Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy

Objectives: To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population. Methods: Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy. Results: The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001). Conclusion: This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy

Prevalence of Epilepsy by Age among Individuals with Autism Spectrum Disorder, All Studies.

<p>The percentage of children with epilepsy by age group by study sample. The prevalence is higher in older children than younger children. Abbreviations: AGRE, the Autism Genetic Resource Exchange; SSC, the Simons Simplex Collection; AC, the Autism Consortium; NSCH, 2007 the National Survey of Children’s Health.</p

Epilepsy Diagnosis by Gender and Age among Individuals with Autism Spectrum Disorder.

<p>Abbreviations: NSCH, 2007 National Survey of Children’s Health; Wt. %, weighted percentage; CI, confidence interval.</p>a<p>Genetic Collaborative Samples (AGRE, SSC, and AC) combined.</p>b<p>Unweighted number of children.</p

Summary of Samples and Measures.

<p>Abbreviations: ASD, Autism Spectrum Disorder; ADI-R, Autism Diagnostic Interview–Revised.</p

Logistic Regression Modeling the Odds of an Epilepsy Diagnosis by Demographic and Clinical Characteristics, Combined Genetic Collaborative Sample^a.

<p>Abbreviations: OR, odds ratio; CI, confidence interval; FSIQ, full scale IQ score.</p>a<p>Genetic Collaborative Samples (AGRE, SSC, and AC) combined.</p><p>Model 1: Individual models for each variable.</p><p>Model 2: Individual models for each variable, adjusted for full scale IQ score only.</p><p>Model 3: Single model adjusted for all variables.</p><p>Odds ratios for full scale IQ score and adaptive behavior composite score represent the odds of epilepsy for a one standard deviation increase.</p

Distribution of Epilepsy among Individuals with Autism Spectrum Disorder by Study Sample.

<p>Abbreviations: AGRE, the Autism Genetic Resource Exchange; SSC, the Simons Simplex Collection; AC, the Autism Consortium; NSCH, the 2007 National Survey of Children’s Health; Wt. %, weighted percentage; CI, confidence interval.</p>a<p>Genetic Collaborative Samples (AGRE, SSC, and AC) combined.</p>b<p>Unweighted number of children.</p

Intellectual Disability Is Associated with Increased Runs of Homozygosity in Simplex Autism

Intellectual disability (ID), often attributed to autosomal-recessive mutations, occurs in 40% of autism spectrum disorders (ASDs). For this reason, we conducted a genome-wide analysis of runs of homozygosity (ROH) in simplex ASD-affected families consisting of a proband diagnosed with ASD and at least one unaffected sibling. In these families, probands with an IQ ≤ 70 show more ROH than their unaffected siblings, whereas probands with an IQ &gt; 70 do not show this excess. Although ASD is far more common in males than in females, the proportion of females increases with decreasing IQ. Our data do support an association between ROH burden and autism diagnosis in girls; however, we are not able to show that this effect is independent of low IQ. We have also discovered several autism candidate genes on the basis of finding (1) a single gene that is within an ROH interval and that is recurrent in autism or (2) a gene that is within an autism ROH block and that harbors a homozygous, rare deleterious variant upon analysis of exome-sequencing data. In summary, our data suggest a distinct genetic architecture for participants with autism and co-occurring intellectual disability and that this architecture could involve a role for recessively inherited loci for this autism subgroup