Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis.

Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.

Variability in Autism Symptom Trajectories Using Repeated Observations From 14 to 36 Months of Age.

OBJECTIVE: This study examined variability in autism symptom trajectories in toddlers referred for possible autism spectrum disorder (ASD) who had frequent observations from 14 to 36 months of age. METHOD: In total, 912 observations of the Autism Diagnostic Observation Schedule (ADOS) were obtained from 149 children (103 with ASD) followed from 14 to 36 months of age. As a follow-up to a previous analysis of ADOS algorithm scores, a different analytic approach (Proc Traj) was implemented to identify several courses of symptom trajectories using ADOS Calibrated Severity Scores in a larger sample. Proc Traj is a statistical method that clusters individuals into separate groups based on different growth trajectories. Changes in symptom severity based on individual ADOS items also were examined. RESULTS: Trajectory analysis of overall symptom severity identified 4 clusters (non-spectrum ∼25%; worsening ∼27%; moderately-improving ∼25%; severe-persistent ∼23%). Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, level of baseline and final verbal and nonverbal abilities, and symptom severity. For the moderately-improving group, social communication improved, whereas restricted and repetitive behaviors were stable over time. Language and verbal and nonverbal communication improved for many children, but several social affect and restricted and repetitive behavior symptoms remained stable or worsened. CONCLUSION: Significant variability in symptom trajectories was observed among toddlers referred for possible ASD. Changes in social and restricted and repetitive behavior domain scores did not always co-occur. Similarly, item-level trajectories did not always align with trajectories of overall severity scores. These findings highlight the importance of monitoring individual symptoms within broader symptom domains when conducting repeated assessments for young children with suspected ASD.

Stimulus processing and error monitoring in more-able kindergarteners with autism spectrum disorder: a short review and a preliminary Event-Related Potentials study.

Deficits in executive functions (EF) in individuals with autism spectrum disorder (ASD) have been identified. However, there is limited evidence about patterns of deficits in EF-related skills, especially at the neurobiological level, in young children with ASD and little is known about how these skills are related to other domains of functioning and symptom severity. In this study, we provide a focused review of EF-related Event-Related Potentials (ERP) studies in children with ASD, accompanied by preliminary data for neurophysiological correlates of EF on a child-friendly Go/No-go task. We focus our preliminary investigation on ERPs associated with stimulus processing (N2, P3) and error monitoring [error/correct-related negativity (ERN, CRN), error positivity (Pe)] in 5-year-old kindergarteners with ASD and typical controls matched on age, gender and task accuracy. Children with ASD showed significantly greater amplitudes of ERN/CRN compared to matched controls, suggesting heightened response monitoring. The ASD group also showed less distinct inhibitory P3 compared to the TD group, potentially suggesting atypical stimulus processing. In children with ASD, higher autism symptom severity was correlated with larger P3. Better behavioral performance on an EF-related task was correlated with smaller CRN. Our study is the first investigation to demonstrate the presence of N2, P3, ERN/CRN and Pe in kindergartners with ASD. The potential links between ERP patterns and behavioral and clinical features in more-able children with ASD highlight the need for further exploration into the functional mechanisms of these atypical neural activities and for more focused behavioral interventions targeting cognitive control and response monitoring.