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There are a number of neuromuscular disease categories that cause hypotonia and weakness in infancy. Arranged in order of neuroanatomic localization, these include motor neuron diseases (eg, spinal muscular atrophy), neuropathies (eg, congenital hypomyelinating neuropathies), disorders of the neuromuscular junction (eg, congenital myasthenic syndrome), and muscle diseases. Major categories of muscle disease in infancy include congenital myopathies, congenital muscular dystrophies, congenital myotonic dystrophies, and glycogen storage diseases. Congenital myopathies and congenital muscular dystrophies are the subjects of this chapter.
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Muscular dystrophies share in common a set of histopathological findings consistent with muscle degeneration, including excessive fiber size variability, myofiber necrosis, myofiber regeneration and centralized nuclei, and infiltration of connective tissue and fat with rounded fibers. Congenital muscular dystrophies have traditionally been regarded as muscular dystrophies with congenital onset. Many of the protein products of genes implicated in congenital muscular dystrophy are involved directly or indirectly with the structures of the extracellular matrix.
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Congenital myopathies have traditionally been defined as a category of myopathies with onset at birth and histopathological findings of structural abnormalities in myofibers rather than the degenerative changes characteristic of congenital muscular dystrophies. The genetic etiologies of many, although not all, cases of congenital muscular dystrophies and congenital myopathies have been characterized. This genetic knowledge has revealed that later-onset variants exist for a number of subtypes. It is also becoming recognized that some muscle diseases of infancy share features of both congenital muscular dystrophy and congenital myopathy.
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Many, although not all, congenital muscular dystrophies are associated with structural brain malformations, central nervous system dysfunction, or eye abnormalities, distinguishing them from congenital myopathies, which are rarely associated with these complications. Patterns of weakness and contractures may also help assign subtype classifications in cases of congenital muscular dystrophy.
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The diagnostic evaluation of patients with suspected congenital muscular dystrophy or myopathy may be difficult as there is overlap between the phenotypes of the 2 categories of muscle disease, and other neuromuscular diseases (eg, spinal muscular atrophy) may be included in the differential diagnosis. All of these diseases may be associated with areflexia, hypotonia, and skeletal muscle weakness. Physical examination can help differentiate among these categories. For example, muscle weakness found in the face, extraocular muscles, or both may be suggestive of a congenital myopathy, whereas intact cranial nerves may be more consistent with spinal muscular atrophy. Eye abnormalities may suggest a congenital muscular dystrophy.
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Serum creatinine kinase (CPK, also known as CK) levels may be mildly elevated in congenital muscular dystrophy, congenital myopathy, and sometimes even spinal muscular atrophy, although more dramatic elevations are more suggestive of congenital muscular dystrophy. Aldolase is another muscle enzyme that can be measured in serum. The enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) are often measured in serum and are commonly referred to as “liver function tests,” but they are also ...