MSKS Pathology Lecture 4_Myopathies & Dystrophies Flashcards
What is the Pathogenesis of polymyositis
Ther is an increased expression of MHC class I molecules on myofibers and endomysial inflammatory infiltrates containing CD8+ cytotoxic T cells. The T cells lead auto immunity and subsequent myofiber necrosis and then regeneration
Who is most at risk for Inclusion Body Myositis?
Elderly people, infact this is the most common inflammatory myopathy in patients older than 60
How does Dermatomyositis manifest differently in children and adults
In children it is typically an isolated condition. In adults it manifests as a paraneoplastic disorder (caused by cancer)
What causes Mitochondrial myopathies, what is the inheritance pattern, and when/how does it manifest?
๏ Can stem from mutations in either the mitochondrial or nuclear genomes because both
encode proteins and RNAs that are critical for mitochondrial function.
๏ The variants caused by mitochondrial mutations show maternal inheritance.
๏ Mitochondrial myopathies usually manifest in early adulthood with proximal muscle
weakness and sometimes with severe involvement of the ocular musculature.
What is the main clinical manifestation and inheritance pattern of Myotonic Dystrophy
The main clinical manifestation of myotonic dystrophy is sustained involuntary muscle contractions (like not being able to relax grip after a hand shake)
It is inherited as an autosomal dominant trait
What are Myopathies due to Inborn Errors of Metabolism
Include disorders of glycogen synthesis and degradation and lipid handling.
What do Limb-Girdle Muscular dystrophies effect and what are their genetic basis?
๏ These muscular dystrophies preferentially affect the proximal musculature of the trunk and limbs.
๏ Their genetic basis is heterogeneous.
What kind of mutation is typically found in patients with BMD
They typically have a point mutation. This leads to dystophin with reduced activity. This is the reason BMD is less sever than DMD
What causes the most common muscular
dystrophies and what are their inheritance patterns?
They are caused by disruption in dystrophin (the protein that binds periferal actin to integrins) and they are typically xlinked (only show up in boys). They are often reffered to as dystrophinopathies
What are the clinical features of Dermatomyositis?
๏ It typically affects the proximal muscles first (tasks such as getting up from a chair and climbing steps become increasingly difficult).
๏ Fine movements controlled by distal muscles are affected only late in the disease.
๏ Associated myopathic changes on electrophysiologic studies and elevation in serum creatine kinase levels are reflectiveof muscle damage.
๏ Various rashes including lilac colored discoloration of the upper eyelids and scaling erythematous eruption or dusky red patches over the knuckles, elbows, and knees (Gottron papules)
What is polymyositis?
Polymyositis is an adult-onset inflammatory myopathy that shares myalgia and weakness with dermatomyositis but lacks its distinctive cutaneous features
What kind of mutation is typically found in a Patient with DMD
They typically have a frame shift mutation in the dystrophin gene. This often leads to no dystrophin production
What is the main mechanisium of Primary muscle diseases
They are often associated with segmental necrosis and
regeneration of individual muscle fibers.
How are Congenital myopathies defined?
typically present in infancy with muscle defects that
tend to be static or to even improve with time.
What are the three lines of defence against inflamatory myopathies (dermatomyositis and polymyositis)?
1) Corticosteroids
2) Immunosuppressive drugs like azathioprine and methotrexate.
3) Intravenous immunoglobulin (IVIG), cyclophosphamide, cyclosporine, and rituximab
All of these drugs seek to suppress the immune system
What are 5 clinical signs of Mitochondrial myopathies
lactic acidosis, endocrinopathy, peripheral neuropathy, cardiomyopathy, and aggregates of abnormal mitochondria (ragged red fibers)
What is Emery-Dreifuss Muscular Dystrophy (EMD)
A genetically heterogeneous disorder caused by mutations affecting structural proteins found in the nucleus.
What are the 4 clinical features of DMD?
๏ Often the first symptoms of DMD are clumsiness and
an inability to keep up with peers because of muscle
weakness.
๏ The weakness typically begins in the pelvic girdle and
next involves the shoulder girdle.
๏ Enlargement of the calves, pseudohypertrophy, is an
early physical finding.
-high serum creatine kinase levels are
present at birth and persist through the first decade of life
What is the pathogenesis of Dystrophinopathies?
1) Dystrophin-glycoprotein complex defects are
thought to make muscle cells vulnerable to
membrane tears during contraction
2) Muscle damage out paces capacity for repair
3) Because dystrophin is essential in cardiac muscel, this will eventually lead to cardio myopathy and be fatal
What is Facioscapulohumeral Dystrophy
An autosomal dominant form of muscular dystrophy that is caused by complex genetic changes that allow expression of the transcription factor DUX4 that is normally repressed in mature tissues.
What are Ion channel myopathies
๏ A group of familial disorders caused by inherited defects in ion channels that are characterized by myotonia, relapsing episodes of hypotonic paralysis associated with abnormal serum potassium levels, or both.
What is the morphologic hallmark of inclusion body myositis?
the presence of rimmed vacuoles that contain aggregates of the same proteins that accumulate in the brains of patients with neurodegenerative diseases
What are the two most common muscular dystrophies?
Duchenne muscular dystrophy (DMD) and
Becker muscular dystrophy (BMD)
How are muscular distrophies defined?
They are associated with progressive muscle injury in
patients who have normal muscle function at birth.
What is the pathological basis for dermatomyositis
It is believed to be an autoimmune disorder and it manifest with type 1 interferon induced
products being strongly upregulated in affected muscles
