STEPTRACKERMUSCULOSKELETAL | PATHOLOGY + GENETICS + IMMUNOLOGY | HIGH-YIELD REVIEW

Muscle Disease

Inherited dystrophies, the inflammatory myopathies, and other causes of weakness with or without a raised CK.

FOCUS ON
Duchenne: X-linked frameshift deletion in dystrophin → boys < 5, Gowers sign, calf pseudohypertrophy, ↑↑ CK, dilated cardiomyopathy. Becker: in-frame, milder. Myotonic dystrophy: CTG repeat, can't release grip, cataracts, balding, conduction block. Dermatomyositis: heliotrope + Gottron + proximal weakness + cancer. Polymyositis: CD8, endomysial.
DISORDER
MECHANISM · GENETICS
FEATURES
CLUE
Duchenne muscular dystrophy
X-linked frameshift deletion in DMD (dystrophin, largest gene) → no dystrophin
Boys 2–5: proximal weakness, waddling gait, Gowers sign, calf pseudohypertrophy (fibrofatty); ↑↑ CK
Death from dilated cardiomyopathy/respiratory failure · steroids
Becker muscular dystrophy
In-frame deletion → partly functional dystrophin
Later onset (adolescence), milder, longer survival; cardiomyopathy
Western blot: reduced dystrophin
Myotonic dystrophy type 1
AD CTG repeat in DMPK (anticipation, maternal for congenital form)
Myotonia (can't release grip), distal and facial weakness, ptosis, frontal balding, cataracts, testicular atrophy, insulin resistance
Cardiac conduction defects → sudden death
Polymyositis
CD8 T cells invade endomysium → fiber necrosis
Symmetric proximal weakness over weeks–months; ↑ CK; no rash
Steroids · anti-Jo-1 antisynthetase syndrome
Dermatomyositis
Complement-mediated microangiopathy; CD4 T cells, B cells perimysial; perifascicular atrophy
Proximal weakness + heliotrope eyelid rash, Gottron papules, shawl sign, mechanic's hands; ↑ CK; anti-Mi-2
Screen for malignancy (ovary, lung, GI)
Antisynthetase syndrome
Anti-Jo-1 (histidyl-tRNA synthetase)
Myositis + interstitial lung disease + mechanic's hands + arthritis + Raynaud
Anti-MDA5 → rapid ILD
Inclusion body myositis
Degenerative + inflammatory; rimmed vacuoles
Men > 50: slow, asymmetric distal weakness (finger flexors) + quadriceps; falls
Steroid-resistant
Drug & endocrine myopathies
Toxic or metabolic injury
Statins (↑ CK, myalgia; worse with fibrates, CYP3A4 inhibitors); glucocorticoids (proximal weakness, normal CK); hypothyroidism (↑ CK)
Check TSH in myopathy
Polymyalgia rheumatica
Inflammatory synovitis/bursitis of girdles
Age > 50: shoulder and hip pain and stiffness, not weakness; ↑ ESR; normal CK
Giant cell arteritis association · low-dose prednisone
Mitochondrial myopathies
mtDNA mutations; maternal inheritance; heteroplasmy
Exercise intolerance, ophthalmoplegia; ragged red fibers; MELAS, MERRF
Lactic acidosis
McArdle disease
Myophosphorylase deficiency (glycogen storage V)
Exercise cramps, myoglobinuria, "second wind"; no lactate rise on ischemic exercise
Muscle glycogen can't be used

Mechanism — why dystrophin matters

Actin cytoskeleton
↔
Dystrophin
↔
Dystroglycan complex
↔
Laminin / ECM
No dystrophin
→
Membrane tears with contraction
→
Ca²⁺ influx, CK leak
→
Necrosis → fibrofatty replacementPseudohypertrophy

Frameshift (Duchenne) vs in-frame (Becker) explains the difference in severity, not the size of the deletion.

Inflammatory myopathies

FEATURE
POLYMYOSITIS
DERMATOMYOSITIS
INCLUSION BODY
Who
Adults
Adults, children
Men > 50
Pattern
Proximal, symmetric
Proximal + skin
Distal, asymmetric
Cells
CD8, endomysial
CD4/B cells, perimysial
CD8 + rimmed vacuoles
Clue
Anti-Jo-1
Heliotrope, Gottron, cancer
Finger flexors
Steroids
Respond
Respond
Don't respond

How it's tested

COMMON CONFUSIONPolymyalgia rheumatica causes pain and stiffness with normal strength and normal CK; polymyositis causes true weakness with high CK.
THE TRAPNew dermatomyositis in an adult warrants an age-appropriate cancer search — the rash can be the first sign of an ovarian or lung tumor.
YOUR APPROACHAge + inheritance → weakness pattern (proximal, distal, myotonia) → CK → skin, lung, heart clues → antibody or biopsy → drug or gene.

If you see… think…

4-year-old boy uses his hands to climb up his legs to stand → Gowers sign (Duchenne)
Big calves, ↑↑ CK, absent dystrophin → Duchenne muscular dystrophy
Teen with milder proximal weakness and reduced dystrophin → Becker
Can't let go after a handshake + cataracts + balding → myotonic dystrophy
Purple eyelids, knuckle papules, proximal weakness → dermatomyositis — screen for cancer
Myositis + ILD + cracked "mechanic's hands" → anti-Jo-1 antisynthetase syndrome
Older man with weak finger flexors, steroid-resistant → inclusion body myositis
Muscle pain and ↑ CK after adding gemfibrozil to a statin → statin myopathy
70-year-old with shoulder stiffness, ↑ ESR, normal CK → polymyalgia rheumatica
Ragged red fibers on Gomori trichrome → mitochondrial myopathy