Pseudohypertrophy in Duchenne Muscular Dystrophy
Pseudohypertrophy in DMD is the apparent enlargement of muscles—most characteristically the calves—caused by replacement of degenerating muscle tissue with fat and connective tissue rather than true muscle hypertrophy, creating a deceptively muscular appearance despite progressive weakness. 1
Pathophysiological Mechanism
The underlying process involves the dystrophin protein mutation leading to alternating areas of myocyte hypertrophy, atrophy, necrosis, and ultimately fibrosis with replacement of functional cardiomyocytes and skeletal muscle by connective tissue and fat. 1 This histological pattern creates the paradoxical clinical finding where muscles appear enlarged but are actually weaker and functionally impaired.
Clinical Distribution and Diagnostic Significance
Most Common Sites
- Calf muscles (gastrocnemius): Present in 94% of DMD patients, making it the most frequent and characteristic finding 2
- Infraspinatus muscle: Occurs in 88% of cases and is the second most common site of pseudohypertrophy 2
- Other affected areas: Deltoids, quadriceps, and tongue may also demonstrate pseudohypertrophy 1
Critical Diagnostic Value
Infraspinatus hypertrophy serves as an important alternative diagnostic sign when calf hypertrophy is absent or unremarkable, as documented in 5 DMD patients who lacked obvious calf enlargement but demonstrated infraspinatus pseudohypertrophy. 2 This finding should be actively sought during physical examination, particularly when DMD is suspected but classic calf hypertrophy is not evident.
Clinical Examination Technique
Examine muscles under mild contraction to detect subclinical pseudohypertrophy that may not be apparent at rest. 2 This technique increases diagnostic sensitivity and helps identify early or subtle cases of muscle involvement.
Associated Physical Findings
Pseudohypertrophy typically occurs alongside characteristic wasting patterns, particularly:
- Consistent wasting of muscles forming the anterior and posterior axillary folds 2
- Progressive proximal-to-distal muscle weakness 1
- Gowers' sign (difficulty rising from floor) 1
- Waddling gait 1
Differential Diagnosis Considerations
Pseudohypertrophy with calf involvement and scapular winging patterns can also occur in limb-girdle muscular dystrophy type 2 (LGMD2), particularly the sarcoglycan-deficient subtypes (LGMD2C, 2D, 2E, 2F). 1 However, LGMD2 typically has later onset (2-15 years) and more variable progression compared to DMD's earlier presentation around 3-5 years of age. 1, 3
Diagnostic Confirmation
When pseudohypertrophy is identified on examination:
- Immediately check serum creatine kinase levels, which are markedly elevated in DMD (often 10-100 times normal) 1
- Proceed with dystrophin deletion/duplication genetic testing 1
- Consider muscle biopsy if genetic testing is inconclusive, looking for absent dystrophin protein on immunocytochemistry and immunoblotting 1
Clinical Pitfall to Avoid
Do not mistake pseudohypertrophy for athletic muscle development or assume preserved strength based on muscle bulk. The enlarged appearance is misleading—these muscles are functionally weak and progressively degenerating. 1, 2 This misinterpretation can delay diagnosis and appropriate intervention, including timely initiation of glucocorticoid therapy which is the only medication proven to slow muscle strength decline and prolong ambulation. 1