Muscular Dystrophies and Other Muscle Diseases¶
Chapter 460 | Part 13: Neurologic Disorders
KEY CLINICAL POINTS¶
- Muscular dystrophies are genetically heterogeneous, progressive disorders characterized by muscle weakness and atrophy.
- Key patterns of weakness include proximal (limb-girdle), distal, axial, and facial/neck involvement.
- Diagnostic evaluation involves clinical assessment, laboratory tests (CK, EMG), imaging (MRI), and genetic testing.
- Treatment is primarily supportive, with corticosteroids for Duchenne/Becker muscular dystrophy and gene therapy in experimental phases.
- Differential diagnosis includes myopathies, metabolic disorders, and neuromuscular junction diseases.
1. DEFINITION & OVERVIEW¶
Muscular dystrophies are a group of hereditary progressive disorders characterized by muscle weakness, atrophy, and structural muscle abnormalities. Other muscle diseases include inflammatory myopathies, metabolic myopathies, and neuromuscular junction disorders. The pattern of muscle involvement (proximal, distal, axial) is critical for differential diagnosis.
Table 460-1: Myopathies by Pattern of Weakness/Muscle Involvement¶
| Pattern of Weakness | Associated Conditions |
|---|---|
| Proximal (Limb-Girdle) | Duchenne/Becker muscular dystrophy, LGMD, myotonic dystrophy |
| Distal | Distal myopathies, OPMD, Miyoshi disease |
| Axial | Emery-Dreifuss dystrophy, inclusion body myositis |
| Facial/Neck | FSHD, oculopharyngeal dystrophy |
| Myotonia | Myotonic dystrophy, congenital myotonia |
1.1 Clinical Features¶
Proximal weakness (limb-girdle), facial/neck weakness, muscle stiffness, and fatigue are common. Myotonia, contractures, and pseudohypertrophy may occur. Cardiac and respiratory involvement is frequent in dystrophies.
1.2 Pathophysiology¶
Genetic mutations affect structural proteins (e.g., dystrophin, sarcoglycans) or metabolic pathways (e.g., glycolysis, lipid metabolism). Defects in sarcolemma integrity or mitochondrial function lead to muscle degeneration.
2. EPIDEMIOLOGY¶
Duchenne muscular dystrophy (DMD) affects ~1 in 3000 males. Becker muscular dystrophy (BMD) is less severe, with prevalence ~5 per 100,000. Limb-girdle muscular dystrophies (LGMD) have prevalence 1.63 per 100,000. Myotonic dystrophy (DM) is autosomal dominant with variable penetrance.
2.1 Risk Factors¶
Family history of muscular dystrophy, consanguinity, and certain ethnic backgrounds (e.g., French-Canadian, Ashkenazi Jews) increase risk for specific subtypes.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Genetic mutations in structural proteins (e.g., dystrophin, sarcoglycans) or metabolic enzymes (e.g., phosphofructokinase) cause muscle degeneration. Defects in sarcolemma integrity or mitochondrial function lead to energy failure and muscle necrosis.
Table 460-3: Autosomal Dominant Limb-Girdle Muscular Dystrophies¶
| Gene | Protein | Clinical Features |
|---|---|---|
| MYOT | Myotilin | Rippling muscle disease |
| LMNA | Lamin A/C | Emery-Dreifuss dystrophy |
| CAV3 | Caveolin-3 | LGMD1C |
| DES | Desmin | LGMD1E |
3.1 Genetic Causes¶
DMD/BMD: Dystrophin gene mutations. LGMD: Mutations in genes like CAPN3, DYSF, FKRP. Myotonic dystrophy: CTG trinucleotide repeats in DMPK gene.
4. CLINICAL FEATURES¶
Proximal muscle weakness, gait abnormalities (e.g., waddling gait), and fatigue are common. Myotonia, contractures, and pseudohypertrophy may occur. Cardiac and respiratory failure are leading causes of mortality in dystrophies.
4.1 Myotonia¶
Myotonia is prolonged muscle contraction followed by slow relaxation. It is prominent in DM1, congenital myotonia, and paramyotonia congenita.
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish from myopathies, metabolic disorders, and neuromuscular junction diseases. Key differentiators include pattern of weakness, family history, and response to specific therapies (e.g., corticosteroids for LGMD).
5.1 Patterns of Weakness¶
Proximal > distal (LGMD, DM), distal (OPMD, distal myopathies), axial (EDMD), and facial/neck (FSHD) are critical for diagnosis.
6. INVESTIGATIONS & DIAGNOSIS¶
Laboratory tests: Elevated CK, EMG (myopathic changes), muscle biopsy (rimmed vacuoles, ragged red fibers). Genetic testing for specific mutations. Imaging (MRI) for muscle involvement.
Table 460-2: Observations on Examination That Disclose Muscle Weakness¶
| Functional Impairment | Muscle Weakness |
|---|---|
| Inability to forcibly close eyes | Upper facial muscles |
| Inability to raise arms above head | Proximal arm muscles |
| Inability to walk without waddling gait | Hip muscles |
| Inability to get up from floor | Hip, thigh, and trunk muscles |
6.1 Diagnostic Algorithms¶
For intermittent weakness: Forearm exercise test, CK levels, EMG, and genetic testing. For persistent weakness: MRI, muscle biopsy, and genetic analysis.
7. MANAGEMENT & TREATMENT¶
Supportive care includes physical therapy, orthoses, and respiratory support. Corticosteroids for LGMD and DMD. Gene therapy (e.g., exon skipping for DMD). For periodic paralysis: potassium supplementation, acetazolamide, and dietary management.
7.1 Specific Therapies¶
Duchenne/Becker: Corticosteroids, cardiac pacing, and ERT. Myotonic dystrophy: Mexiletine. Periodic paralysis: Potassium correction and avoidance of triggers.
8. PROGNOSIS & COMPLICATIONS¶
DMD leads to progressive weakness, cardiac failure, and early mortality. BMD has a milder course. Complications include respiratory failure, contractures, and cardiac arrhythmias. Myotonic dystrophy has a variable prognosis with intellectual disability and cardiac involvement.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid corticosteroids in late gestation. Pediatrics: Early intervention for ambulation. Elderly: Monitor for falls and frailty. Genetic counseling for hereditary forms.
9.1 Endocrine Disorders¶
Hyperparathyroidism, hypothyroidism, and diabetes can mimic myopathies. Hypokalemia may precipitate periodic paralysis.
10. KEY POINTS & CLINICAL PEARLS¶
- Pattern of weakness is critical for diagnosis. 2. Genetic testing is essential for hereditary myopathies. 3. Corticosteroids improve prognosis in LGMD and DMD. 4. Myotonia and periodic paralysis require specific management. 5. Early intervention prevents complications in dystrophies.