Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/92758
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Type: Journal article
Title: Genetics of epilepsy: the testimony of twins in the molecular era
Author: Vadlamudi, L.
Milne, R.
Lawrence, K.
Heron, S.
Eckhaus, J.
Keay, D.
Connellan, M.
Torn-Broers, Y.
Howell, R.
Mulley, J.
Scheffer, I.
Dibbens, L.
Hopper, J.
Berkovic, S.
Citation: Neurology, 2014; 83(12):1042-1048
Publisher: American Academy of Neurology
Issue Date: 2014
ISSN: 0028-3878
1526-632X
Statement of
Responsibility: 
Lata Vadlamudi, Roger L. Milne, Kate Lawrence, Sarah E. Heron, Jazmin Eckhaus, Deborah Keay, Mary Connellan, Yvonne Torn-Broers, R. Anne Howell, John C. Mulley, Ingrid E. Scheffer, Leanne M. Dibbens, John L. Hopper and Samuel F. Berkovic
Abstract: OBJECTIVE: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses. METHODS: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes. Epilepsies were then grouped according to the 2010 ILAE organizational scheme. Molecular genetic information was utilized where applicable. RESULTS: Of 558 twin pairs, 418 had confirmed seizures. A total of 534 twin individuals were affected. There were higher twin concordance estimates for monozygotic (MZ) than for dizygotic (DZ) twins for idiopathic generalized epilepsies (MZ = 0.77; DZ = 0.35), genetic epilepsy with febrile seizures plus (MZ = 0.85; DZ = 0.25), and focal epilepsies (MZ = 0.40; DZ = 0.03). Utilizing the 2010 ILAE scheme, the twin data clearly demonstrated genetic influences in the syndromes designated as genetic. Of the 384 tested twin individuals, 10.9% had mutations of large effect in known epilepsy genes or carried validated susceptibility alleles. CONCLUSIONS: Twin studies confirm clear genetic influences for specific epilepsies. Analysis of the twin sample using the 2010 ILAE scheme strongly supported the validity of grouping the "genetic" syndromes together and shows this organizational scheme to be a more flexible and biologically meaningful system than previous classifications. Successful selected molecular testing applied to this cohort is the prelude to future large-scale next-generation sequencing of epilepsy research cohorts. Insights into genetic architecture provided by twin studies provide essential data for optimizing such approaches.
Keywords: Epilepsies, Partial; Epilepsy, Generalized; Cohort Studies; Twins, Dizygotic; Twins, Monozygotic; Seizures, Febrile; Genetic Predisposition to Disease
Rights: © 2014 American Academy of Neurology
RMID: 0030028149
DOI: 10.1212/WNL.0000000000000790
Grant ID: http://purl.org/au-research/grants/nhmrc/628911
http://purl.org/au-research/grants/nhmrc/400121
http://purl.org/au-research/grants/nhmrc/628952
Appears in Collections:Paediatrics publications

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