The Impact of Heritable Myopathies on Gastrointestinal Skeletal Muscle Function

Among other contributions to gastrointestinal (GI) function, skeletal muscles regulate transit at both ends of the GI tract by providing propulsive forces for ingested nutrients and controlling the excretion of waste products. At the oropharynx, skeletal muscles provide necessary forces for effective mastication and the transfer of food boluses from the mouth into the proximal esophagus, where skeletal muscle-mediated peristalsis initiates propulsion of food boluses towards the stomach, a function supplanted by the upper esophagus smooth muscle. Consequently, the most prominent manifestation of proximal GI tract skeletal muscle dysfunction is transfer and oropharyngeal dysphagia that may result in repeated episodes of life-threatening choking and pulmonary aspiration. At the anal canal, the external anal sphincter controls the release of gas, liquids, and solids. Skeletal muscles within the pelvic floor play a synergistic role in regulating defection. Hence, distal GI tract skeletal muscle dysfunction may result in the leakage of flatus and fecal matter, whereas, in contrast, pelvic floor dysfunction may contribute to constipation. The balance between such defects may severely impact nutritional status and quality of life. Herein, we provide a comprehensive review of the genetics, molecular biology, and mechanisms underlying heritable disorders of skeletal muscle and how these may impact GI tract function and overall well-being. For organizational purposes, we separate discussions of congenital, mitochondrial, and myofibrillar myopathies and muscular dystrophies. For the sake of completeness, we also briefly consider acquired myopathies that affect GI tract function. As treatment options are currently limited, disorders of skeletal muscle function provide exciting therapeutic opportunities, including innovative approaches to target specific gene modifications.