Skip to main content

Research Repository

Advanced Search

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

Tang, Shan; Addis, Laura; Smith, Anna; Topp, Simon D.; Pendziwiat, Manuela; Mei, Davide; Parker, Alasdair; Agrawal, Shakti; Hughes, Elaine; Lascelles, Karine; Williams, Ruth E.; Fallon, Penny; Robinson, Robert; Cross, Helen J.; Hedderly, Tammy; Eltze, Christin; Kerr, Tim; Desurkar, Archana; Hussain, Nahin; Kinali, Maria; Bagnasco, Irene; Vassallo, Grace; Whitehouse, William; Goyal, Sushma; Absoud, Michael; EuroEPINOMICS?RES Consortium; M�ller, Rikke S.; Helbig, Ingo; Weber, Yvonne G.; Marini, Carla; Guerrini, Renzo; Simpson, Michael A.; Pal, Deb K.

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures Thumbnail


Authors

Shan Tang

Laura Addis

Anna Smith

Simon D. Topp

Manuela Pendziwiat

Davide Mei

Alasdair Parker

Shakti Agrawal

Elaine Hughes

Karine Lascelles

Ruth E. Williams

Penny Fallon

Robert Robinson

Helen J. Cross

Tammy Hedderly

Christin Eltze

Tim Kerr

Archana Desurkar

Nahin Hussain

Maria Kinali

Irene Bagnasco

Grace Vassallo

William Whitehouse

Sushma Goyal

Michael Absoud

EuroEPINOMICS?RES Consortium

Rikke S. M�ller

Ingo Helbig

Yvonne G. Weber

Carla Marini

Renzo Guerrini

Michael A. Simpson

Deb K. Pal



Abstract

Objective: 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.

Citation

Tang, S., Addis, L., Smith, A., Topp, S. D., Pendziwiat, M., Mei, D., …Pal, D. K. (2020). Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia, 61(5), 995-1007. https://doi.org/10.1111/epi.16508

Journal Article Type Article
Acceptance Date Mar 27, 2020
Online Publication Date May 29, 2020
Publication Date May 29, 2020
Deposit Date Jun 16, 2020
Publicly Available Date Mar 28, 2024
Journal Epilepsia
Print ISSN 0013-9580
Electronic ISSN 1528-1167
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 61
Issue 5
Pages 995-1007
DOI https://doi.org/10.1111/epi.16508
Keywords Doose syndrome, epilepsy/seizures, genetics, myoclonic astatic epilepsy
Public URL https://nottingham-repository.worktribe.com/output/4661060
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16508?af=R
Additional Information Tang, S., Addis, L., Smith, A., Topp, S. D., Pendziwiat, M., … Mei, D. (2020). Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia, 61(5), 995–1007. https://doi.org/10.1111/epi.16508

Files




You might also like



Downloadable Citations