foncuberta, María Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Zelaya, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Aschettino, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: García, Francisco. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Flores, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caraballo, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaW B Saunders Co Ltd2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/287905Martin, Maria Eugenia; Intriago, Lenin; Loos, Mariana; Reyes Valenzuela, Gabriela; Veneruzzo, Gabriel Martin; et al.; Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina; W B Saunders Co Ltd; Seizure; 126; 3-2025; 48-571059-1311CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1059131125000317info:eu-repo/semantics/altIdentifier/doi/10.1016/j.seizure.2025.01.025info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-06-17T09:41:18Zoai:ri.conicet.gov.ar:11336/287905instacron: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:34982026-06-17 09:41:18.828CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
title Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
spellingShingle Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
Martin, Maria Eugenia
epileptic encephalopathy
Epileptic spasms
Genes
Genetic heterogeneity
title_short Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
title_full Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
title_fullStr Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
title_full_unstemmed Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
title_sort Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina
dc.creator.none.fl_str_mv Martin, Maria Eugenia
Intriago, Lenin
Loos, Mariana
Reyes Valenzuela, Gabriela
Veneruzzo, Gabriel Martin
Foncuberta, María Eugenia
Zelaya, Gabriela
Aschettino, Giovanna
García, Francisco
Flores, Giovanna
Caraballo, Roberto
Alonso, Cristina Noemí
Juanes, Matías Hernan
author Martin, Maria Eugenia
author_facet Martin, Maria Eugenia
Intriago, Lenin
Loos, Mariana
Reyes Valenzuela, Gabriela
Veneruzzo, Gabriel Martin
Foncuberta, María Eugenia
Zelaya, Gabriela
Aschettino, Giovanna
García, Francisco
Flores, Giovanna
Caraballo, Roberto
Alonso, Cristina Noemí
Juanes, Matías Hernan
author_role author
author2 Intriago, Lenin
Loos, Mariana
Reyes Valenzuela, Gabriela
Veneruzzo, Gabriel Martin
Foncuberta, María Eugenia
Zelaya, Gabriela
Aschettino, Giovanna
García, Francisco
Flores, Giovanna
Caraballo, Roberto
Alonso, Cristina Noemí
Juanes, Matías Hernan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv epileptic encephalopathy
Epileptic spasms
Genes
Genetic heterogeneity
topic epileptic encephalopathy
Epileptic spasms
Genes
Genetic heterogeneity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: Infantile Epileptic Spasms Syndrome (IESS) is the most prevalent epileptic encephalopathy (EE) in the first year of life, with approximately 40 % of cases of genetic or unknown origin. This study aims to describe the clinical and molecular characteristics of a group of Argentine patients diagnosed with IESS of unknown etiology.Methods: A retrospective analysis was performed on the clinical data of 24 pediatric patients diagnosed with IESS with hypsarrhythmia, who underwent genomic studies between 2019 and 2022.Results: A genetic etiology was identified in 50 % of cases (eight boys and four girls; median seizure onset age: 3 months). Most of them initiated with IESS and over half evolved into Lennox-Gastaut syndrome. Developmental delay preceded seizure onset in all patients, persisting or worsening thereafter. Notable features included hypotonia, microcephaly, and dysmorphisms. Half of the patients had a family history of epilepsy, and two of EE. Identified variants included 7/13 (53.8 %) single nucleotide variants in KCNQ2, STXBP1, SCN8A, CDKL5, UGDH, and WWOX; 5/13 (38.5 %) copy number variants involving the genes UBE3A-GABRB3-GABRA5, SCN2A-SCN1A-SCN9A, and WWOX; and a short tandem repeat in ARX. Inheritance patterns included autosomal dominant (n = 8), recessive (n = 2), and X-linked (n = 2). Nine variants (69.2 %) were presumed de novo.Conclusion: These findings underscore the extensive genetic heterogeneity of IESS within the Argentine population, enriching the international literature and variant databases with Latin American data. In cases with an unknown cause, genetic testing is crucial in establishing an etiological diagnosis, guiding appropriate treatment, and facilitating genetic counseling.
Fil: Martin, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Intriago, Lenin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Loos, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Veneruzzo, Gabriel Martin. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Foncuberta, María Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Zelaya, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aschettino, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: García, Francisco. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Flores, Giovanna. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Alonso, Cristina Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Purpose: Infantile Epileptic Spasms Syndrome (IESS) is the most prevalent epileptic encephalopathy (EE) in the first year of life, with approximately 40 % of cases of genetic or unknown origin. This study aims to describe the clinical and molecular characteristics of a group of Argentine patients diagnosed with IESS of unknown etiology.Methods: A retrospective analysis was performed on the clinical data of 24 pediatric patients diagnosed with IESS with hypsarrhythmia, who underwent genomic studies between 2019 and 2022.Results: A genetic etiology was identified in 50 % of cases (eight boys and four girls; median seizure onset age: 3 months). Most of them initiated with IESS and over half evolved into Lennox-Gastaut syndrome. Developmental delay preceded seizure onset in all patients, persisting or worsening thereafter. Notable features included hypotonia, microcephaly, and dysmorphisms. Half of the patients had a family history of epilepsy, and two of EE. Identified variants included 7/13 (53.8 %) single nucleotide variants in KCNQ2, STXBP1, SCN8A, CDKL5, UGDH, and WWOX; 5/13 (38.5 %) copy number variants involving the genes UBE3A-GABRB3-GABRA5, SCN2A-SCN1A-SCN9A, and WWOX; and a short tandem repeat in ARX. Inheritance patterns included autosomal dominant (n = 8), recessive (n = 2), and X-linked (n = 2). Nine variants (69.2 %) were presumed de novo.Conclusion: These findings underscore the extensive genetic heterogeneity of IESS within the Argentine population, enriching the international literature and variant databases with Latin American data. In cases with an unknown cause, genetic testing is crucial in establishing an etiological diagnosis, guiding appropriate treatment, and facilitating genetic counseling.
publishDate 2025
dc.date.none.fl_str_mv 2025-03
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/11336/287905
Martin, Maria Eugenia; Intriago, Lenin; Loos, Mariana; Reyes Valenzuela, Gabriela; Veneruzzo, Gabriel Martin; et al.; Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina; W B Saunders Co Ltd; Seizure; 126; 3-2025; 48-57
1059-1311
CONICET Digital
CONICET
url http://hdl.handle.net/11336/287905
identifier_str_mv Martin, Maria Eugenia; Intriago, Lenin; Loos, Mariana; Reyes Valenzuela, Gabriela; Veneruzzo, Gabriel Martin; et al.; Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina; W B Saunders Co Ltd; Seizure; 126; 3-2025; 48-57
1059-1311
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1059131125000317
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.seizure.2025.01.025
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
application/pdf
dc.publisher.none.fl_str_mv W B Saunders Co Ltd
publisher.none.fl_str_mv W B Saunders Co Ltd
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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score 13.040872

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