Behavior in Phelan-McDermid Syndrome: Clinical Characteristics, Genetic and Metabolic Contributions, and Evaluation of Behavioral Assessment Tools

Phelan-McDermid syndrome (PMS) is characterized by genetic and phenotypic variability with varying levels of developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), speech delay, minor dysmorphic features, and behavioral issues. Genetic causes of PMS involve deletions in the 22q13.3 region or pathogenic/likely pathogenic variants in SHANK3. Due to the significant heterogeneity and complexities seen in individuals with PMS, there are numerous challenges surrounding research, accurate diagnoses, assessments, and the creation of treatments. Behavioral issues are present in the majority of individuals with PMS, including lower levels of adaptive behavioral skills needed for daily functioning, disruptive behaviors, restricted and repetitive behaviors (RRBs), and other behaviors often associated with ASD. Due to the complex nature of behavior in individuals with PMS and the challenges of assessing behavior in individuals with varying levels of ID and language abilities, a deeper characterization of behavior and assessment tools targeted to the neurodevelopmental disorder population is needed. This dissertation sought to integrate the framework of deep phenotyping to design three projects to address these gaps mentioned above in PMS research by working toward a deeper understanding of behavioral profiles in ID and PMS, analyzing genetic and metabolic contributors to behavior in PMS, and suggesting the best routes to clinically assessing behavior in individuals with PMS.