Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly-inherited myopathy, with estimated prevalence rates ranging from 1:8,000-20,000. As with other autosomal dominant diseases, alterations in gene expression are theorized to be responsible for the pathologic changes associated with FSHD. In fact, the overexpression of the double homeobox chromosome 4 gene (DUX4) is believed to lead to characteristic scapular winging and progressive muscular atrophy in the face, shoulder girdle, and truncal regions in the FSHD population. Despite continued research on the genetic etiology of FSHD in recent years, much remains to be learned regarding the functional implications and translational implications of the overexpression of the DUX4 gene. It has been shown that individuals with FSHD frequently exhibit pathophysiologic alterations in body composition, including high rates of skeletal muscle atrophy and fatty tissue infiltration. These factors are believed to contribute to the development of sarcopenic obesity, a condition which has been associated with an increased risk of disability and impairments in functional capacity. Further, in some clinical populations, sarcopenic obesity is believed to contribute to exercise intolerance. Exercise intolerance is reflected by a low peak oxygen consumption (VO2peak), an important indicator of health, and accompanied by dyspnea (labored breathing) and/or fatigue. Whether exercise intolerance is present among adults with FSHD is unknown, but is of high importance as exercise intolerance is strongly associated with morbidity and mortality in other clinical populations. Additionally, as muscle mass is a strong driver of metabolic rate, a low volume of lean tissue may also lead to pathologic alterations in metabolic function.
As such, this thesis had three aims, 1) to identify differences in the presence of sarcopenic obesity between people with FSHD and controls; 2) to explore variations in the severity of and mechanistic contributions to exercise tolerance, between adults with FSHD, and control groups; and 3) to identify differences in RMR between individuals with FSHD and controls. The results of this research showed that males with FSHD were more likely to meet diagnostic criteria for sarcopenic obesity than age- and sex-matched controls. Additionally, exercise intolerance was more likely to be present in people with FSHD, primarily due to differences in the volume of lean tissue between groups. Finally, based on this research, it appears that people wit FSHD have a resting metabolic rate that is lower than in controls, due to a low volume of lean mass. These observations stress the importance of lean tissue preservation amount people with FSHD, and lay the foundation for the development of exercise and nutrition-based therapeutic intervations within this clinical group.
University of Minnesota Ph.D. dissertation. July 2021. Major: Rehabilitation Science. Advisor: Manda Keller-Ross. 1 computer file (PDF); viii, 137 pages.
Anatomic, functional, and physiologic implications of altered body composition among people with Facioscapulohumeral muscular dystrophy.
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