CASE 17: PROGRESSIVE PROXIMAL WEAKNESS, X-LINKED RECESSIVE
A 15-year-old boy, weak since early childhood, has been wheelchair-bound for 3 years. Apparently normal at birth, he did not walk until 17 months of age, and he never ran normally. By age 3, toe-walking and a waddling gait were evident, and he had difficulty climbing stairs and rising from a chair without using his arms. His stance was described as broad based, with a forward pelvic tilt and compensatory lumbar lordosis. By age 12, there was obvious scoliosis, which became progressively severe after he was confined to a wheelchair. He is an only child. His parents are neurologically asymptomatic, but a maternal uncle died in his mid-20s of a progressive neuromuscular disorder.
On examination, findings include scoliosis, scapular winging, and flexion contracture of the ankles, knees, hips, and elbows. Heel-cord shortening produces an equinovarus deformity of his feet. Limb and trunk muscles are severely wasted, particularly proximally; the calf muscles (gastrocnemii) have relatively preserved bulk. He is unable to rise from a chair, to stand unsupported, or to raise his arms against gravity; his neck flexors, pectoralis major, latissimus dorsi, biceps, triceps, wrist extensors, anterior tibialis, peronei, and gastrocnemii are prominently and bilaterally weak. Less weak are the muscles of his hands and feet. Facial muscles, speech, swallowing, and eye movements are normal. Tendon reflexes are absent except for a barely elicitable ankle jerk. Mentation is normal, as is sensation.
Serum creatine kinase level is 30 times normal. Nerve conduction velocities are normal. With intramuscular needle recording, the electromyogram (EMG) shows no fibrillations, fasciculations, or positive waves at rest; motor unit potentials during voluntary contraction of hand and foot muscles are polyphasic and of reduced amplitude and duration (Figure 12–1). Biopsy of the gastrocnemius reveals evidence of degeneration and regeneration, hyaline fibers, and replacement by fat and connective tissue with scattered muscle fibers of variable size, some abnormally small and some abnormally large. Immunocytochemical studies indicate that dystrophin is absent from muscle surface membranes. An electrocardiogram shows increased R-S amplitude in the right precordial leads and a deep Q wave in the left precordial leads. Southern blot analysis of the patient’s DNA reveals a deletion within the p21 region of the X chromosome. The mother’s serum creatine kinase level is mildly elevated, and she is hemizygous for the deletion.
Electrical recording from skeletal muscle reveals different profiles in neuropathies and primary muscle diseases. A. Typical activity in a normal muscle. The muscle fibers innervated by a single motor neuron are usually not adjacent to one another. When a motor unit potential is recorded by a needle electrode inserted into the muscle, the highly effective transmission at the neuromuscular junction ensures that each muscle fiber innervated by the same neuron will generate an action potential and contract in response to an action potential in the motor neuron. In the normal, resting muscle, there ...