PROJECT SUMMARY/ABSTRACT Atypical social communication is a core feature of ASD, with delayed or abnormal language constituting the most common initial cause for parental concern for children who are ultimately diagnosed. Vocal development in particular is often delayed or atypical in children with ASD, and growing literature suggests that as early as infancy, vocalization features such as volubility, vocal maturity, duration, and pitch may be useful in predicting later ASD diagnosis. However, little is known about the developmental processes and genetic mechanisms that contribute to these associations, limiting translational efforts to efficiently detect and treat abnormal development related to ASD and language delays. Characterizing early vocalization features in populations with neurogenetic syndromes (NGS) that are highly associated with ASD can address this gap, as NGS offer a “saturated” model for prospective surveillance of ASD emergence. Specifically, because the genetic abnormalities in NGS are already known, isolating phenotypic features that are specific to an NGS from features broadly shared across multiple NGS (e.g. features driven by shared intellectual or medical features) may inform biological contributors to ASD-associated atypical social communication. The present proposal uses this cross-syndrome approach to characterize early vocalization features and associations with ASD in 3 distinct, understudied NGS: Angelman syndrome (AS), Down syndrome (DS), and fragile X syndrome (FXS). Aim 1 will apply a novel coding pipeline to efficiently identify syndrome-specific profiles of early vocal development that are not limited by traditional shortcomings of standardized assessment tools. Indeed, these standardized measures are often ineffective at capturing variability in children with NGS due, in part, to high levels of “floor effects” that limit score variability. Thus, the results of this aim are expected to advance the field by (1) developing procedures for measuring early vocal development that are more appropriate for use in NGS populations, and (2) building on very limited understanding of early vocal development in 3 rare NGS populations. Aim 2 will then test the associations of early vocal features with ASD-associated features in AS, DS and FXS, all of which demonstrate unique etiological risk for developing ASD. Results of this aim are expected to improve our understanding of developmental and genetic pathways by which atypical social communication features are associated with ASD, as vocalization features that demonstrate associations with ASD features across multiple NGS groups can be considered robust predictors of ASD across etiologically-distinct risk groups, while syndrome-specific associations may inform distinct developmental or genetic mechanisms that may explain these associations. Overall, this project directly aligns with the mission of NIDCD to inform the developmental phenotypes and potential genetic bases of lang...