Background: Posited pathological mechanisms in Facioscapulohumeral Muscular Dystrophy (FSHD) include activation in somatic tissue of normally silenced genes, increased susceptibility to oxidative stress, and induction of apoptosis. Objective: To determine the histopathological changes in FSHD muscle biopsies and compare to possible pathological mechanisms of disease.

Methods: We performed a cross-sectional study on quadriceps muscle biopsies from 32 genetically confirmed FSHD participants, compared to healthy volunteers and myotonic dystrophy type 1 as disease controls. Biopsies were divided into groups to evaluate apoptosis rates, capillary density, myonuclear and satellite cell counts. Results: Apoptosis rates were increased in FSHD (n= 10, 0.74%) compared to myotonic dystrophy type 1 (n= 10, 0.14%, P= 0.003) and healthy volunteers (n= 14, 0.13%, P= 0.002). Apoptosis was higher in FSHD patients with the smallest residual D4Z4 fragments. Capillary density was decreased in FSHD1 (n= 10, 316 capillaries/mm2) compared to healthy volunteers (n= 15, 448 capillaries/mm2, P= 0.001). No differences were seen in myonuclear or satellite cell counts. Conclusions: Preliminary evidence for increased apoptosis rates and reduced capillary density may reflect histopathological correlates of disease activity in FSHD. The molecular-pathological correlates to these changes warrants further investigation.