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Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

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dc.abstract.enObjective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. Significance: MAE is associated with significant neurodevelopmental impairment. MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorSimpson, Michael A.
dc.contributor.authorPal, Deb K.
dc.contributor.authorCraiu, Dana
dc.contributor.authorDavila, Carol
dc.contributor.authorTang, Shan
dc.contributor.authorObregia, Alexandru
dc.contributor.authorAddis, Laura
dc.contributor.authorJonghe, Peter De
dc.contributor.authorFallon, Penny
dc.contributor.authorWeckhuysen, Sarah
dc.contributor.authorRobinson, Robert
dc.contributor.authorCross, Helen J.
dc.contributor.authorHoffman-Zacharska, Dorota
dc.contributor.authorAbsoud, Michael
dc.contributor.authorMøller, Rikke S.
dc.contributor.authorHelbig, Ingo
dc.contributor.authorWeber, Yvonne G.
dc.contributor.authorSmith, Anna
dc.contributor.authorLehesjoki, Anna‐Elina
dc.contributor.authorTopp, Simon D.
dc.contributor.authorMuhle, Hiltrud
dc.contributor.authorPendziwiat, Manuela
dc.contributor.authorNeubauer, Bernd
dc.contributor.authorMei, Davide
dc.contributor.authorSelmer, Kaja
dc.contributor.authorParker, Alasdair
dc.contributor.authorAgrawal, Shakti
dc.contributor.authorCaglayan, Hande
dc.contributor.authorHedderly, Tammy
dc.contributor.authorEltze, Christin
dc.contributor.authorKerr, Tim
dc.contributor.authorDesurkar, Archana
dc.contributor.authorHussain, Nahin
dc.contributor.authorMarini, Carla
dc.contributor.authorGuerrini, Renzo
dc.contributor.authorStephani, Ulrich
dc.contributor.authorSterbova, Katalin
dc.contributor.authorHughes, Elaine
dc.contributor.authorStriano, Pasquale
dc.contributor.authorLascelles, Karine
dc.contributor.authorTalvik, Tiina
dc.contributor.authorWilliams, Ruth E.
dc.contributor.authorSpiczak, Sarah von
dc.contributor.authorKinali, Maria
dc.contributor.authorBagnasco, Irene
dc.contributor.authorVassallo, Grace
dc.contributor.authorWhitehouse, William
dc.contributor.authorGoyal, Sushma
dc.date.accessioned2024-01-25T16:36:06Z
dc.date.available2024-01-25T16:36:06Z
dc.date.copyright2020-05-29
dc.date.issued2020
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number5
dc.description.versionFINAL_PUBLISHED
dc.description.volume61
dc.identifier.doi10.1111/EPI.16508
dc.identifier.issn0013-9580
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/115801
dc.identifier.weblinkhttps://onlinelibrary.wiley.com/doi/10.1111/epi.16508
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofEpilepsia
dc.relation.pages995-1007
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enDoose syndrome
dc.subject.enepilepsy/seizures
dc.subject.engenetics
dc.subject.enmyoclonic astatic epilepsy
dc.titlePhenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures
dc.typeJournalArticle
dspace.entity.typePublication