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Background  Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms.    Methods  Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization.    Results  Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC.    Conclusions  These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments.

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study