COGNITIVE PROFILES OF CHILDREN WITH ARID1B-RELATED DISORDER: PRELIMINARY FINDINGS FROM THE MULTICENTER NATURAL HISTORY STUDY

Background: ARID1B-related disorder (ARID1B-RD) is a monogenic cause of neurodevelopmental disorders (estimated prevalence ~1 in 9,500 [1]), characterized by intellectual disability, developmental delay and a high incidence of autism spectrum disorder. Cognitive profiling and longitudinal natural history data are limited. We aimed to delineate cognitive profiles in children with ARID1B-RD using standardized baseline assessments within a prospective, longitudinal, multicenter study.
Methods: The first 10 children (aged 2-18 years) recruited in Turkey with pathogenic/likely pathogenic ARID1B variants underwent evaluation, including the Leiter International Performance Scale-3 (Leiter-3) for nonverbal cognitive ability, the Peabody Picture Vocabulary Test (PPVT-4) for receptive language, and the Vineland Adaptive Behavior Scales (Vineland-3) for adaptive functioning. These assessments are part of a 36-month natural history study conducted across multiple international sites. The broader study aims to enroll 100 children from six international centers to characterize the natural history of ARID1B-RD.
Results: Baseline data from the first 5 participants reveal a mean nonverbal IQ of 83.25 (range: 71-110) as assessed by Leiter-3, indicating a broad spectrum of cognitive impairments, reflecting intellectual functioning that is below average. PPVT-4 scores were low for age (mean standard score: 40; range: 20–84), spanning moderate to extremely severe delays. Vineland-3 indicated below-average adaptive functioning (mean standard score: 82; range: 67–99) with deficits in communication, daily living skills, and socialization, highlighting heterogeneity in ARID1B-RD.
Conclusions: Children with ARID1B-RD show substantial and heterogeneous cognitive, language, and adaptive challenges at baseline. Longitudinal follow-up in the full cohort will clarify developmental trajectories and inform targeted interventions.