Muscular Dystrophy: Overview of Types, Symptoms, and Management

A group of inherited, progressive neuromuscular disorders that are manifested in the death or degeneration of skeletal muscles. These disorders are caused by mutations in genes responsible for the production of proteins involved in muscle structure and function. The most common muscular dystrophy is Duchenne muscular dystrophy, which affects 1 in 5,000 men.

Classification of Muscular Dystrophy

Dystrophinopathies

• Duchenne Muscular Dystrophy (DMD):
  • Most common and severe form, primarily affecting boys.
  • Caused by mutations in the dystrophin gene.
  • Symptoms typically begin between ages 2 and 3, affecting the lower limbs first, followed by the heart and respiratory muscles.

• Becker Muscular Dystrophy (BMD):
  • A milder form of muscular dystrophy with symptoms appearing later, usually between ages 5 and 15.
  • Also caused by mutations in the dystrophin gene, it has a slower progression compared to DMD and primarily affects the hips and pelvic area.

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Clinical Signs in DMD and BMD

• Most commonly observed in boys; females are rarely affected unless there is unfavorable lyonization or a single X chromosome.
• Examination reveals:
  • Pseudohypertrophy of calf muscles (inverted bottle appearance).
  • Positive Valley sign: groove-like depression between pseudohypertrophied deltoid and infraspinatus muscles.
  • Positive Gower's sign: If a child with DMD and BMD (proximal muscle weakness) is asked to get up from a sitting position, he will first take help from his hands and put them on the ground, then take support from his legs and slowly take help from himself. The child will get up.
  • There can be exaggerated lumbar lordosis
  • These children can have varying degrees of intellectual disabilities
  • Cardio-respiratory compromise is usually the most common cause of mortality in these children

Non-Dystrophinopathies

• Limb-Girdle Muscular Dystrophy (LGMD): Is a number of inherited muscle diseases characterized by weakness and wasting of the muscles of the shoulders, pelvis, and hips. It is called the "limb girdle" because the muscles affected are located in the limb girdles, which are the bony structures that attach the arms and legs to the rest of the body.

• Characterized by weakness and wasting of shoulder and pelvic muscles.
• Rare disorder with a prevalence estimated between 1 in 14,500 and 1 in 123,000.

• Emery-Dreyfuss Muscular Dystrophy (EDMD): It is named after the two physicians who first described the condition, Alan Emery and Fritz Dreifuss. EDMD is a progressive disease that primarily affects males, although females can also be affected. Symptoms typically appear in childhood or adolescence.
  • A progressive disease affecting muscles and joints, primarily in males but also in females.
  • Symptoms include muscle weakness, contractures, joint stiffness, and cardiac issues.
• Facio-Scapulo-Humeral Muscular Dystrophy:
  •  Affects the face, shoulder blades, and upper arms, caused by mutations in the DUX4 gene.
• Myotonic Dystrophy:
  • Affects both genders, characterized by muscle weakness and difficulty relaxing muscles after contraction.

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Clinical Manifestations of Muscular Dystrophy

• Progressive muscle wasting
• Poor balance
• Spinal deformities (lumbar lordosis, kyphoscoliosis)
• Cardiomyopathy
• Progressive inability to walk
• Wobbly gait
• Deformed calves
• Limited range of activities
• Difficulty breathing
• Muscle cramps
•  Gover's sign: indicates weakness of the proximal muscles affecting the pelvic floor

Diagnosis & Investigations of Muscular Dystrophy

• Serum Creatine Kinase (CK): Normal value <160 IU/L; elevated in DMD and BMD.
• Genetic Evaluation:
  • Duchenne muscular dystrophy (DMD): Identifies deletions, duplications, or point mutations in the dystrophin gene.
  • Becker muscular dystrophy (BMD): Similar testing but with different mutation patterns.
  • limb-girdle muscular dystrophy (LGMD): Different genes are implicated, and panels of genes associated with different subtypes of LGMD may be analyzed.
  • Whole-exome/or whole-genome sequencing may also be used for more comprehensive testing or in cases where the specific subtype is unknown.
• Muscle Biopsy:
  • Indicated when clinical features suggest muscular dystrophy, but mutation analysis is negative.
  • Site: Vastus lateralis or gastrocnemius.
  • Histopathological examination shows early changes like myofiber necrosis and later stages with connective tissue proliferation.
  • On histopathology: Early changes are myofiber necrosis, scattered degenerating and regenerating mmyofibers, and mononuclear cells infiltrate. A few hypercontracted, dense fibers are also seen.
  • Later stages: Endomysial connective tissue proliferation and fibro-fatty deposits 
• Other Investigations:
  • Electromyography (EMG): EMG is a diagnostic test that measures the electrical activity of muscles. EMG can help to detect muscle damage and identify the pattern of muscle involvement in muscular dystrophies. EMG can also help to distinguish muscular dystrophy from other muscle disorders, such as myopathy.
  • Cardiac Assessment: ECG and echocardiography are essential for all DMD and BMD patients.

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Treatment of Muscular Dystrophy

• Supportive Care: Includes physiotherapy and management of cardiorespiratory issues.
• Pharmacological Management:
  • Newer drugs like Eteplirsen (exon skipping).
  • Corticosteroids (e.g., Prednisolone, Deflazacort) slow disease progression and improve muscle strength but have side effects.
  • Cardiovascular medications (ACE inhibitors/ARBs).
  • BiPAP and chest physiotherapy.
  • Nutritional support.
  • Use of nighttime ankle-foot orthoses (AFOs) and dynamic splints to prevent contractures.
  • Braces or surgical correction for scoliosis.

Newer Experimental Therapies

• Antisense Oligonucleotide (ASO) Therapy: Exon skipping therapy.
• Read-Through Therapy: Nonsense suppression.
• Gene Transfer Therapies: Using plasmids or adenoviruses (still experimental).
• Myostatin Inhibitors.
• PDE-5 Inhibitors.
• Idebenone.

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Complications

Key complications of muscular dystrophies include:

• Respiratory complications
• Cardiac complications
• Scoliosis
• Joint contractures
• Fractures
• Pressure sores
• Depression and anxiety

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