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Open Access Research

Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?

Claire Amiet12, Isabelle Gourfinkel-An34, Claudine Laurent15, Nicolas Bodeau1, Bérengère Génin2, Eric Leguern34, Sylvie Tordjman6 and David Cohen17*

Author Affiliations

1 Department of Child and Adolescent Psychiatry, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Université Pierre et Marie Curie, 47 bd de l’Hôpital, 75013 Paris, France

2 IntegraGen, 5 rue Henri Desbruères, 91000 Évry, France

3 Center of Epileptology, Reference Center for Rare Epilepsies, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 47 bd de l’Hôpital, 75013 Paris, France

4 Department of Genetics, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Université Pierre et Marie Curie, 47 bd de l’Hôpital, 75013 Paris, France

5 Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CR-ICM), Université Pierre et Marie Curie/Institut national de la santé et de la recherche médicale (INSERM) Unité Mixte de Recherche (UMR) S975/Centre National de la Recherche Scientifique (CNRS) UMR 7225, Département Biotechnologies et Biothérapies, Groupe Hospitalier Pitié-Salpêtrière, 47 bd de l’Hôpital, 75013 Paris, France

6 Department of Child and Adolescent Psychiatry, Groupe Hospitalier Guillaume Régnier, Université de Rennes, 108 Avenue Du General Leclerc, 35703 Rennes, France

7 Institut des Systèmes Intelligents et Robotiques (ISIR), CNRS UMR 7222, Université Pierre et Marie Curie, 1 place Jussieu, 75005 Paris, France

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Molecular Autism 2013, 4:47  doi:10.1186/2040-2392-4-47

Published: 1 December 2013

Abstract

Background

Autism spectrum disorders (ASD) and epilepsy frequently occur together. Prevalence rates are variable, and have been attributed to age, gender, comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors. Recent studies have suggested disparate clinical and genetic settings depending on simplex or multiplex autism. The aim of this study was to assess: 1) the prevalence of epilepsy in multiplex autism and its association with genetic and non-genetic risk factors of major effect, intellectual disability and gender; and 2) whether autism and epilepsy cosegregate within multiplex autism families.

Methods

We extracted from the Autism Genetic Resource Exchange (AGRE) database (n = 3,818 children from 1,264 families) all families with relevant medical data (n = 664 children from 290 families). The sample included 478 children with ASD and 186 siblings without ASD. We analyzed the following variables: seizures, genetic and non-genetic risk factors, gender, and cognitive functioning as assessed by Raven’s Colored Progressive Matrices (RCPM) and Vineland Adaptive Behavior Scales (VABS).

Results

The prevalence of epilepsy was 12.8% in cases with ASD and 2.2% in siblings without ASD (P <10-5). With each RCPM or VABS measure, the risk of epilepsy in multiplex autism was significantly associated with intellectual disability, but not with gender. Identified risk factors (genetic or non-genetic) of autism tended to be significantly associated with epilepsy (P = 0.052). When children with prematurity, pre- or perinatal insult, or cerebral palsy were excluded, a genetic risk factor was reported for 6/59 (10.2%) of children with epilepsy and 12/395 (3.0%) of children without epilepsy (P = 0.002). Finally, using a permutation test, there was significant evidence that the epilepsy phenotype co-segregated within families (P <10-4).

Conclusions

Epilepsy in multiplex autism may define a different subgroup in terms of clinical characteristics and genetic risk.

Keywords:
Autism; Multiplex pedigree; Epilepsy; Intellectual disability