Myotonic syndromes

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

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