Clinical Characterization of Epilepsy in Children With Angelman Syndrome.
15q11-13
Angelman syndrome
Epilepsy
GABA
GABR
Genotype
Seizures
UBE3A
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
29
05
2021
revised:
18
08
2021
accepted:
23
08
2021
pubmed:
19
9
2021
medline:
19
2
2022
entrez:
18
9
2021
Statut:
ppublish
Résumé
Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design. We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype. Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P < 0.001). Compared with participants with a nondeletion genotype, those with deletions were younger at the time of the first seizure (age: median [95% confidence interval]: 24 [21-24] months vs. 57 [36-85] months, P < 0.001) and had a higher prevalence of generalized motor seizures. Hospitalization following a seizure was reported in more children with a deletion than a nondeletion genotype (92 of 171 [54%] vs. 17 of 48 [36%], P = 0.04). The overall prevalence of absence seizures was not significantly different between genotype groups. Forty-six percent (102/219) of the individuals reporting epilepsy were diagnosed with AS concurrently or after their first seizure. Significant differences exist in the clinical expression of epilepsy in AS according to the underlying genotype, with earlier age of onset and more severe epilepsy in individuals with AS due to a chromosome 15 deletion.
Sections du résumé
BACKGROUND
Epilepsy is highly prevalent in children with Angelman syndrome (AS), and its detailed characterization and relationship to the genotype (deletion vs nondeletion) is important both for medical practice and for clinical trial design.
METHODS AND MATERIALS
We retrospectively analyzed the main clinical features of epilepsy in 265 children with AS who were enrolled in the AS Natural History Study, a multicenter, observational study conducted at six centers in the United States. Participants were prospectively followed up and classified by genotype.
RESULTS
Epilepsy was reported in a greater proportion of individuals with a deletion than a nondeletion genotype (171 of 187 [91%] vs. 48 of 78 [61%], P < 0.001). Compared with participants with a nondeletion genotype, those with deletions were younger at the time of the first seizure (age: median [95% confidence interval]: 24 [21-24] months vs. 57 [36-85] months, P < 0.001) and had a higher prevalence of generalized motor seizures. Hospitalization following a seizure was reported in more children with a deletion than a nondeletion genotype (92 of 171 [54%] vs. 17 of 48 [36%], P = 0.04). The overall prevalence of absence seizures was not significantly different between genotype groups. Forty-six percent (102/219) of the individuals reporting epilepsy were diagnosed with AS concurrently or after their first seizure.
CONCLUSIONS
Significant differences exist in the clinical expression of epilepsy in AS according to the underlying genotype, with earlier age of onset and more severe epilepsy in individuals with AS due to a chromosome 15 deletion.
Identifiants
pubmed: 34536900
pii: S0887-8994(21)00180-6
doi: 10.1016/j.pediatrneurol.2021.08.007
pmc: PMC8500934
mid: NIHMS1737103
pii:
doi:
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
42-50Subventions
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD061222
Pays : United States
Organisme : NCRR NIH HHS
ID : U54 RR019478
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
J Med Genet. 2001 Dec;38(12):834-45
pubmed: 11748306
Mol Psychiatry. 2021 Jul;26(7):3625-3633
pubmed: 32792659
Epilepsy Behav. 2016 Jul;60:138-141
pubmed: 27206232
Eur J Hum Genet. 2007 Sep;15(9):943-9
pubmed: 17522620
Epilepsia. 2018 Mar;59(3):523-529
pubmed: 29327337
Epilepsy Behav. 2018 Mar;80:346-353
pubmed: 29402631
Epilepsia. 2017 Apr;58(4):512-521
pubmed: 28276062
Arch Neurol. 2005 Mar;62(3):371-6
pubmed: 15767501
Am J Med Genet A. 2020 Jan;182(1):53-63
pubmed: 31729827
Am J Med Genet A. 2006 Mar 1;140(5):413-8
pubmed: 16470747
Eur J Med Genet. 2016 Jun;59(6-7):315-9
pubmed: 27174604
Epilepsy Behav. 2017 Oct;75:225-229
pubmed: 28827041
Genet Med. 2010 Jul;12(7):385-95
pubmed: 20445456
J Med Genet. 2003 Feb;40(2):87-95
pubmed: 12566516
Res Dev Disabil. 2016 Sep;56:177-82
pubmed: 27323320
Eur J Hum Genet. 1999 Feb-Mar;7(2):131-9
pubmed: 10196695
Pediatr Neurol. 2013 Apr;48(4):271-9
pubmed: 23498559
Patient. 2019 Feb;12(1):97-112
pubmed: 29987743
Am J Med Genet A. 2017 Mar;173(3):753-757
pubmed: 28211971
Eur J Hum Genet. 2004 Dec;12(12):987-92
pubmed: 15470370
Appl Clin Genet. 2014 May 16;7:93-104
pubmed: 24876791
Epilepsia. 2009 Nov;50(11):2369-76
pubmed: 19453717
Cochrane Database Syst Rev. 2017 Feb 14;2:CD003032
pubmed: 28195639
Child Psychiatry Hum Dev. 2021 Aug;52(4):654-668
pubmed: 32880036
Am J Med Genet A. 2013 Sep;161A(9):2197-203
pubmed: 23913711
Eur J Hum Genet. 2019 Nov;27(11):1649-1658
pubmed: 31186545
Biol Psychiatry. 2019 May 1;85(9):752-759
pubmed: 30826071
Am J Med Genet A. 2011 Jan;155A(1):81-90
pubmed: 21204213