Chronic muscle weakness is a common complaint among patients seen in rheumatology and neuromuscular specialty clinics. This article focuses on adult-onset muscular dystrophies, select hereditary myopathies, and other neuromuscular conditions that must be distinguished from acquired causes of inflammatory muscle disease such as polymyositis. A few organizing principles help to focus the evaluation and narrow the differential diagnosis.

Because the onset of muscle weakness is typically quite insidious in genetically mediated conditions, the history provided by the patient may not at first fully reflect the degree and duration of muscle dysfunction. Individuals with long-standing and slowly progressive weakness are often able to make remarkable adaptations that permit them to function at home and in the workplace. These patients may not seek medical attention until some critical day-to-day function is finally severely impaired or lost. Because of this, it is important to question patients about physical performance and activity in relation to peers in childhood and adolescence, participation in organized sports or other physically demanding hobbies, and any physical accommodations that may have become necessary over time. These key areas of inquiry often establish a time course of disease that is much longer than initially reported. Family history may provide further diagnostic assistance; however, early parental death, variable penetrance of some diseases, recessive inheritance, de novo mutations, and other factors may obscure the genetic basis of a patient’s disorder. For this reason, even in the absence of family history, the possibility of a muscular dystrophy or other genetically mediated myopathy should be considered in any adult with chronic progressive muscle weakness.

The physical examination helps to eliminate other possible neurologic disorders. The appearance of the muscles and pattern of weakness is important. A proximal and symmetric distribution of weakness is most common. With a few notable exceptions discussed herein, marked asymmetry is uncommon in dystrophies and other hereditary myopathies, and should prompt consideration of central nervous system or peripheral nerve disorders. Other patterns, such as cranial or bulbar weakness and predominantly distal extremity weakness, can occasionally be observed. Prominent fasciculations or increased muscle tone are also unusual in hereditary muscle disease and suggest anterior horn cell or central nervous system disorders, respectively. Reflexes should be normal in myopathies or may be hypoactive if muscles are severely weak. Sensation should be normal, and the presence of objective sensory disturbances indicates that weakness is most likely related to peripheral nerve or central nervous system dysfunction.