Understanding relationships between autism, intelligence, and epilepsy: a cross‐disorder approach

Abstract

Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were filled out in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 4–63y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y range 4–22y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific for these conditions.

Early developmental pathways to autism spectrum disorder in tuberous sclerosis complex

“…Consistent with findings from older children with TSC showing associations between intellectual disability and ASD (Van Eeghen et al, 2013a), the results from this prospective study highlight the apparent inextricable link between cognitive development and ASD in TSC. On this basis, it has been suggested that cognitive impairment and social communicative deficits may stem from a common brain dysfunction in TSC (Van Eeghen et al, 2013a).…”

“…On this basis, it has been suggested that cognitive impairment and social communicative deficits may stem from a common brain dysfunction in TSC (Van Eeghen et al, 2013a). Findings from animal models of rare genetic disorders, including TSC, suggest that alterations in synaptic function and structure may be a possible common mechanism for the emergence of both ASD and ID (Zoghbi and Bear, 2012).…”

Epilepsy and Autism

“…In TSC, early seizure onset is associated with a high risk for ASD (Numis et al 2011;van Eeghen et al 2013). In a retrospective review of 103 patients with TSC, 40% were diagnosed with an ASD (Numis et al 2011).…”

Worries and needs of adults and parents of adults with neurofibromatosis type 1

“…Attention‐deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and sleep disturbance are also highly prevalent (Hyman et al, 2006; Leschziner et al, 2013; Morris et al, 2016) and can persist throughout life (Constantino et al, 2015; Descheemaeker et al, 2013; Mautner et al, 2015; van Eeghen AM et al, 2013). Furthermore, patients with NF1 are at risk for psychosocial problems.…”