Thus, we sought to explore the neuro‐phenotypic “landscape” of FXS to attempt to determine whether there may be previously undiscovered biological underpinnings to this behavioral observation. Our motivation to search for neuro‐phenotypic subgroups within FXS derived from previous studies suggesting the existence of behavioral subgroups based on whether individuals met criteria for autism. that suggests methylation status may constitute a biomarker for predicting response to AFQ056, a subtype‐selective mGluR5 inhibitor. To date, there has been little work suggesting the existence of separable neurobiological phenotypes within FXS, the notable exception being a study by Jacquemont et al. In the study presented here, we concentrate exclusively on children with FXS in order to explore the degree to which neurobiological heterogeneity may be present within the FXS population itself. This finding also supports the hypothesis that there is a high level of neurobiological heterogeneity among individuals meeting diagnostic criteria for iASD. These differences were of sufficient magnitude that the two populations could be discriminated with a high degree of accuracy (90%) through the use of machine learning approaches. A recent study by our group however, showed that the gray and white matter profiles of young children with FXS are significantly different from those of children with idiopathic autism (iAUT i.e., who do not have FXS). © 2014 Wiley Periodicals, Inc.īecause of similarities between the behavioral profiles of children with the single gene disorder fragile X syndrome (FXS) and the criteria used to define autism spectrum disorders (ASD), it had been hoped that FXS might serve as a useful genetically‐defined model for studying ASD. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. Comparison of these subgroups showed significant between‐subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e.g., enlarged caudate). Application of topological methods to structural MRI data revealed two large subgroups within the study population. To this end, we analyzed imaging and behavioral data from young boys ( n = 52 aged 1.57–4.15 years) diagnosed with FXS. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism‐related behaviors. Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single‐gene risk factor for autism.
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