Latent Class Analysis Identifies Distinctive Behavioral Subtypes in Children with Fragile X Syndrome

Fragile X syndrome (FXS) is characterized by variable neurobehavioral abnormalities, which leads to difficulties in developing and evaluating treatments and in determining accurate prognosis. We employed a pediatric cross-sectional sample (1,072 males, 338 females) from FORWARD, a clinic-based natural history study, to identify behavioral subtypes by latent class analysis. Input included co-occurring behavioral conditions, sleep and sensory problems, autistic behavior scales (SCQ, SRS-2), and the Aberrant Behavior Checklist revised for FXS (ABC[subscript FX]). A 5-class solution yielded the most clinically meaningful, pharmacotherapy independent behavioral groups with distinctive SCQ, SRS-2, and ABC[subscript FX] profiles, and adequate non-overlap ([greater than or equal to] 71%): "Mild" (31%), "Moderate without Social Impairment" (32%), "Moderate with Social Impairment" (7%), "Moderate with Disruptive Behavior" (20%), and "Severe" (9%). Our findings support FXS subtyping, for improving clinical management and therapeutic development. [Written with the FORWARD Consortium.]