gms | German Medical Science

Objectives: Radial dysplasia (RD) affects approximately 1:8,000 live births. Recurrent 'wrist' deviation during growth affects all current treatment approaches; the underlying cause of this recurrence is unknown.

Previous animal work suggests connective tissue fibroblasts shape the developing limb musculature, and mutations restricted to these fibroblasts cause abnormal extracellular matrix production and reproduce the wider soft tissue anomalies seen in RD.

This study investigated intrinsic changes to limb connective tissue in RD patients, as a potential cause of the disease phenotype and recurrence.

Methods: Ethical approval and informed parental consent were obtained. Limb fascial biopsies from RD patients and age-matched normal controls (hand trauma patients) were dissociated and cultured in vitro. Extracellular matrix (ECM) proteins were fluorescently stained and both the ECM proteins expressed and their organisation were quantified. The ability of RD and control patient fibroblasts to shape muscle development was assessed by culture with a normal human muscle cell line.

Results: RD patient fibroblasts produced significantly less organised ECM than control fibroblasts (p<0.001). RD ECM differed in composition from control ECM, and was significantly less able to support organised muscle growth in culture.

Conclusions: These results support the hypothesis that there are intrinsic soft tissue changes in RD, which are developmentally distinct from the skeletal defects. These soft tissue changes plausibly contribute to recurrent 'wrist' deviation during growth, and present a target for both surgical and genetic treatment.