Page 817 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Disorders of Skeletal Muscle 803

B1 B2

B3 B4

AB

CD

Figure 21–4 Patterns of skeletal muscle injury. A, Normal skeletal muscle has relatively uniform polygonal myofibers with peripherally placed nuclei
that are tightly packed together into fascicles separated by scant connective tissue. A perimysial interfascicular septum containing a blood vessel is
present (top center). B, Myopathic conditions often are associated with segmental necrosis and regeneration of individual myofibers. Necrotic cells
(B1-B3) are infiltrated by variable numbers of inflammatory cells. Regenerative myofibers (B4, arrow) are characterized by cytoplasmic basophilia and
enlarged nucleoli (not visible at this power). C and D, Clusters of both atrophic myofibers (C) (grouped atrophy) and fiber-type grouping (D), patchy
areas in which myofibers share the same fiber type, are features of neurogenic remodeling. The ATPase reaction shown in D is one method of distin-
guishing between fiber types, as type I fibers stain more lightly than type II fibers. Note loss of the “checkerboard” pattern (Fig 21–1, A).

The dystrophin gene spans roughly 2.4 megabases (about physical finding. The increased muscle bulk initially stems
1% of the X chromosome), making it one of the largest from myofiber hypertrophy, but as myofibers progres-
human genes. Its enormous size may explain in part its vulner- sively degenerate, an increasing part of the muscle is
ability to sporadic mutations that disrupt dystrophin produc- replaced by adipose tissue and endomysial fibrosis. Cardiac
tion. The most common mutations are deletions, followed muscle damage and fibrosis can lead to heart failure and
by frameshift and point mutations. Muscle biopsy specimens arrhythmias, which may prove fatal. Although no struc-
from patients with DMD show a complete absence of dys- tural abnormalities in the central nervous system have
trophin, whereas patients with BMD have mutations that been described, cognitive impairment is also sometimes
permit some dystrophin (albeit often a defective form) to be seen and may be severe enough to manifest as mental
made; thus, the severity of the disease correlates with retardation. Owing to ongoing muscle degeneration, high
the degree of the dystrophin deficiency. serum creatine kinase levels are present at birth and
persist through the first decade of life but fall as muscle
Clinical Features mass is lost during disease progression. Death results
Often the first symptoms of DMD are clumsiness and an from respiratory insufficiency, pneumonia, and cardiac
inability to keep up with peers due to muscle weakness. decompensation.
The weakness typically begins in the pelvic girdle and next
involves the shoulder girdle. Enlargement of the calf BMD becomes symptomatic later in childhood or ado-
muscles, termed pseudohypertrophy, is an important early lescence and progresses at a slower and more variable rate.
Many patients live well into adulthood and have a nearly
normal life span. Cardiac involvement can be the dominant