Genetic diseases of muscle
Section snippets
The muscular dystrophies
The muscular dystrophies are a group of inherited diseases of muscle which are quite heterogeneous in their severity and involvement of specific muscle groups but which share some common features (Table 1). Most are due to the absence or altered function of a structural component of the muscle fiber. The muscle undergoes dystrophic changes characterized by repetitive rounds of necrosis, degeneration and regeneration resulting in remodeling of the muscle tissue with fibrosis and fatty
The myotonic dystrophies
The myotonic dystrophies are progressive, heritable muscle disorders with several unique features to warrant distinction from the other muscular dystrophies (Table 2). Along with muscle weakness and wasting, patients have myotonia, a painless sustained muscle contraction, which can be elicited by forceful contraction or percussion of muscles. The disorders affect multiple organ systems in addition to muscle. Recent genetic discoveries suggest novel molecular explanations for the multisystem
The congenital muscular dystrophies and myopathies
Classification of congenital muscular dystrophies (CMD) and congenital myopathies (CM) has been a troublesome task for decades. As their names imply, the disorders share a common onset of muscular weakness at birth. The CMDs and CMs were originally distinguished from one another by the apparent progression of the dystrophies and static course of the myopathies. However, it is now clear that this distinction is not always accurate, particularly with lack of progression found in many CMD patients
The distal myopathies
In contrast to most myopathies and muscular dystrophies that have a pattern of weakness involving predominantly proximal muscles, the distal myopathies begin with weakness in the forearms, hands and lower legs (Table 4). For unknown reasons, histochemical analysis reveals a disproportionate share of autophagocytic vacuoles in the skeletal muscle of these patients. The diseases are sporadic and inherited. Original observations of affected families suggested the diseases were restricted to
Summary
In the last twenty years, the genetic basis for most of the inherited myopathies and muscular dystrophies has been unveiled. Diseases have been found to result from loss of function of structural components of the muscle basal lamina (eg, MCD1A), sarcolemma (eg, the sarcoglycanopathies), nucleus (eg, EDMD) and sarcomere (eg, the nemaline myopathies). A few have been associated with abnormalities in the genes for muscle enzymes (eg, calpain and fukutin). Alternate mechanisms of pathogenesis have
Acknowledgements
Thanks to Drs. Kenneth Fischbeck and Thomas Crawford for critical reading of the manuscript, to Jeff Ritzmann for digital artwork and to Tina Cuda for reference managing.
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Low muscle mass and strength in pediatrics patients: Why should we care?
2019, Clinical NutritionCitation Excerpt :Therefore, future studies using more accurate body composition techniques are required to elucidate the effect of fetal programming on muscle mass of the fetuses and newborns. Genetic diseases affect skeletal muscle development [40], with muscular dystrophy being the most commonly encountered group of myogenic disorders in pediatrics [41,42]. Muscular dystrophy is characterized by genetic defects of enzymes or proteins with structural, contractile or multifunctional properties, that leads to progressive and generalized muscle weakness, damage and wasting [41,42].
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2012, Anesthesia and Uncommon Diseases: Sixth EditionRestoration of γ-sarcoglycan localization and mechanical signal transduction are independent in murine skeletal muscle
2010, Journal of Biological ChemistryPhenotypic diversity arising from a single mutation
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2006, Neurology and Clinical Neuroscience: Text with CD-ROMMuscle diseases
2006, Anesthesia and Uncommon Diseases