Muscular dystrophies

Muscular Dystrophies - An Overview

• Inherited genetic disorders causing progressive muscle weakness and degeneration, with muscle tissue replaced by fat and fibrous tissue.
• Classified based on mode of inheritance, age of onset, and distribution of weakness.
• Major types include:
  • Dystrophinopathies (Duchenne, Becker)
  • Myotonic Dystrophy
  • Limb-Girdle Muscular Dystrophies (LGMDs)
  • Facioscapulohumeral Dystrophy (FSHD)

⭐ Dystrophinopathies (DMD, BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene, primarily affecting males.

Duchenne MD - Gower's Power-Up Fail

• X-linked recessive disorder; mutation in the dystrophin gene (Xp21).
• Presents at 3-5 years with progressive proximal muscle weakness.
• Key Signs: Gower's sign, waddling gait, and calf pseudohypertrophy (fatty/fibrous infiltration).
• Investigations:
  • ↑↑ Serum Creatine Kinase (CK) > 10,000 U/L.
  • Muscle Biopsy: Absent dystrophin staining.
  • Genetic analysis is the gold standard.

⭐ Becker MD vs. Duchenne MD: Becker has a later onset and reduced dystrophin (not absent), leading to a milder phenotype. Cause of death in DMD is typically cardiorespiratory failure by age 20-30.

📌 Mnemonic: Duchenne = Deleted Dystrophin.

Becker MD - Duchenne's Kinder Cousin

• Genetics: X-linked recessive; in-frame dystrophin gene mutation. Produces a shorter but partially functional protein.
• Onset & Progression: Milder than DMD. Onset: 5-15 years. Slower progression; patients often ambulatory past 16 years, sometimes into their 30s.
• Clinical Features:
  • Progressive proximal muscle weakness (pelvic girdle).
  • Calf pseudohypertrophy.
  • Gower's sign is present.
• Complications: Cardiomyopathy is a significant cause of mortality.

⭐ Key Distinction: BMD results from an in-frame mutation (partially functional dystrophin), while DMD has a frameshift mutation (non-functional protein).

Myotonic Dystrophy - The Shake-It-Off Struggle

• Autosomal Dominant; CTG trinucleotide repeat expansion in DMPK gene.
• Myotonia: Delayed muscle relaxation (e.g., can't let go of handshake).
• Clinical Features: Progressive distal muscle weakness, "hatchet face" (temporal wasting, ptosis), dysphagia.
• Systemic Involvement:
  • Cataracts (iridescent "Christmas tree" type)
  • Frontal balding, testicular atrophy
  • Cardiac conduction defects (arrhythmias)

⭐ Anticipation: Disease severity increases & age of onset decreases in successive generations.

Other Types - The Supporting Cast

• Myotonic Dystrophy (DM1): Autosomal Dominant (CTG repeat). Myotonia (impaired muscle relaxation), distal weakness, “Christmas tree” cataracts, frontal balding, and cardiac conduction defects.

  ⭐ Genetic anticipation is characteristic: disease severity increases and age of onset decreases in successive generations.

• Facioscapulohumeral Dystrophy (FSHD): Presents with facial weakness (inability to smile/whistle), scapular winging, and upper arm weakness. Often asymmetric.
• Emery-Dreifuss (EDMD): 📌 Classic triad: early contractures (elbows, Achilles), slowly progressive weakness, and life-threatening cardiac conduction defects.

High-Yield Points - ⚡ Biggest Takeaways

• Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders affecting the dystrophin protein.
• Gower's sign (using hands to push off legs to stand) is a classic sign of DMD.
• BMD is a milder variant of DMD with a later onset and slower progression.
• Myotonic dystrophy, an autosomal dominant condition, is characterized by myotonia, cataracts, and cardiac issues.
• Limb-girdle muscular dystrophy presents with proximal muscle weakness in the shoulder and pelvic girdles.
• Serum Creatine Kinase (CK) is massively elevated in DMD/BMD.
• Glucocorticoids are the primary treatment to slow disease progression in DMD.