Flashcards in Disorders of Skeletal Muscle Deck (32):
Embryo review: What mesodermal structures give rise to skin, muscle, and bone? What are some signaling molecules that act on them to differentiate the cells?
Somites. Wnt, Shh, BMPs... all that.
What's delamination in the context of limb muscle development?
When undifferentiated cells of myotome leave and migrate into the growing limb. This uses genes. :P
What is the most mechanically stressed part of muscle?
The sarcolemma - specifically the interface between the muscle cell plasma membrane and the basement membrane.
What does a "floppy" baby actually mean? Is it more likely to be (non-dystrophy) myopathy or muscular dystrophy?
Floppy = hypotonic (muscles don't resist passive movement, may or may not be accompanied by loss of strength). More likely to be myopathy, as dystrophies have later onsets.
Name the 6 parts of the "neuraxis" to which you could localize a myopathy.
Brain (cortex and cerebellum), spinal cord, anterior horn cell, peripheral nerves, NMJ, muscle (and tendons/connective tissue)
What's the difference between a (congenital) myopathy and a dystrophy?
Distrophy is caused by aberrant breakdown and degeneration of muscle. Myopathy has no active breakdown, though the muscle is not fully functional.
Name the 4 "classical" congenital myopathies. Is each caused by a defect in one gene?
Central core disease
No, each one is genetically heterogeneous.
Name histologic features of nemaline myopathy
Red staining inclusions (in a modified Gomori Trichrome stain) in the muscle fibers.
What would you see in electron microscopy of nemaline myopathy?
Areas of big black threads between normal sarcomeres: "nemaline rods"
What does "nema-" mean? Relevance?
thread. Thread-like nemaline rods appear in EM of muscle biopsy of nemaline myopathy.
Nemaline myopathy is a disorder of what structures? What are some specific proteins involved (name 4-5ish).
Thin filaments. Nubulin, actin, tropomyosin 2 & 3, Troponin T, Cofilin-2
What is the mode of inheritance of nemaline myopathy?
Autosomal dominant or recessive: it depends on the gene responsible. Some, such as in actin, can be dominant-negative. Others are inherited recessively.
Why do myopathies and dystrophies often cause scoliosis?
Muscles on one side of back are weaker.
What are 3 thing's you'll see in muscular dystrophy histology?
Degeneration, regeneration (with hypertrophy) and infiltration with connective and fatty tissue.
Why are muscles bigger (pseudohypertrophy) in MD? (2 things)
Hypertrophy of intact muscle fibers.
Infiltration with fatty and connective tissue
What's a histologic feature of regenerating cells? Where does it come from?
Nucleus in center of muscle cell. These come from satellite cells.
What's the most common MD?
Duchenne MD. X-linked recessive.
What enzyme can you detect in the blood in Duchenne MD? Why is it there?
Creatine Kinase. Release when degenerating myocytes break open.
What are 3 major complications of Duchenne MD? Which one can we do least about?
Cardiomyopathy, respiratory insufficiency, scoliosis. Can support the latter two, but can't do much about the cardiomyopathy.
3 clinical features of Duchenne MD?
Progressive proximal weakness, pseudohypertrophy, elevated Creatine Kinase (CK)
What's the Gower's Maneuver?
From lying on back, child can't sit up and stand. Rather turns over, braces self with hands, and walks legs up to stand.
How might Duchenne MD be seen in gait?
Trendelberg sign: hip abductor weakness -> excessive hip swinging to compensate for drop (epecially when walking up stairs)
What's a more mild form of MD than Duchenne? Clinical signs? Major complication?
Becker MD. Weak muscles, calf pseuohypertrophy, high CK. Still can have cardiomyopathy.
Why might the dystrophin gene be so susceptible to mutation?
It's really big.
Is IQ affected by Duchenne MD? Practical implication?
Yes, the bell curve is shifted to the left. If you see mental retardation, you may want to consider Duchenne MD.
What does Dystrophin do?
Anchors a complex (dystrophin-associated proteins) that attaches myocyte plasma membrane to connective tissue.
What are revertant fibers in Duchenne MD? Why do they revert?
Fibers in MD patients that express dystrophin. Second mutation removes exon with frameshift - restoring functionality of protein.
What does staining for Dystrophin look like in a female carrier for Duchenne MD?
A small number of myocyte membranes will lack Dystrophin, due to lyonization. (can in rare cases cause significant myopathy)
What does dystrophin staining of myocytes look like in a patient with Becker MD?
present on all cells, but "irregular"
What's the difference in genetic cause between Becker and Duchenne MD? Significance?
Becker is an in-frame deletion, Duchenne's causes a frameshift. Becker MD is less severe because there is still protein present (it's just less functional / unstable).
What experimental Tx for Duchenne MD takes advantage of knowledge about revertant fibers?
Using an oligonucleotide to force exon-skipping, keeping the mRNA in-frame.