Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers: case series.

BACKGROUND: While an association between full mutation CGG-repeat expansions of the Fragile X Mental Retardation 1 (FMR1) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55-200 repeats) of the FMR1 gene may be overlooked.
OBJECTIVE: To report five FMR1 fXPCs cases with the hypermobile Ehlers-Danlos syndrome (hEDS) phenotype.
METHODS: We collected medical histories and FMR1 molecular measures from five cases who presented with joint hypermobility and loose connective tissue and met inclusion criteria for hEDS.
RESULTS: Five cases were female and ranged between 16 and 49 years. The range of CGG-repeat allele sizes ranged from 66 to 150 repeats. All had symptoms of hEDS since early childhood. Commonalities in molecular pathogenesis and coexisting conditions between the fXPCs and hEDS are also presented. The premutation can lead to a reduction of fragile X mental retardation protein, which is crucial in maintaining functions of the extracellular matrix-related proteins, particularly matrix metallopeptidase 9 and elastin. Moreover, elevated FMR1 messenger RNA causes sequestration of proteins, which results in RNA toxicity.
CONCLUSION: Both hEDS phenotype and premutation involvement may co-occur because of related commonalities in pathogenesis. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.