Abstract
BackgroundTargeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) have been studied as a model for this approach, and important areas of phenotypic overlap and divergence have been documented. However, few studies have examined how the manifestation of ASD-related phenotypes in FXS may change over development, a question which has important implications for conceptualizing shared etiologies of these disorders and their constituent phenotypes. The goal of this study was to characterize ASD phenotypes in boys and girls with FXS across development, as well as to compare individual component phenotypes among boys with FXS and boys with idiopathic ASD (ASD-O) over time.MethodsSixty-five boys and girls with FXS and 19 boys with ASD-O completed a battery of diagnostic, cognitive, and language assessments at two time points (mean 2.5 years apart). Nonparametric tests assessed changes in diagnostic classification in FXS over time, and hierarchical linear modeling and repeated measures assessed changes in individual ASD symptoms in FXS over time. Additionally, ANCOVAs compared ASD symptom severity and component phenotypes in boys with FXS-O, FXS-ASD, and ASD-O at both time points.ResultsOverall, ASD symptom manifestation for children with FXS significantly increased over time, and developmental predictors varied based on the domain of symptoms assessed. The greatest degree of overlap was observed between boys with FXS-ASD and ASD-O in the domain of reciprocal social communication across time points, whereas boys with ASD-O demonstrated greater impairment in restricted and repetitive behaviors at the later time point.ConclusionsASD symptoms increased in FXS with age, and social language impairment emerged as a potential core shared feature of FXS and ASD that may help elucidate underlying molecular genetic variation related to phenotypic variance, and aid intervention planning for subgroups of children showing distinct phenotypes. Results highlight the value of a developmental perspective, and longitudinal data in particular, in evaluating shared behavioral phenotypes across genetic conditions, lending insight into underlying cognitive, neural, and genetic mechanisms associated with key developmental phenotypes in ASD and FXS.
Highlights
Targeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships
This paper examines developmental changes in diagnostic classification, symptom expression, and related abilities in fragile X syndrome (FXS) and autism spectrum disorder (ASD), two complex neurodevelopmental disorders with considerable phenotypic overlap
This study examined the developmental manifestation of ASD phenotypes in Fragile X syndrome (FXS), drawing from comprehensive longitudinal assessments of children with FXS and idiopathic ASD (i.e., ASD-O) using gold-standard ASD diagnostic measures, and standardized assessments of cognition, structural language, and pragmatic language
Summary
Targeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships. Longitudinal research on disorders such as attention deficit-hyperactivity disorder [52], Down syndrome [44], and autism spectrum disorder (ASD; [14, 62]) demonstrate changes in clinical symptoms and underlying neurobiology across the lifespan, underscoring the importance of examining development when characterizing symptomatology within and across different psychiatric disorders. This paper examines developmental changes in diagnostic classification, symptom expression, and related abilities in fragile X syndrome (FXS) and ASD, two complex neurodevelopmental disorders with considerable phenotypic overlap. At both behavioral and neurobiological levels, FXS and ASD are characterized by atypical developmental trajectories. Charting the dual paths of phenotypic development in each disorder can help to identify markers of shared etiology throughout the lifespan, with direct clinical, methodological, and theoretical implications
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