56. www.freelivedoctor.com Limb Girdle Muscular Dystrophies Inheritance Locus Gene Clinicopathologic Features 1A Autosomal-dominant 5q31 Myotilin Onset in adult life with slow progression of limb weakness, but sparing of facial muscles; dysarthric speech 1B Autosomal-dominant 1q21 Lamin A/C Onset before the age of 20 years in lower limbs, progression during many years with cardiac involvement 1C Autosomal-dominant 3p25 Caveolin-3 (M-caveolin) Onset before the age of 20, clinically similar to type 1B 1D Autosomal-dominant 7p Unknown Limb girdle muscle weakness, adult onset 2A Autosomal-recessive 15q15.1-21.1 Calpain 3 Onset in late childhood to middle age; slow progression during 20–30 years 2B Autosomal-recessive 2p13.3-q13.1 Dysferlin Mild clinical course with onset in early adulthood 2C Autosomal-recessive 13q12 γ-Sarcoglycan Severe weakness during childhood, rapid progression; dystrophic myopathy on muscle biopsy 2D Autosomal-recessive 17q21 α-Sarcoglycan (adhalin) Severe weakness during childhood, rapid progression; dystrophic myopathy on muscle biopsy 2E Autosomal-recessive 4q12 β-Sarcoglycan Onset in early childhood, with Duchenne-like clinical course 2F Autosomal-recessive 5q33 δ-Sarcoglycan Early onset and severe myopathy; dystrophic myopathy on muscle biopsy 2G Autosomal-recessive 17q11-q12 Telethonin Distal weakness with limb-girdle weakness in late childhood to adulthood; rimmed vacuoles in muscle cells 2H Autosomal-recessive 9q31-q34.1 Tripartite motif-containing protein 32 (TRIM32) Limb-girdle and facial weakness with onset in childhood, mild, slowly progressive course
Smaller neurovascular triad, or “bundle”. How many axons are in this small nerve? Perhaps 5-8?
The more longitudinally a nerve happens to be sectioned, the more “wavy” it appears.
Electron microscope section, peripheral nerve. How many axons are myelinated? Perhaps about 7?
Please differentiate between microtubules (small circles) and neurofilaments (dots). Find the schwann cell nucleus, find an UNmyelinated axon, find a mitochondrion.
Note that the myelin “layering” has to start (INNER mesaxon) and end (OUTER mesaxon) somewhere!
It looks like one micrometer (micron) would span about 60 layers of myelin? True or false?
Slam dunk classical appearance of skeletal muscle. Why is skeletal muscle or voluntary striated muscle a better name for this than just striated muscle?
Is the peripheral nature of skeletal muscle nuclei more apparent from cross or longitudinal sections? Ans: Cross Why? Ans: Simple geometry! Are striations better seen on cross or longitudinal sections? Ans: Longitudinal Why? Ans: Simple geometry again!
EM, skeletal muscle, the sarcomere, like America, extends from “Z” to shining “Z”! Find glycogen. Find Mitochondria.
Find the sarcoplasmic reticulum, which is the endoplasmic reticulum of skeletal muscle. Find MYOSIN filaments, find ACTIN.
These are NONSPECIFIC reactions of nerve and skeletal muscle to injury
Extremely important concepts of nerve demyelinization, axonal damage, and regeneration
Muscle fiber necrosis
Muscle fiber vacuolization
Muscle fiber hypertrophy/atrophy. Certain fiber hypertrophy to make up for the loss of atrophic fibers
Why is auto-amputation common in severe leprosy? Ans: Nerve destructioon
CMT is a very HETEROGENEOUS group of hereditary diseases involved with defective myelination, e.g., CMT1, CMT2, CMT3, CMT4, X-linked CMT
Peroneal muscle involvement and HIGH arching is common in CMT.
BOTH demyelination AND a direct TOXIC effect to peripheral nerves are seen in diabetes, which is the MOST COMMON cause of neuropathy
Morton’s Neuromas most commonly occur in the 3 rd common digital branch of the MEDIAL plantar nerve, i.e., 3 rd and 4 th toe at the distal metatarsal level.
Schwannoma
Hypertrophy/Atrophy scenario
What is myotonia?
Dystrophin, an intracellular protein, forms an interface between the cytoskeletal proteins and a group of transmembrane proteins
Note again the atrophy/hypertrophy scenario
Half of dermatomyositis patients also have cancer, many are young adults and therefore there is a juvenile variant. Note the eyelid appearance and eyelid edema.
No skin changes, only in adults, no big association with cancer, and the inflammation is ENDOMYSEAL rather than PERIVASCULAR.
Very obscure disease, but said to be the most common acquired myopathy in people over the age of 50. Quads and wrist flexors, asymmetrically, is the rule.
Exceedingly RARE tumors, you may see, possibly ONE rhabdomyosarcoma in your life, perhapos.
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