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Epilepsy Course and Developmental Trajectories in STXBP1-DEE
BACKGROUND AND OBJECTIVES: Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between n...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157582/ https://www.ncbi.nlm.nih.gov/pubmed/35655584 http://dx.doi.org/10.1212/NXG.0000000000000676 |
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author | Balagura, Ganna Xian, Julie Riva, Antonella Marchese, Francesca Ben Zeev, Bruria Rios, Loreto Sirsi, Deepa Accorsi, Patrizia Amadori, Elisabetta Astrea, Guja Baldassari, Simona Beccaria, Francesca Boni, Antonella Budetta, Mauro Cantalupo, Gaetano Capovilla, Giuseppe Cesaroni, Elisabetta Chiesa, Valentina Coppola, Antonietta Dilena, Robertino Faggioli, Raffaella Ferrari, Annarita Fiorini, Elena Madia, Francesca Gennaro, Elena Giacomini, Thea Giordano, Lucio Iacomino, Michele Lattanzi, Simona Marini, Carla Mancardi, Maria Margherita Mastrangelo, Massimo Messana, Tullio Minetti, Carlo Nobili, Lino Papa, Amanda Parmeggiani, Antonia Pisano, Tiziana Russo, Angelo Salpietro, Vincenzo Savasta, Salvatore Scala, Marcello Accogli, Andrea Scelsa, Barbara Scudieri, Paolo Spalice, Alberto Specchio, Nicola Trivisano, Marina Tzadok, Michal Valeriani, Massimiliano Vari, Maria Stella Verrotti, Alberto Vigevano, Federico Vignoli, Aglaia Toonen, Ruud Zara, Federico Helbig, Ingo Striano, Pasquale |
author_facet | Balagura, Ganna Xian, Julie Riva, Antonella Marchese, Francesca Ben Zeev, Bruria Rios, Loreto Sirsi, Deepa Accorsi, Patrizia Amadori, Elisabetta Astrea, Guja Baldassari, Simona Beccaria, Francesca Boni, Antonella Budetta, Mauro Cantalupo, Gaetano Capovilla, Giuseppe Cesaroni, Elisabetta Chiesa, Valentina Coppola, Antonietta Dilena, Robertino Faggioli, Raffaella Ferrari, Annarita Fiorini, Elena Madia, Francesca Gennaro, Elena Giacomini, Thea Giordano, Lucio Iacomino, Michele Lattanzi, Simona Marini, Carla Mancardi, Maria Margherita Mastrangelo, Massimo Messana, Tullio Minetti, Carlo Nobili, Lino Papa, Amanda Parmeggiani, Antonia Pisano, Tiziana Russo, Angelo Salpietro, Vincenzo Savasta, Salvatore Scala, Marcello Accogli, Andrea Scelsa, Barbara Scudieri, Paolo Spalice, Alberto Specchio, Nicola Trivisano, Marina Tzadok, Michal Valeriani, Massimiliano Vari, Maria Stella Verrotti, Alberto Vigevano, Federico Vignoli, Aglaia Toonen, Ruud Zara, Federico Helbig, Ingo Striano, Pasquale |
author_sort | Balagura, Ganna |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between neurodevelopment and epilepsy. METHODS: Retrospective standardized clinical data were collected through international collaboration. A composite neurodevelopmental score system compared the developmental trajectories in STXBP1-DEE. RESULTS: Forty-eight patients with de novo STXBP1 variants and a history of epilepsy were included (age range at the time of the study: 10 months to 35 years, mean 8.5 years). At the time of inclusion, 65% of individuals (31/48) had active epilepsy, whereas 35% (17/48) were seizure free, and 76% of those (13/17) achieved remission within the first year of life. Twenty-two individuals (46%) showed signs of developmental impairment and/or neurologic abnormalities before epilepsy onset. Age at seizure onset correlated with severity of developmental outcome and the developmental milestones achieved, with a later seizure onset associated with better developmental outcome. In contrast, age at seizure remission and epilepsy duration did not affect neurodevelopmental outcomes. Overall, we did not observe a clear genotype-phenotype correlation, but monozygotic twins with de novo STXBP1 variant showed similar phenotype and parallel disease course. DISCUSSION: The disease course in STXBP1-DEE presents with 2 main trajectories, with either early seizure remission or drug-resistant epilepsy, and a range of neurodevelopmental outcomes from mild to profound intellectual disability. Age at seizure onset is the only epilepsy-related feature associated with neurodevelopment outcome. These findings can inform future dedicated natural history studies and trial design. |
format | Online Article Text |
id | pubmed-9157582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wolters Kluwer |
record_format | MEDLINE/PubMed |
