Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence

Abstract

Introduction Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the FMR1 (fragile X messenger ribonucleoprotein 1) gene. The molecular understanding of the impact of the FMR1 gene mutation provides an opportunity to target treatment not only at symptoms but also on a molecular level.

Methods We conducted a systematic review to provide an up-to-date narrative summary of the current evidence for pharmacological treatment in FXS. The review was restricted to randomized, blinded, placebo-controlled trials.

Results The outcomes from these studies are discussed and the level of evidence assessed against validated criteria. The initial search identified 2377 articles, of which 16 were included in the final analysis.

Conclusion Based on this review to date there is limited data to support any specific pharmacological treatments, although the data for cannabinoids are encouraging in those with FXS and in future developments in gene therapy may provide the answer to the search for precision medicine. Treatment must be person-centered and consider the combination of medical, genetic, cognitive, and emotional challenges.