TY - JOUR
T1 - Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?
AU - Amiet, Claire
AU - Gourfinkel-An, Isabelle
AU - Laurent, Claudine
AU - Bodeau, Nicolas
AU - Génin, Bérengère
AU - Leguern, Eric
AU - Tordjman, Sylvie
AU - Cohen, David
N1 - Funding Information:
We gratefully acknowledge the resources provided by the AGRE Consortium and the participating AGRE families. The AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M Lajonchere (principal investigator). This work was supported by the Orange Foundation. The AGRE Consortium comprises: Dan Geschwind MD PhD UCLA, Los Angeles, CA, USA; Maja Bucan PhD, University of Pennsylvania, Philadelphia, PA, USA; W Ted Brown MD PhD FACMG, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; Rita M Cantor PhD, UCLA School of Medicine, Los Angeles, CA, USA; John N Constantino MD, Washington University School of Medicine, St Louis, MO, USA; T Conrad Gilliam PhD, University of Chicago, Chicago, IL, USA; Martha Herbert MD PhD, University of Texas, Houston, TX, USA; Clara Lajonchere PhD, Cure Autism Now, Los Angeles, CA, USA; David H Ledbetter PhD, Emory University, Atlanta, GA, USA; Christa Lese-Martin PhD, Emory University, Atlanta, GA, USA; Janet Miller, JD, PhD, Cure Autism Now, Los Angeles, CA, USA; Stanley F Nelson MD, UCLA School of Medicine, Los Angeles, CA, USA; Gerard D Schellenberg PhD, University of Washington, Seattle, WA, USA; Carol A Samango-Sprouse EdD, George Washington University, Washington, DC, USA; Sarah Spence MD PhD, Harvard University, Boston, MA, USA; Matthew State MD PhD, Yale University, New Haven, CT, USA; Rudolph E Tanzi PhD, Massachusetts General Hospital, Boston, MA, USA.
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
KW - Autism
KW - Epilepsy
KW - Intellectual disability
KW - Multiplex pedigree
UR - http://www.scopus.com/inward/record.url?scp=84888350760&partnerID=8YFLogxK
U2 - 10.1186/2040-2392-4-47
DO - 10.1186/2040-2392-4-47
M3 - Article
AN - SCOPUS:84888350760
SN - 2040-2392
VL - 4
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 47
ER -