Learning Objective: By the end of this lesson, the learner will be able to differentiate Duchenne, Becker, and myotonic muscular dystrophies based on genetics, pathophysiology, clinical features, and age of onset, and recall key USMLE high-yield associations.
Duchenne Muscular Dystrophy (DMD)
- Inheritance: X-linked recessive
- Genetics: Frameshift or nonsense mutations in the dystrophin gene → truncated or absent dystrophin
- Largest protein-coding gene → high spontaneous mutation rate
- Pathophysiology: Dystrophin anchors muscle fibers to the ECM; absence → myonecrosis, progressive weakness
- Clinical Features:
- Onset <5 years; weakness starts in pelvic girdle → progresses superiorly
- Pseudohypertrophy of calves (fibrofatty replacement)
- Waddling gait, lordosis, Gowers sign (uses hands to stand)
- Dilated cardiomyopathy → common cause of death
- Diagnostics: ↑CK and aldolase; confirm with genetic testing
Mnemonic: “Duchenne = Deleted dystrophin”
Becker Muscular Dystrophy (BMD)
- Inheritance: X-linked recessive
- Genetics: Non-frameshift deletions → partially functional dystrophin
- Clinical Features:
- Onset in adolescence or early adulthood
- Milder than Duchenne; slower progression
- Overlap: Some deletions in the dystrophin gene can cause either Duchenne or Becker
Myotonic Dystrophy
- Inheritance: Autosomal dominant
- Genetics: CTG trinucleotide repeat in DMPK gene → abnormal myotonin protein kinase
- Clinical Features:
- Onset 20–30 years
- Myotonia: difficulty releasing grip (percussion myotonia)
- Muscle wasting, cataracts
- Testicular atrophy, frontal balding (CATG mnemonic: Cataracts, Toupee, Gonadal atrophy)
- Cardiac arrhythmias
- Muscle biopsy: Ring fibers, central nuclei
High-Yield USMLE Tips
- Duchenne vs Becker: Duchenne = earlier, severe, deleted dystrophin; Becker = milder, partially functional dystrophin
- Gowers sign = classic for Duchenne; also in other myopathies
- Myotonic dystrophy = AD, adult-onset, multi-system → cataracts, frontal balding, testicular atrophy
