What are the different types of myopathy?

Types of Myopathy

Myopathies can be broadly classified into three major histopathological categories: myopathies, neuropathies, and mesenchymopathies, depending on whether they primarily affect smooth muscle cells, enteric neurons, or interstitial cells of Cajal, respectively. 1

Primary Myopathies

Congenital Myopathies

• Core Myopathies

  • Central core disease (CCD)
  • Multi-minicore disease (MmD)
  • Most commonly caused by mutations in RYR1 (ryanodine receptor 1) gene 1, 2
  • Characterized by cores (areas lacking oxidative enzyme activity) in muscle fibers

• Centronuclear Myopathies (CNM)

  • Characterized by abnormally located nuclei in the center of muscle fibers
  • Associated with mutations in DNM2 (dynamin 2), BIN1 (amphiphysin 2), and other genes 2, 3
  • Includes X-linked myotubular myopathy (MTM1 gene)

• Nemaline Myopathies

  • Characterized by rod-like structures (nemaline bodies) in muscle fibers
  • Multiple genetic causes including ACTA1, NEB, and KBTBD13 mutations 2, 4
  • Severity ranges from neonatal lethal to adult-onset forms

• Congenital Fiber Type Disproportion

  • Characterized by smaller type 1 muscle fibers compared to type 2 fibers
  • Various genetic causes including RYR1, TPM3, and SEPN1 mutations 5, 4

• Myosin Storage Myopathy

  • Characterized by hyaline bodies (myosin accumulation) in muscle fibers 1

Inflammatory Myopathies

• Polymyositis (PM)

  • Characterized by T-cell mediated muscle fiber invasion 1
  • Presents with proximal muscle weakness
  • No skin manifestations

• Dermatomyositis (DM)

  • Characterized by perifascicular atrophy and skin manifestations
  • Typical skin findings include Gottron's papules, heliotrope rash 1
  • Higher association with malignancy in adults

• Inclusion Body Myositis

  • Characterized by rimmed vacuoles and protein inclusions
  • Often affects distal muscles (especially finger flexors) and quadriceps
  • Generally resistant to immunosuppressive therapy

• Immune-Mediated Necrotizing Myopathy

  • Associated with anti-SRP or anti-HMGCR antibodies
  • Often triggered by statin use
  • Characterized by necrosis without significant inflammation

Secondary Myopathies

Systemic Disease-Associated Myopathies

• Connective Tissue Disorders

  • Systemic sclerosis (scleroderma): causes smooth muscle atrophy and gut wall fibrosis 1
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Still's disease

• Amyloidosis

  • Often associated with myeloma (lambda chains)
  • Can cause both myopathy and neuropathy 1
  • Hereditary forms present with peripheral neuropathy and cardiac involvement

• Endocrine Myopathies

  • Thyroid disorders (hypo/hyperthyroidism)
  • Hyperparathyroidism
  • Cushing syndrome 1

Toxic and Drug-Induced Myopathies

• Medication-Related

  • Statins
  • Steroids
  • Hydroxychloroquine 6
  • Colchicine

• Radiation-Induced Myopathy

  • Usually occurs after pelvic irradiation
  • Affects sigmoid and terminal ileal areas 1

Metabolic Myopathies

• Glycogen Storage Diseases

  • McArdle disease (type V)
  • Pompe disease (type II)
  • Characterized by exercise intolerance, cramps, and myoglobinuria 6

• Lipid Storage Myopathies

  • Carnitine deficiency
  • Carnitine palmitoyltransferase deficiency
  • Often present with exercise intolerance and rhabdomyolysis

Muscular Dystrophies

Dystrophinopathies

• Duchenne Muscular Dystrophy

  • X-linked recessive disorder (dystrophin gene)
  • Progressive proximal weakness starting in early childhood
  • Cardiac involvement common

• Becker Muscular Dystrophy

  • Milder variant of dystrophinopathy
  • Later onset and slower progression

Myotonic Dystrophies

• Myotonic Dystrophy Type 1 (DM1)

  • Caused by CTG repeat expansion in DMPK gene
  • Multisystem disorder with myotonia, muscle wasting, cataracts, cardiac conduction defects 1
  • Shows genetic anticipation (worsening in successive generations)

• Myotonic Dystrophy Type 2 (DM2)

  • Caused by CCTG repeat expansion in CNBP gene
  • Generally milder than DM1 with later onset (20-70 years) 1
  • Less severe cardiac involvement

Limb-Girdle Muscular Dystrophies

• Multiple genetic subtypes (LGMD1A-H, LGMD2A-Z)
• Primarily affects shoulder and pelvic girdle muscles
• Variable age of onset and progression

Cardiomyopathies

• Dilated Cardiomyopathy (DCM)

  • Characterized by dilated ventricle and global systolic dysfunction 6
  • Can be genetic, inflammatory, toxic, or idiopathic

• Hypertrophic Cardiomyopathy (HCM)

  • Characterized by massive ventricular hypertrophy without obvious cause 6
  • Most commonly caused by mutations in MYBPC3 and MYH7 genes

• Restrictive Cardiomyopathy (RCM)

  • Characterized by rigid ventricular walls with preserved systolic function
  • Impaired ventricular filling and diastolic dysfunction

• Arrhythmogenic Cardiomyopathy (ACM)

  • Primarily affects the right ventricle
  • Characterized by fibrofatty replacement of myocardium
  • Associated with desmosomal protein mutations 6

• Left Ventricular Non-Compaction Cardiomyopathy (LVNC)

  • Characterized by prominent trabeculations and deep recesses in the left ventricle 6

Diagnostic Approach

Diagnosis of myopathies typically involves:

1. Clinical evaluation and family history
2. Laboratory tests (CK, aldolase, inflammatory markers)
3. Electromyography (EMG) to confirm myopathic process 1
4. Muscle biopsy - gold standard for inflammatory myopathies 1
5. Genetic testing for hereditary myopathies
6. Imaging (MRI) to assess muscle involvement pattern
7. Cardiac evaluation when appropriate

Management Considerations

Currently, treatment for most myopathies is supportive, focusing on:

1. Multidisciplinary care with neuromuscular specialists 4
2. Respiratory support for those with respiratory muscle involvement
3. Cardiac monitoring for myopathies with cardiac involvement
4. Physical therapy to maintain function and prevent contractures
5. Immunosuppressive therapy for inflammatory myopathies
6. Genetic counseling for hereditary forms
7. Novel gene therapies are in development for specific genetic myopathies 7