Openly accessible

Phenotypic analysis of 303 multiplex families with common epilepsies

Epi4K Consortium, Abou-Khalil, Bassel, Afawi, Zaid, Allen, Andrew S., Bautista, Jocelyn F., Bellows, Susannah T., Berkovic, Samuel F., Bluvstein, Judith, Burgess, Rosemary, Cascino, Gregory, Cops, Elisa J., Cossette, Patrick, Crompton, Douglas E., Delanty, Norman, Devinsky, Orrin, Dluglos, Dennis, Epstein, Michael P., Fountain, Nathan B., Freyer, Catharine, Garry, Sarah I. and Winawer, MR 2017, Phenotypic analysis of 303 multiplex families with common epilepsies, Brain, vol. 140, no. 8, pp. 2144-2156, doi: 10.1093/brain/awx129.

Attached Files
Name Description MIMEType Size Downloads

Title Phenotypic analysis of 303 multiplex families with common epilepsies
Author(s) Epi4K Consortium
Abou-Khalil, Bassel
Afawi, Zaid
Allen, Andrew S.
Bautista, Jocelyn F.
Bellows, Susannah T.
Berkovic, Samuel F.
Bluvstein, Judith
Burgess, Rosemary
Cascino, Gregory
Cops, Elisa J.
Cossette, Patrick
Crompton, Douglas E.
Delanty, Norman
Devinsky, Orrin
Dluglos, Dennis
Epstein, Michael P.
Fountain, Nathan B.
Freyer, Catharine
Garry, Sarah I.
Winawer, MR
Journal name Brain
Volume number 140
Issue number 8
Start page 2144
End page 2156
Total pages 13
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2017-08
ISSN 1460-2156
Keyword(s) epilepsy
multiplex families
Age of Onset
Child, Preschool
Epilepsy, Generalized
Family Health
Sex Factors
Young Adult
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
Febrile seizures plus
Idiopathic generalized epilepsy
Benign childhood epilepsy
Glucose-transporter glut1
Severe myoclonic epilepsy
temporal lobe epilepsy
Rolandic epilepsy
Centrotemporal spikes
Absence epilepsy
Genetic epilepsty
Summary Gene identification in epilepsy has mainly been limited to large families segregating genes of major effect and de novo mutations in epileptic encephalopathies. Many families that present with common non-acquired focal epilepsies and genetic generalized epilepsies remain unexplained. We assembled a cohort of 'genetically enriched' common epilepsies by collecting and phenotyping families containing multiple individuals with unprovoked seizures. We aimed to determine if specific clinical epilepsy features aggregate within families, and whether this segregation of phenotypes may constitute distinct 'familial syndromes' that could inform genomic analyses. Families with three or more individuals with unprovoked seizures were studied across multiple international centres. Affected individuals were phenotyped and classified according to specific electroclinical syndromes. Families were categorized based on syndromic groupings of affected family members, examined for pedigree structure and phenotypic patterns and, where possible, assigned specific familial epilepsy syndromes. A total of 303 families were assembled and analysed, comprising 1120 affected phenotyped individuals. Of the 303 families, 117 exclusively segregated generalized epilepsy, 62 focal epilepsy, and 22 were classified as genetic epilepsy with febrile seizures plus. Over one-third (102 families) were observed to have mixed epilepsy phenotypes: 78 had both generalized and focal epilepsy features within the same individual (n = 39), or within first or second degree relatives (n = 39). Among the genetic generalized epilepsy families, absence epilepsies were found to cluster within families independently of juvenile myoclonic epilepsy, and significantly more females were affected than males. Of the 62 familial focal epilepsy families, two previously undescribed familial focal syndrome patterns were evident: 15 families had posterior quadrant epilepsies, including seven with occipito-temporal localization and seven with temporo-parietal foci, and four families displayed familial focal epilepsy of childhood with multiple affected siblings that was suggestive of recessive inheritance. The findings suggest (i) specific patterns of syndromic familial aggregation occur, including newly recognized forms of familial focal epilepsy; (ii) although syndrome-specificity usually occurs in multiplex families, the one-third of families with features of both focal and generalized epilepsy is suggestive of shared genetic determinants; and (iii) patterns of features observed across families including pedigree structure, sex, and age of onset may hold clues for future gene identification. Such detailed phenotypic information will be invaluable in the conditioning and interpretation of forthcoming sequencing data to understand the genetic architecture and inter-relationships of the common epilepsy syndromes.
Language eng
DOI 10.1093/brain/awx129
Field of Research 110399 Clinical Sciences not elsewhere classified
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, The Author
Free to Read? Yes
Persistent URL

Document type: Journal Article
Collections: Faculty of Health
School of Psychology
Open Access Collection
Connect to link resolver
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in TR Web of Science
Scopus Citation Count Cited 18 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 281 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Mon, 28 May 2018, 01:01:05 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact