Longitudinal identification of clinically distinct neurophenotypes in young children with fragile X syndrome

Significance We present a research study that uses early structural brain growth as a metric for defining subgroups within individuals with fragile X syndrome (FXS). Topological data analysis, a type of multivariate pattern classification, identified two large subgroups based solely on the longitudinal structural brain images. Post hoc analysis indicated significant, unidirectional differences in cognition, adaptive functioning, and autism severity scores. Our results support the use of longitudinal topological data analysis (TDA) as a putative tool for differentiating individuals with FXS based on neuroanatomical data. This information may be used to predict outcomes and guide design of targeted therapies for individuals with FXS. Longitudinal TDA may be a useful analysis tool to explore variation in other neuropsychiatric disorders.