Skeletal muscle diseases

Muscular Dystrophies - Wasting Away Warriors

• Genetic disorders causing progressive muscle weakness and degeneration, primarily due to defects in muscle proteins.

• Duchenne Muscular Dystrophy (DMD)

  • X-linked recessive; frameshift deletion of dystrophin gene → absent dystrophin.
  • Onset < 5 years; Gowers sign, waddling gait.
  • Calf pseudohypertrophy (fibrofatty replacement).
  • ↑ CK; death from cardiomyopathy or respiratory failure.

• Becker Muscular Dystrophy (BMD)

  • X-linked recessive; non-frameshift mutation → partially functional dystrophin.
  • Milder, later onset than DMD.

• Myotonic Dystrophy Type 1

  • Autosomal Dominant; CTG repeat expansion in DMPK gene.
  • 📌 Mnemonic: My Tonia (can't release grip), My Toupee (balding), My Testes (atrophy), My Ticker (arrhythmia).

⭐ In Myotonic Dystrophy, the CTG repeat length correlates with disease severity and earlier onset in subsequent generations (anticipation).

Inflammatory Myopathies - Immune System Invasion

• Autoimmune muscle inflammation causing symmetric proximal weakness (except IBM). Labs: ↑ CK, ↑ aldolase, specific autoantibodies (e.g., anti-Jo-1, anti-Mi-2).

• Polymyositis (PM):

  • Endomysial inflammation via CD8+ T cells invading muscle fibers.

• Dermatomyositis (DM):

  • Perimysial inflammation (CD4+ T cells) causing perifascicular atrophy.
  • Skin signs: Heliotrope rash (eyelids), Gottron papules (knuckles).
  • 📌 DermatoMyositis = Disguised Malignancy.

• Inclusion Body Myositis (IBM):

  • Affects males > 50 years.
  • Asymmetric weakness, distal > proximal.
  • Histology: "Rimmed vacuoles."

⭐ Dermatomyositis in adults is a notorious paraneoplastic syndrome, often heralding an underlying malignancy (e.g., lung, ovarian, gastric).

NMJ Disorders - Synaptic Signal Failure

• Lambert-Eaton Myasthenic Syndrome (LEMS)

  • Pathophysiology: Autoantibodies target presynaptic voltage-gated Ca²⁺ channels → ↓ ACh release.
  • Association: High association with Small Cell Lung Cancer (SCLC).
  • Clinical: Proximal muscle weakness, depressed/absent reflexes, and autonomic dysfunction (dry mouth, impotence).
  • Key Sign: Strength and reflexes improve with repeated muscle stimulation (incremental response).

• Botulism

  • Pathophysiology: Clostridium botulinum toxin cleaves SNARE proteins, preventing presynaptic ACh vesicle release.
  • Source: Adults (improperly canned foods), infants (honey).
  • Clinical: Acute, symmetric, descending flaccid paralysis starting with cranial nerves.
  • 📌 Mnemonic (4 D's): Diplopia, Dysphagia, Dysphonia, Dysarthria.

⭐ Unlike Myasthenia Gravis, LEMS typically presents with proximal lower extremity weakness and shows an incremental response on repetitive nerve stimulation, reflecting increased ACh release with repeated firing.

Metabolic & Toxic Myopathies - Energy & Poison Problems

• Metabolic: Defective glucose/lipid energy use. Presents with exercise intolerance, painful cramps, myoglobinuria.
  • Glycogenoses (McArdle): ↓ myophosphorylase. Features "second wind" phenomenon during exercise.
  • Lipid Myopathies (CPT II def.): Weakness/myalgia triggered by fasting, fever, or prolonged exercise.
• Toxic: Direct myocyte injury from drugs/toxins.
  • Statins: Commonest cause. Myalgia, weakness, ↑CK.
  • Alcohol: Acute rhabdomyolysis or chronic proximal weakness.
  • Corticosteroids: Insidious onset of proximal weakness, Type II fiber atrophy.

⭐ Statin-induced immune-mediated necrotizing myopathy (IMNM) may persist after drug cessation; check for anti-HMG-CoA reductase antibodies.

• Duchenne muscular dystrophy is an X-linked recessive disorder from a dystrophin gene deletion, presenting with Gowers sign and calf pseudohypertrophy.
• Myotonic dystrophy, an autosomal dominant disease, is defined by CTG trinucleotide repeats, myotonia, and cataracts.
• Dermatomyositis presents with Gottron papules, a heliotrope rash, and proximal muscle weakness; associated with anti-Jo-1 antibodies.
• Myasthenia gravis features postsynaptic ACh receptor antibodies, causing muscle weakness that worsens with use.
• Lambert-Eaton syndrome has presynaptic Ca²⁺ channel antibodies, with weakness that improves with use, and is often a paraneoplastic syndrome of small cell lung cancer.