Immunohistochemical Characterization of Facioscapulohumeral Muscular Dystrophy Muscle Biopsies.
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.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS ; Department of Neurology, University of Rochester Medical Center, Rochester, NY.
Jeffrey M
JM
Statland
Department of Neurology, University of Rochester Medical Center, Rochester, NY.
Karen J
KJ
Odrzywolski
Department of Neurology, University of Rochester Medical Center, Rochester, NY.
Bharati
B
Shah
Department of Neurology, University of Rochester Medical Center, Rochester, NY.
Don
D
Henderson
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY.
Alex F
AF
Fricke
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
Silvère M
SM
van der Maarel
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.
Stephen J
SJ
Tapscott
Department of Neurology, University of Rochester Medical Center, Rochester, NY.
Rabi
R
Tawil
Facioscapulohumeral muscular dystrophy; apoptosis rates; capillary density; myonuclear density; satellite cell counts