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
Expanded CUG repeats in mRNA → sequestration of MBNL1 (muscleblind-like protein) → abnormal alternative splicing of multiple genes including chloride channel (CLCN1) and insulin receptor → abnormal sarcolemmal ion channel function (chloride or sodium) → repetitive muscle fiber action potentials after voluntary contraction or percussion

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