Term
| Infantile Motor Neuron Disease is also called...? |
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Definition
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Term
Genetics of Spinal Muscular Atrophy
-mode of inheritance
-gene associated |
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Definition
-Autosomal recessive
-All forms of SMA are associated with mutations of SMN1, a gene required for motor neuron survival
-homozygous deletions of SMN1 cause SMA |
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Term
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Definition
Group of motor neuron diseases that are progressive neurologic illnesses that selectively destroys the anterior horn cells in the spinal cord and cranial nerve motor neurons
-begins in childhood or adolescence |
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Term
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Definition
SMA
Groups of round, atrophic fibers. The atrophy often involves an entire fascicle, a feature known as panfascicular atrophy.
There are also scattered large fibers that are two to four times normal size |
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Term
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Definition
SMA type 1
-onset at birth or within the first 4 mo.
-severe hypotonia, floppy
-death within first 3 years of life
SMA 2: onset 3-15 mo, death after 4 yrs
SMA 3: onset after 2yrs, survive into adulthood |
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Term
| Mode of Inheritance of Duchenne and Becker Muscular Dystrophy |
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Definition
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Term
| Progression and clinical presentation of Duchenne MD |
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Definition
Most common and most sever form of MD
-onset at 5 years
-wheelchair at 10-12 years
-relentless progression
-first sign is delayed walking, clumsiness, trouble keeping up with peers
-psuedohypertrophy due to enlarged muscles of the lower legs due to increased muscle fiber size, then increase in fat and connective tissue
-heart and cognitive impairments also seen
-death from respiratory insufficiency |
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Term
| Progression and clinical presentation of Becker MD |
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Definition
Onset in later childhood or adolescense, followed by slower and more variable rate of progression
-normal life span
-cardiac disease often seen |
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Term
| Gene and gene issues involved in Duchenne and Becker MD |
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Definition
DMD: gene located on Xp21, one of the largest human genes, 2.3 million bp
-encodes the protein dystrophin which is part of the sarcolemma-cytoskeltal protein complex
-without dystrophin, myocytes degenerate
-dystrophin is part of the interface btw intracellular contractile apparatus and the extracellular connective tissue matrix
-deletions, then frameshit and point mutations cause the problems
-2/3 of cases are familial, 1/3 are sporadic
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Term
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Definition
Duchenne Muscular Dystrophy
-variation in muscle fiber size
-regenerating fibers (blue hue)
-increased endomysial connective tissue
-increased numbers of internalized nuclei |
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Term
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Definition
Gene therapy not successful bc DMD gene is so huge
Successful in animals:
Stem cell injections directly into muscles
injection of viruses with genes that can makes small portions of the dystrophin protein |
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Term
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Definition
sustained involuntary contraction of a group of muscles
-the cardnial symptom of Myotonic Dystrophy
-"stiffness"
-difficulty releasing grip after a handshake, etc
-can be elicited by percussion of the thenar eminence |
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Term
| Genetic inheritance of Myotonic Dystrophy |
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Definition
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Term
| Molecular pathogenesis of Myotonic Dystrophy |
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Definition
-CTG trinucleotide repeat expansion which affects the mRNA for the protien kinase DMPK
-repeats accumulate with each generation (anticipation)
-the more repeats, the more severe the disease |
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Term
| Morphology of Myotonic Dystrophy |
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Definition
-Variation in SKM fiber size
-lots of internal nuclei
-ring fiber: subsarcolemmal bad of cytoplasm
-pathologic changes in the intrafusal fibers including fiber splitting, necrosis, regeneration |
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Term
| Clinical course of Myotonic Dystrophy |
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Definition
presents late childhood with gait abnormalities, weakness of foot dorsiflexors etc
-face muscle weakness and atrophy, ptosis
-cataracts |
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Term
| Ion Channel Myopothies and succinylcholine |
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Definition
| upon exposure to anesthetic mutations in the rynodine receptor cause the mutant receptor to allow uncontrolled eflux of calcium from the sarcoplam --> tetany, increased muscle metabolism, excessive heat production |
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