Key Clinical Updates in Myopathic Disorders
Casimersen is FDA-approved for treatment of Duchenne muscular dystrophy; it shows benefit in patients with a mutation amenable to exon 45 skipping.
ESSENTIALS OF DIAGNOSIS
Muscle weakness without sensory loss, often in a characteristic distribution.
Serum creatine kinase elevated in most cases.
Age at onset, time course, and inheritance pattern may suggest underlying disorder.
Myopathies can be inherited or acquired. Acquired myopathies often present acutely or subacutely while inherited myopathies are typically insidious in onset. Patients typically complain of weakness affecting proximal muscles, such as difficulty climbing stairs, arising from a chair, or reaching overhead, or of head drop. Sensory symptoms are absent. A detailed family history is required.
Examination shows weakness of proximal muscles. In some cases, there is a more specific pattern of weakness (eg, quadriceps and finger flexor weakness in inclusion body myositis). Extraocular muscle involvement is rarely seen, except in certain mitochondrial disorders, oculopharyngeal muscular dystrophy, and hyperthyroidism; when present, it should suggest the possibility of a neuromuscular junction disorder. Reflexes are normal or diminished in proportion to the degree of weakness. Sensation is normal.
Initial testing should include serum creatine kinase determination. Consider testing TSH, cortisol, vitamin D, and calcium. Antibodies specific to certain inflammatory myopathies and connective tissue disease can be checked when these conditions are suspected (see Chapter 20). Electromyography will reveal small motor units and early recruitment; it is helpful in confirming the localization of weakness to the muscle and suggesting a suitable site for biopsy, as does MRI. The electromyographic findings may be normal in corticosteroid and mitochondrial myopathies. Muscle biopsy establishes the diagnosis when inflammatory, mitochondrial, metabolic, or certain inherited myopathies are suspected. In cases where the family history or pattern of weakness suggests a specific genetic disorder, genetic testing can be pursued directly and biopsy may not be needed. Selected common and treatable myopathies are discussed below.
These inherited myopathic disorders are subdivided by mode of inheritance, age at onset, and clinical features, as shown in Table 24–10. In the Duchenne type, pseudohypertrophy of muscles frequently occurs at some stage; intellectual disability is common; and there may be skeletal deformities, muscle contractures, and cardiac involvement. A genetic defect on the short arm of the X chromosome has been identified in Duchenne dystrophy. The affected gene codes for the protein dystrophin, which is markedly reduced or absent from the muscle of patients with the disease. Dystrophin levels are generally normal in the Becker variety, but the protein is qualitatively altered. The diagnosis is usually made with genetic testing; muscle biopsy is needed occasionally. Duchenne muscular dystrophy can be recognized early in pregnancy in about 95% of women by genetic studies; in late pregnancy, DNA probes can be used on fetal tissue obtained for this purpose by amniocentesis. The ...