Women who carry the FMR1 premutation are known to be at risk for several fragile X-associated conditions, but connective tissue problems have received relatively little attention. In this pilot study, we found that women with the premutation were much more likely than expected to show features resembling hypermobile Ehlers-Danlos syndrome, including joint hypermobility, chronic pain, and related connective tissue symptoms. Those with this connective tissue phenotype also reported more immune-related symptoms and showed physiological differences consistent with altered autonomic function. Although our study was small and larger studies are needed, these findings suggest that connective tissue manifestations may represent an underrecognized aspect of the fragile X premutation and deserve greater clinical and research attention. (https://jmg.bmj.com/content/early/2026/08/06/jmg-2025-111346)