Autonomic Function in Fragile X Syndrome: A Systematic Review

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Fragile X syndrome (FXS) is a primary genetic cause of intellectual disability and autism spectrum disorder.
• Individuals with FXS frequently exhibit anxiety and behavioral challenges, potentially linked to autonomic dysfunction.
• Autonomic nervous system function in FXS requires systematic investigation.

Purpose of the Study:

• To systematically review existing evidence on autonomic function in individuals with Fragile X syndrome.
• To consolidate findings on physiological measures of autonomic activity in FXS.
• To identify patterns and variations in autonomic function across the lifespan in FXS.

Main Methods:

• Conducted an electronic literature search across major databases (Medline, Embase, PsycINFO, Web of Knowledge).
• Included studies published before April 22, 2025, that physiologically measured autonomic function in FXS.
• Utilized a preregistered search strategy focusing on the autonomic nervous system in FXS.

Main Results:

• 28 studies met inclusion criteria, analyzing individuals aged <1 to 71 years.
• 75% of studies reported significant differences in autonomic function metrics between groups.
• Autonomic hyperarousal was observed in 86% of FXS participants, suggesting a consistent phenotype.

Conclusions:

• Autonomic hyperarousal is a prevalent clinical phenotype in Fragile X syndrome across all age groups.
• Further research should explore the link between sympathetic nervous system overactivation and clinical symptoms in FXS.
• Methodological variations and sample demographics currently limit direct comparison of study findings.