Differential Cognitive and Behavioral Development from 6 to 24 Months in Autism and Fragile X Syndrome

Abstract Background: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies but similar clinical phenotypes is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history (FH) of autism spectrum disorder (ASD) who go on to develop autism themselves (FH-ASD), including differences in brain development and behavioral symptomology. However, there have been no studies investigating differential developmental skill profiles in FXS and FH-ASD infants. Methods: The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in infants with FXS and FH-ASD infants, compared to typically developing controls and FH infants who did not develop ASD (FH-nonASD). Results: Infants with FXS showed delays in developmental composite scores compared to FH-ASD (and FH-nonASD and control) infants as early as 6 months of age. At 12 months an ordinal pattern was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Conclusions: Our results demonstrate detectable delays by 6 months in FXS, whereas FH-ASD infants were indistinguishable from typically developing infants until 12 months. This highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more subtly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD add to our understanding of important distinctions in the development and behavioral phenotype of these two groups.