| Feature | Progressive Muscular Dystrophies (PMD) | Myotonic Syndromes (MyD) | Mitochondrial Myopathies (Mito) |
|---|
| Primary Defect | Muscle protein gene defect (e.g., Dystrophin) | Trinucleotide repeat expansion | Mitochondrial DNA/nDNA gene defect |
| Inheritance | X-linked (DMD/BMD), Autosomal | Autosomal Dominant | Maternal (mtDNA), Autosomal (nDNA) |
| Weakness Pattern | Proximal > Distal | Distal > Proximal (DM1); Proximal (DM2) | Proximal, exercise intolerance |
| Myotonia | Absent | Present (grip, percussion) | Absent |
| Key Biopsy | Necrosis, fat/fibrous infiltration | Central nuclei, Type 1 atrophy (DM1) | Ragged Red Fibers |
| Systemic (Key) | Cardiomyopathy, respiratory failure | Multisystem (cataracts, cardiac, endocrine) | Multisystem (CNS, eye, ear, lactic acidosis) |
| CK | Markedly High | Mild-Mod High | Normal or Mild High |
| Buzzwords | Gower sign, calf pseudohypertrophy | ”Can’t let go,” hatchet face, anticipation | Ragged red fibers, maternal inheritance |
Etiology
- Autosomal dominant inheritence
- Type 1: CTG trinucleotide repeat expansion in the DMPK gene → changes in myotonin protein kinase expression
Clinical features
- Myotonia: delayed muscle relaxation following normal muscle contraction
- Classically manifests as difficulty releasing a handshake
- Skeletal muscle weakness (due to muscle atrophy)
- Myalgia
- Arrhythmia
- Cataracts
- Testicular atrophy or features of ovarian insufficiency (i.e., infertility)
- Frontal balding
- Cognitive and behavioral impairment