- Clinical science
Muscular dystrophies are a group of progressive diseases that affect the musculoskeletal system. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive diseases, whereas limb-girdle muscular dystrophy (LGMD) may be either autosomal dominant or recessive, and facioscapulohumeral dystrophy (FSHD) is usually autosomal dominant. Muscular dystrophies are commonly due to mutations involving muscular genes (e.g., dystrophin-protein coding gene). Patients typically present with muscular complaints affecting specific muscle groups, particularly the pelvic girdle musculature. DMD is the most severe form of muscular dystrophy, with disease onset typically occurring at two to three years of age. BMD usually does not become evident before the age of 15. DMD progresses rapidly and typically leads to ambulatory inability by age 12. Diagnosis of DMD and BMD is established based on blood tests that show increased creatinine kinase, whereas diagnosis of LGMD and FSHD is mainly based on genetic analysis. Treatment of muscular dystrophies is usually supportive and includes physiotherapy, assistive devices (e.g., wheelchair), and psychological support. The life expectancy for patients with DMD is approx. 30 years, whereas patients with BMD and LGMD have a longer life expectancy.
- Inheritance pattern (DMD and BMD): X-linked recessive
- Chromosomal mutations affecting the dystrophin gene on the short arm of the X chromosome (Xp21)
- Dystrophin protein: anchors the cytoskeleton of skeletal and cardiac muscle cells to the extracellular matrix by connecting cytoskeletal actin filaments to membrane-bound α- and β-dystroglycan, which are connected to extracellular laminin
Dystrophin gene: largest known protein-coding gene in the human DNA
- Because of its size, the dystrophin gene is at increased risk for spontaneous mutations.
- Mutations affecting the dystrophin gene→ alterations of dystrophin protein structure → partial (BMD) or almost complete (DMD) impairment of protein function → disturbance of numerous cellular signaling pathways → necrosis of affected muscle cells → replacement with connective tissue and fatty tissue → affected muscles are weak even though they appear larger (“pseudohypertrophy”)
Duchenne is caused by Deleted Dystrophin.
- Progressive muscle paresis and atrophy
- Weak reflexes
- Waddling gait (i.e., ) with bilateral
- The individual arrives at a standing position by supporting themselves on their thighs and then using the hands to “walk up” the body until they are upright.
- Classic sign of DMD, but also occurs in inflammatory myopathies (e.g., dermatomyositis, polymyositis) and other muscular dystrophies (e.g., BMD)
- Calf pseudohypertrophy (see pathophysiology above)
- Inability to walk by approx. 12 years of age
- Cardiac and respiratory muscle involvement
- Cognitive impairment
- In late stages: nocturnal hypoventilation, dysphagia, vomit, diarrhea, and constipation; rarely intestinal pseudo-obstruction
- Symptoms similar to those of DMD, but less severe
- Slower progression (patients often remain ambulatory into adult life)
- Heart involvement is more common compared to DMD.
“Becker is Better.”
- Blood tests:
- Genetic analysis (confirmatory test): detect dystrophin gene mutation
- Muscle biopsy
- Definition: a complex genetic disorder characterized by progressive muscle weakness of the face, scapula, upper arm
- Epidemiology: the third most common type of muscular dystrophy
- Clinical features
- Diagnosis: genetic testing to detect the D4Z4 short repeat array
Limb-girdle muscular dystrophy (LGMD) 
- Definition: a genetic disorder characterized by progressive muscle weakness that primarily affects the pelvic and shoulder girdle
- Clinical features
- Elevated CK
- Muscle biopsy shows a decrease in protease calpain 3
- Genetic analysis to detect the underlying mutation
The differential diagnoses listed here are not exhaustive.
- Medical therapy
- Supportive therapy
- Life expectancy is approx. 30 years.
- Cardiac or respiratory failure is usually the cause of death.
- Life expectancy is 40–50 years.
- Cardiac failure is typically responsible for the reduced life expectancy.