spelling | pubmed-91575822022-06-01 Epilepsy Course and Developmental Trajectories in STXBP1-DEE Balagura, Ganna Xian, Julie Riva, Antonella Marchese, Francesca Ben Zeev, Bruria Rios, Loreto Sirsi, Deepa Accorsi, Patrizia Amadori, Elisabetta Astrea, Guja Baldassari, Simona Beccaria, Francesca Boni, Antonella Budetta, Mauro Cantalupo, Gaetano Capovilla, Giuseppe Cesaroni, Elisabetta Chiesa, Valentina Coppola, Antonietta Dilena, Robertino Faggioli, Raffaella Ferrari, Annarita Fiorini, Elena Madia, Francesca Gennaro, Elena Giacomini, Thea Giordano, Lucio Iacomino, Michele Lattanzi, Simona Marini, Carla Mancardi, Maria Margherita Mastrangelo, Massimo Messana, Tullio Minetti, Carlo Nobili, Lino Papa, Amanda Parmeggiani, Antonia Pisano, Tiziana Russo, Angelo Salpietro, Vincenzo Savasta, Salvatore Scala, Marcello Accogli, Andrea Scelsa, Barbara Scudieri, Paolo Spalice, Alberto Specchio, Nicola Trivisano, Marina Tzadok, Michal Valeriani, Massimiliano Vari, Maria Stella Verrotti, Alberto Vigevano, Federico Vignoli, Aglaia Toonen, Ruud Zara, Federico Helbig, Ingo Striano, Pasquale Neurol Genet Research Article BACKGROUND AND OBJECTIVES: Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between neurodevelopment and epilepsy. METHODS: Retrospective standardized clinical data were collected through international collaboration. A composite neurodevelopmental score system compared the developmental trajectories in STXBP1-DEE. RESULTS: Forty-eight patients with de novo STXBP1 variants and a history of epilepsy were included (age range at the time of the study: 10 months to 35 years, mean 8.5 years). At the time of inclusion, 65% of individuals (31/48) had active epilepsy, whereas 35% (17/48) were seizure free, and 76% of those (13/17) achieved remission within the first year of life. Twenty-two individuals (46%) showed signs of developmental impairment and/or neurologic abnormalities before epilepsy onset. Age at seizure onset correlated with severity of developmental outcome and the developmental milestones achieved, with a later seizure onset associated with better developmental outcome. In contrast, age at seizure remission and epilepsy duration did not affect neurodevelopmental outcomes. Overall, we did not observe a clear genotype-phenotype correlation, but monozygotic twins with de novo STXBP1 variant showed similar phenotype and parallel disease course. DISCUSSION: The disease course in STXBP1-DEE presents with 2 main trajectories, with either early seizure remission or drug-resistant epilepsy, and a range of neurodevelopmental outcomes from mild to profound intellectual disability. Age at seizure onset is the only epilepsy-related feature associated with neurodevelopment outcome. These findings can inform future dedicated natural history studies and trial design. Wolters Kluwer 2022-05-31 /pmc/articles/PMC9157582/ /pubmed/35655584 http://dx.doi.org/10.1212/NXG.0000000000000676 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Research Article Balagura, Ganna Xian, Julie Riva, Antonella Marchese, Francesca Ben Zeev, Bruria Rios, Loreto Sirsi, Deepa Accorsi, Patrizia Amadori, Elisabetta Astrea, Guja Baldassari, Simona Beccaria, Francesca Boni, Antonella Budetta, Mauro Cantalupo, Gaetano Capovilla, Giuseppe Cesaroni, Elisabetta Chiesa, Valentina Coppola, Antonietta Dilena, Robertino Faggioli, Raffaella Ferrari, Annarita Fiorini, Elena Madia, Francesca Gennaro, Elena Giacomini, Thea Giordano, Lucio Iacomino, Michele Lattanzi, Simona Marini, Carla Mancardi, Maria Margherita Mastrangelo, Massimo Messana, Tullio Minetti, Carlo Nobili, Lino Papa, Amanda Parmeggiani, Antonia Pisano, Tiziana Russo, Angelo Salpietro, Vincenzo Savasta, Salvatore Scala, Marcello Accogli, Andrea Scelsa, Barbara Scudieri, Paolo Spalice, Alberto Specchio, Nicola Trivisano, Marina Tzadok, Michal Valeriani, Massimiliano Vari, Maria Stella Verrotti, Alberto Vigevano, Federico Vignoli, Aglaia Toonen, Ruud Zara, Federico Helbig, Ingo Striano, Pasquale Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title | Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title_full | Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title_fullStr | Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title_full_unstemmed | Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title_short | Epilepsy Course and Developmental Trajectories in STXBP1-DEE |
title_sort | epilepsy course and developmental trajectories in stxbp1-dee |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157582/ https://www.ncbi.nlm.nih.gov/pubmed/35655584 http://dx.doi.org/10.1212/NXG.0000000000000676 |
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