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Fragile X syndrome is a genetic condition associated with alterations in brain and subsequent cognitive development. However, due to a milder phenotype relative to males, females with fragile X syndrome are underrepresented in research studies. In the current study, we investigate neuroanatomical differences in young females (age range: 6.03–16.32 years) with fragile X syndrome ( N  = 46) as compared to age-, sex-, and verbal abilities-matched participants (comparison group;  N  = 35). Between-group analyses of whole-brain and regional brain volumes were assessed using voxel-based morphometry. Results demonstrate significantly larger total gray and white matter volumes in girls with fragile X syndrome compared to a matched comparison group ( P s &lt; 0.001). In addition, the fragile X group showed significantly larger gray matter volume in a bilateral parieto-occipital cluster and a right parieto-occipital cluster ( P s &lt; 0.001). Conversely, the fragile X group showed significantly smaller gray matter volume in the bilateral gyrus rectus ( P  &lt; 0.03). Associations between these regional brain volumes and key socio-emotional variables provide insight into gene–brain–behavior relationships underlying the fragile X syndrome phenotype in females. These findings represent the first characterization of a neuroanatomical phenotype in a large sample of girls with fragile X syndrome and expand our knowledge about potential neurodevelopmental mechanisms underlying cognitive–behavioral outcomes in this condition.

Neuroanatomical Profile of Young Females with Fragile X Syndrome: A Voxel-Based Morphometry Analysis