The characteristic lesions in the congenital myopathies are revealed most clearly by the systematic application of histochemical stains to frozen sections of muscle biopsy tissue and by phase and electron microscopy. Some of the abnormalities are also disclosed by the conventional stains used in light microscopy, but as a group their identification has been the product of newer histologic techniques.
A word of caution is in order about the specificity of some of the morphologic changes and the classifications of the congenital myopathies based on these changes. It is inadvisable to assume that a change in a single organelle or a subtle change in the sarcoplasm of a muscle fiber can be relied on to characterize a pathologic process. Indeed, as more careful studies have been made of this class of disease, the specificity of some of the changes has come to be questioned. For example, central cores are sometimes found in the same muscle as nemaline bodies, and so on, and each of the denotative lesions has been reported in association with other systemic diseases and even as a result of certain medications. Nevertheless, the prominence of the morphologic change in any individual case, along with certain characteristic clinical features, permits an accurate diagnosis to be made.
In the original family described by Shy and Magee, 5 members (4 males) in 3 successive generations were affected, suggesting an autosomal dominant pattern of inheritance. The youngest was 2 years old; the oldest, 65 years. In each there was weakness and hypotonia soon after birth (again, “floppy infant”) and a general delay in motor development, particularly in walking, which was not achieved until the age of 4 to 5 years. These patients had difficulty in rising from a chair, climbing stairs, and running. The weakness was greater in proximal than in distal muscles, although the latter did not escape, and shoulder-girdle muscles were affected less than those of the pelvic girdle. Facial, bulbar, and ocular muscles were spared. The tendon reflexes were hypoactive and symmetrical. Muscle atrophy was not a prominent feature, although poor muscular development was present in 1 patient and has since been reported in others. There were no fasciculations, cramps, or myotonia, but cramps following exercise have been described in other families. The ECGs were normal.
Almost all cases studied in the modern era have been due to variants in the ryanodine receptor 1 (RYR1), which is also implicated in the causation of a small number of cases of malignant hyperthermia (see Chap. 41) and of the rare recessively inherited condition of minicore disease (multiple, or multi-minicore), a congenital myopathy that may include ophthalmoplegia. The disease therefore has remarkable attribute in that every patient is a potential candidate for the development of malignant hyperthermia and should wear a bracelet or be otherwise identified to indicate vulnerability to this anesthetic-induced complication.
The disease is rare, but as additional cases have been discovered, milder forms have come to be recognized, and in some of them the symptoms first appeared in adult life. Originally these patients were thought to have limb-girdle dystrophy because of the disproportionate involvement of proximal muscles. In other families, such as the one reported by Patterson and colleagues, the disease was first recognized in middle adult life with the rapid evolution of a proximal myopathy. Dislocation of the hips, pes cavus or pes planus, and kyphoscoliosis has been found in a few children, but arthrogryposis is rare. In the majority of cases, the progress of the disease is extremely slow, with slight worsening over many years. These represent the two extremes of the process.
The EMG reveals brief, small-amplitude motor unit potentials with a normal interference pattern. Serum concentration of CK is normal or only slightly elevated, as it is in all the congenital myopathies.