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

被引：35

作者：

Amiet, Claire ^{[1
,2
]}

Gourfinkel-An, Isabelle ^{[3
,4
]}

Laurent, Claudine ^{[1
,5
]}

Bodeau, Nicolas ^{[1
]}

Genin, Berengere ^{[2
]}

Leguern, Eric ^{[3
,4
]}

Tordjman, Sylvie ^{[6
]}

Cohen, David ^{[1
,7
]}

机构：

[1] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Dept Child & Adolescent Psychiat, F-75013 Paris, France

[2] IntegraGen, F-91000 Evry, France

[3] Grp Hosp Pitie Salpetriere, AP HP, Reference Ctr Rare Epilepsies, Ctr Epileptol, F-75013 Paris, France

[4] Univ Paris 06, AP HP, Grp Hosp Pitie Salpetriere, Dept Genet, F-75013 Paris, France

[5] Univ Paris 06, INSERM, CR ICM,Grp Hosp Pitie Salpetriere, UMR S975,CNRS,UMR 7225,Dept Biotechnol & Biothera, F-75013 Paris, France

[6] Univ Rennes, Grp Hosp Guillaume Regnier, Dept Child & Adolescent Psychiat, F-35703 Rennes, France

[7] Univ Paris 06, CNRS, ISIR, UMR 7222, F-75005 Paris, France

来源：

MOLECULAR AUTISM | 2013年 / 4卷

关键词：

Autism; Multiplex pedigree; Epilepsy; Intellectual disability; 3Q29 MICRODELETION SYNDROME; DE-NOVO MUTATIONS; SCAFFOLDING PROTEIN SHANK3; LINKED MENTAL-RETARDATION; SEVERE MYOCLONIC EPILEPSY; POTASSIUM CHANNEL GENE; COPY NUMBER VARIANTS; SPECTRUM DISORDERS; SODIUM-CHANNEL; INFANTILE SPASMS;

D O I：

10.1186/2040-2392-4-47

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：16

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