Fragile X syndrome, an X-linked disorder that is more common in males than females, is the leading inherited cause of intellectual disability and the most common single-gene cause of autism spectrum disorder (ASD), with as many as 90% of males with FXS demonstrating at least some ASD symptomatology and up to 60% of males warranting a comorbid diagnosis of ASD. The combined presence of intellectual disability, social anxiety, ASD symptomatology, and heighted risk for attentional/inhibitory control difficulties place individuals with FXS at risk for language problems. However, evidence suggests that, despite having delays in language relative to age, males with FXS are more efficient word learners than are males with nonsyndromic ASD of comparable developmental levels. This finding is surprising given that the former display more severe cognitive impairments and higher rates of anxiety and hyperactivity, characteristics likely to impede the word learning process. Moreover, differences in ASD severity do not appear to fully explain this FXS lexical advantage. We hypothesize that this lexical difference is, in part, related to the fact that some of the foundational skills supporting lexical development are less impaired in children with FXS than in nonsyndromic ASD, even when matched on ASD severity. We also hypothesize that ASD symptomatology in individuals with FXS masks an interest in social interaction that distinguishes them from individuals with nonsyndromic ASD and facilitates early word learning. In the proposed project, we will examine lexical development in 3- to 6-year-olds with FXS or nonsyndromic ASD, with a focus on the foundational skills supporting lexical development and on the challenging behaviors that may serve as barriers to lexical development. In addition, direct comparisons will be made to (1) provide a downward extension (in terms of age) of previous findings that males with FXS achieve better vocabularies than do IQ-matched males with nonsyndromic ASD and (2) elucidate the factors underlying lexical development in these two conditions. Such in-depth analyses of the similarities and differences between FXS and nonsyndromic ASD will inform our understanding of the neurocognitive mechanisms underlying their phenotypes and advance models of lexical development in typically developing children. In addition, this direct comparison of the developmental trajectories of these two disorders is needed to (1) develop optimal treatment approaches and (2) verify the claim that, because of their shared symptomatology, targeted treatments benefitting FXS will be equally beneficial for ASD.
The proposed project is of high public health significance as it will provide important insights into the behavioral phenotype of fragile X syndrome, the leading inherited cause of intellectual disability and the most common single-gene cause of autism spectrum disorder. The project is focused on understanding lexical development in children with fragile X syndrome or autism spectrum disorder. The proposed project also seeks to clarify when the same or different treatment approaches should be used in fragile X syndrome and autism spectrum disorder by deciphering the extent to which lexical achievement in these conditions results from the same or different underlying mechanisms, which is relevant to the mission of NIDCD and NIH as a whole.
