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Inheritance pattern and molecular understanding are really HY for USMLE
- Both Duchenne and Becker are X-linked recessive.
- Caused by mutations in the dystrophin gene (DMD).
- Dystrophin is a large cytoskeletal protein inside skeletal muscle that stabilizes the cytoskeleton with the extracellular matrix.
- Dystrophin binds to a transmembrane protein called beta-dystroglycan.
- The dystroglycan-dystrophan complex is necessary for normal skeletal muscle cell integrity.
| USMLE wants you to know that Duchenne is usually caused by a frameshift mutation (i.e., 1 or 2 bp deleted or inserted).
In contrast, Becker is usually not caused by a frameshift (i.e., a missense mutation, or deletion/insertion in repeats of 3 bp, etc.). |
Age of onset and the Gower maneuver
- You need to know that Duchenne is worse than Becker.
- Questions on Duchenne will almost always mention a young boy, whereas for Becker they’ll almost always mention a teenager or adult.
- Boys who have Duchenne classically exhibit the Gower maneuver. This is described as walking backwards with the arms in order to stand up. You will not see the Gower maneuver being described in a patient with Becker; on the Step1, this is Duchenne only.
Psuedohypertrophy and affected muscles
- All hypertrophy that occurs is followed by pseudohypertrophy, which is fibroadipose deposition in the muscle.
- Despite the seemingly enlarged muscle size, patients progress to profound weakness.
- Asymmetrical weakening of paraspinal muscles leads to kyphoscoliosis.
- The USMLE-tested cause of death from both diseases is cardiomyopathy/heart failure.
| Pseudohypertrophy = fibroadipose replacement of the muscle.
Biopsy shows fibrous and fatty tissue; it also shows variation in fiber diameter and ↑ # of internalized nuclei + fiber regeneration / degeneration. |
- The muscular dystrophies tend to affect pelvic girdle muscles and calves first.
- If they ever ask you which location the weakness starts first, and calves and hips are both answers, hips are correct over calves.
- Most students get this wrong because these patients are classically photographed for having massively hypertrophied calves, but the calves are typically not the first place affected.
Miscellaneous
- One last point about the DMD gene is that it is the longest human gene. This means if they ever ask you which gene would be most likely to undergo a spontaneous mutation, the answer is DMD.
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