Later, weakness and atrophy spread to the muscles of the legs and forearms. The muscles that are preferentially affected among these are the neck flexors, wrist extensors, brachioradialis, costal part of the pectoralis major, latissimus dorsi, biceps, triceps, and anterior tibial and peroneal muscles. The ocular, facial, bulbar, and hand muscles are usually spared, although weakness of the facial and sternocleidomastoid muscles and of the diaphragm occurs in the late stages of the disease. As the trunk muscles atrophy, the bones stand out like those of a skeleton. The space between the lower ribs and iliac crests diminishes with atrophy and weakness of the abdominal muscles.
The limbs are usually loose and slack, but as the disability progresses, fibrous contractures appear as a result of the limbs remaining in one position and the imbalance between agonists and antagonists. Early in the ambulatory phase of the disease, the feet assume an equinovarus position as a result of shortening of the posterior calf muscles, which act without the normal opposition of the pretibial and peroneal muscles. Later, the hamstring muscles become permanently shortened because of a lack of counteraction of the weaker quadriceps muscles. Similarly, contractures occur in the hip flexors because of the relatively greater weakness of hip extensors and abdominal muscles. This leads to a pelvic tilt and compensatory lordosis to maintain standing equilibrium. The consequences of these contractures account for the habitual posture of the patient with Duchenne dystrophy: lumbar lordosis, hip flexion and abduction, knee flexion, and plantar flexion. As they become severe, these contractures contribute importantly to the eventual loss of ambulation. Scoliosis, as a result of unequal weakening of the paravertebral muscles, and flexion contractures of the forearms appear, usually after walking is no longer possible.
The tendon reflexes are diminished and then lost as muscle fibers disappear, the ankle reflexes being the last to go. The bones are thin and demineralized, and the appearance of ossification centers is delayed. Smooth muscles are spared, but the heart is affected by various types of arrhythmias. The ECG shows prominent R waves in the right precordial leads and deep Q waves in the left precordial and limb leads, the result of cardiac fiber loss and replacement fibrosis of the basal part of the left ventricular wall (Perloff et al).
Death is usually the result of pulmonary infections and respiratory failure and sometimes, of cardiac decompensation. Patients with Duchenne dystrophy usually survive until late adolescence, but not more than 20 to 25 percent live beyond the twenty-fifth year. The last years of life are spent in a wheelchair; finally the patient becomes bedfast.
Mild degrees of developmental delay as mentioned, which is nonprogressive, are observed in many cases. The average IQ is 85 and approximately one-quarter have an IQ below 70, but the range has been 40 to 130.
As mentioned earlier, female carriers of the disease (i.e., the mothers of affected boys) and described slight weakness and enlargement of the calves as well as elevated CK values and abnormalities of the electromyelogram (EMG) and muscle biopsy, all slight in degree, in more than half; as mentioned, this is far higher than in our experience and that of our colleagues. A small number of female carriers manifest a moderate myopathy that may mimic limb-girdle dystrophy (see further on). The muscle fibers of such patients (referred to as manifesting or symptomatic carriers) show a mosaic immunostaining pattern mentioned earlier, some fibers containing dystrophin and others lacking it (Hoffman et al, 1988). This diagnostic information is particularly helpful in genetic counseling.