Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype

Abstract

Objective: We aimed to assess a cohort of young patients with Dravet syndrome (DS) for intellectual disability (ID) and autism spectrum disorder (ASD) using standardized tools and parental questionnaires to delineate their specific profiles.

Methods: We included 35 patients with DS aged 24 months to 7 years, excluding patients with a developmental age (DA) <18 months (n = 5). We performed specific tests adapted for ID (Psychoeducational Profile, Third Edition [PEP-3]), in addition to the Child Development Inventory (CDI) and Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaires. We used 2 standardized tools for ASD: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). We compared the with parental questionnaires and the VABS-II, and with ASD characteristics.

Results: PEP-3 subscales showed pathologic development in all but one patient (97%): ID in 23 of 30 (77%), and borderline cognitive functioning in 6 of 30 (22%). Eleven patients (39%) had ASD and 2 (7%) had a Social Communication Disorder (SCD) diagnosis. We found no difference between PEP-3 and CDI categorization except for fine motor skills. We found significant negative correlations between ADOS-2 and PEP-3 for the majority of scores. For patients aged older than 50 months, 2 groups emerged (ASD/no ASD) with significant difference in DA. The logistic regression for ASD diagnosis explained by VABS-II showed a significant effect for Socialization, Motor Skills, and Adaptive Behavior.

Significance: We found a high prevalence of ID in patients with DS. ID is characterized by expressive and comprehensive communication deficits in addition to visuospatial difficulties. ASD showed a specific profile with a relative preservation of social skills, emphasizing a possible underdiagnosis. Parental questionnaires can provide a good assessment of cognitive profile and might allow the difficulty of addressing cognitive scales in DS to be overcome. The profile of ID and ASD should help to establish early adapted rehabilitation programs and emphasizes the global need for care beyond seizures in DS and other developmental epileptic encephalopathies.

Keywords: Parents’ questionnaires; autism spectrum disorder; cognitive scales; epileptic encephalopathy; intellectual disability.

Figure 1

Upper graph—proportion of patients for each developmental level of PEP‐3 scale according to the subscales. CVPV, Cognitive Verbal/Preverbal; EL, Expressive Language; RL, Receptive Language; FM, Fine Motor; GM, Gross Motor; VMI, Visual Motor Imitation; AE, Affective Expression; SR, Social Reciprocity; CMB, Characteristic Motor Behaviors; CVB, Characteristic Verbal Behaviors. Lower graph: Proportion of patients for each developmental level of the CDI scale according to the subscales. Soc, Social; SH, Self Help; GM, Gross Motor; FM, Fine Motor; EL, Expressive Language; LC, Language Comprehension; Let, Letters; Num, Numbers; GS, General Scale

Figure 2

Nonparametric density plot of bivariate analyses of the variables “PEP‐3 Receptive Language” and “CDI General Scale” with respect to Age (M = months)

Figure 3

Flow chart for diagnosis of autism spectrum disorder

Figure 4

Comparison of ADI‐R 3 subscores between Dravet syndrome (DS) children with autism spectrum disorder (ASD; in red) and DS children without ASD (in blue)