Conduct a review of qualitative literature in Fragile X Syndrome (FXS) in order to inform the development  of a conceptual model.

There is significant heterogeneity in the extent of behavioral and cognitive deficits across individuals with FXS, which poses significant challenges when developing a clinical outcome assessment strategy. A FXS conceptual model, which is a visual representation of key symptoms and associated impact concepts relevant to FXS, can be used for the development of a clinical outcome assessment strategy.

A strategic peer-reviewed literature search was conducted using the Medline®, Embase® and PsycINFO electronic databases to identify relevant symptom or impact concepts related to FXS. Additional source material included transcripts from previously conducted qualitative interviews with caregivers of individuals with FXS, online resources such as publicly available blogs and forums, supplementary searches conducted in Google Scholar, conference proceedings, and the reference lists of selected peer-reviewed articles.  

The symptom and impact concepts identified from the review were categorized into eight separate domains within the conceptual model: behavior, cognition, speech and communication, sensory perception, emotions, social, activities of daily living (ADL), and caregiver impacts.  Key symptom concepts included developmental delays in both learning and verbal communication, hyperactivity and impulsive behavior, and issues with short-term and working memory. The impact of symptoms associated with FXS included a lack of independence when completing ADLs, social behavior and communication issues, and emotional reactions such as anxiety and frustration.

Findings from the literature review, online materials and caregiver interviews were largely consistent and supported the development of the first known FXS conceptual model. The conceptual model provides a valuable resource to inform a clinical  outcome assessment strategy and identify key outcome measures for  potential use in FXS clinical trials.