Developmental Trajectories in ARID1B-Related Disorder – a Multi-Method Multi-Site Prospective Natural History Study

ARID1B is the most frequently mutated single gene in neurodevelopmental disorders (NDDs) that are not inherited, with an approximated prevalence of one in 9,500 individuals. ARID1B-related disorder (ARID1B-RD) manifests in early childhood as moderate to severe developmental delay, and children and adults with the disorder have intellectual disability (ID) and are often diagnosed with autism spectrum disorder alongside many other clinical signs. Despite ARID1B RD’s high prevalence and extensive debilitating effects, the current understanding of how the disorder develops over time is strikingly limited. The proposed project will address this gap by employing a prospective longitudinal multi method design. Specifically, in seven sites, we will monitor the development of 135 children and adolescents aged 2-18 with ARID1B-RD for 30 months. Monitoring will involve (a) administration of standardized NDD assessments by clinicians complemented by caregivers’ reports; (b) evaluation of biological aspects of ARID1B-RD (for example, electric brain activity); and (c) collection daily life data via caregivers’ reports, and auditory and activity data using microphones and smartwatches. The project team brings a diverse set of complementary skills and collaborates with leading patient advocacy organizations. The project will generate a comprehensive picture of the progression of ARID1B-RD. The generated data will allow identifying and validating measurable targets for interventions, thus facilitating the development of effective treatments for thousands of children worldwide.

This project is an international collaborative effort, involving the following world-renowned Institutes: The Hebrew University of Jerusalem (Israel, coordinator), University of Montreal (Canada), Heinrich-Heine-University and Universitätsklinikum Bonn (Germany), University of Verona (Italy), Lyon University Hospital (France), Karolinska Institutet (Sweden), Acibadem Mehmet Ali Aydinlar Üniversitesi (Turkey).