Muscular Dystrophy Flashcards
Why is Duchenne more severe than Becker muscular dystrophy with an early onset and shorter life span?
Complete lack of dystrophin in Duchenne
Reduced amount of dystrophin in Becker
How does lack of dystrophin affect muscle function?
Absence of dystrophin leads to fragility of the myofiber sarcolemma
What is the pathological sequence of events in muscle dystrophy that causes muscle weakness?
Damage to myofiber initiates cycles of fiber degeneration and fiber regeneration, and increased endomysial connective tissue
What kind of dystrophin mutation will cause the greatest pathology?
Small detection but change in reading frame
What one medication has shown proven beneficial and is currently used in treatment of Duchenne?
Prednisone
Why is high intensity aerobic activity and eccentric exercise training contraindicated in children with Duchenne?
Intense exercise causes more damage and thus promotes pathological response in myofiber
What change within the myofiber interferes with transmission of force between adjacent myofiber?
The increased endomysial connective tissue interferes with force transduction
Why is Duchenne not going away?
2/3 new cases are sporadic (no family history)
Why is muscular dystrophy a heterogeneous group of disorders?
Numerous mutations
Mutations cause dystrophy in the ECM, sarcolemma, nuclear envelopes
Can disrupt balance of protein synthesis vs degradation
Numerous and overlapping phenotypes associated with numerous gene loci
How are muscular dystrophies categorized
Phenotypic
Historic
Pathologic (biopsy)
Genetic (genome)
Differentiate different modes of inheritance
Autosomal dominant; one parent can pass the disease, 50% chance of inheritance
Autosomal recessive; both parents are carriers, 25% chance of inheritance
X-Linked (recessive); primarily affects males, pass through carrier moms
Affected
Disease present
Carrier
No disease present, has the gene
Unaffected
No diseases present, no gene
What is the location of dystrophin within the skeletal muscle
Inside the muscle fiber
Sarcolemmal connection
What types of dystrophin mutations can occur
Complete absence
Truncation (decreased size/amount)
Point (disrupts normal production)
De novo mutation
Mutated for the first time, not inherited by parent
Can happen during DNA replication during cell division
Clinical signs and symptoms of Duchenne
Muscle hypertrophy, swinging gait
Symmetric proximal weakness, delayed motor milestones
Cardiac involvement, respiratory complications
Gower’s sign
Difficulty rising from the floor
Sign of Duchenne
How does the muscle change over time in Duchenne?
6-11 years: progressive weakness
11-13 years: loss of ambulation
Why is hypertrophy observed in the calf muscle with Duchenne?
Muscle degeneration is replaced by increased fatty infiltration
How is Becker’s different from Duchenne?
Becker’s has a later onset & ambulation in adulthood
Becker’s is reduced size/amount of dystrophin
