MD - Myopathies

Question 1

Most common of childhood mm diseases

Answer 1

MD
Genetic origin
Progressive mm wasting, weakness, disability

Question 2

Types of MD

Answer 2

Duchenne (pseudohypertrophic)
Becker
Facioscapulohumeral
Limb Girdle
Oculopharyngeal

Question 3

Epidemiology

Answer 3

Only in boys
Typically identified by around age 3.
1/3500 male births

Question 4

Prognosis

Answer 4

Death usually by late teens
25% live to 21 years
Death usually due to cardiac/pulmonary effects
DMD is the most common fatal childhood genetic disorder.

Question 5

DMD - caused by

Answer 5

Absence of the protein dystrophin

Question 6

Pathophys - MD

Answer 6

Gene on X chromosome is defective
Dystrophin gene is one of the largest known human genes.
Codes for many different proteins, including dystrophin

Question 7

What is dystrophin

Answer 7

Dystrophin is a filamentous cytoskeletal protein

Binds actin and sarcolemmal cytoskeleton to basement membrane via Dystrophin Glycoprotein Complex (DGC)

Question 8

Lack of dystrophin — means what

Answer 8

No DGC

Question 9

Dystrophin is present where

Answer 9

Skeletal, cardiac, and smooth mm

Question 10

Dystrophin functions

Answer 10

exact function in healthy muscle and the mechanism(s) of effect associated with dystrophic muscle are still unclear.
Structural and Cell Signaling

Question 11

Dystrophin functions - Structural

Answer 11

force transmission from sarcomeres to extracellular connective tissue.
Dec DGC leads to force transmission causing structural damage

Question 12

Dystrophin functions - cell signaling

Answer 12

nNOS – NO production increases skeletal muscle blood flow
Dec NO leads to ischemic injury
Ion channel function

Question 13

DMD - fibers become damaged when

Answer 13

Producing force
Sarcolemma damage leads to Ca infiltration and then tissue destruction via Ca activated proteinases
Elevated serum levels of mm proteins (CPK)
Poor tolerance of eccentric contractions

Question 14

DMD - repeated cycles of

Answer 14

Degeneration and regeneration over time
Net degeneration over time; replaced by fat and connective tissue
Muscle nucleii become centralized.
Variation in fiber size

Question 15

DMD - Clinical Manifestations - initial effects where

Answer 15

Pelvic girdle

Weakness - waddling gait

Question 16

DMD - Clinical manifestations

Answer 16

Gower sign (weak glutes and low back)
Toe walking (weak DF)
Contractures

Question 17

DMD - Clinical manifestations - Pulmonary

Answer 17

Kyphoscoliosis: humped upper spine + scoliosis
Deterioration of pulmonary musculature
Effects accelerate with eventual wheelchair use.

Question 18

DMD - Clinical manifestations - Cardiac

Answer 18

50% heart failure

95% some cardiac involvement

Question 19

DMD - Clinical manifestations - GI

Answer 19

constipation

gastric dilation

Question 20

DMD - Clinical manifestations - Intellectual

Answer 20

80% have some intellectual disability
Mean IQ = 80
Dystrophin present in brain tissue

Question 21

DMD - Clinical manifestations - Pseudohypertrophy

Answer 21

Connective tissue and fat replace muscle tissue

Question 22

DMD - medical management

Answer 22

No cure

Goal is to maintain mm function or as long as possible

Question 23

DMD - medical management - exercise

Answer 23

Mild exercise helps maintain muscle
Aquatic exercise – concentric only
Hard exercise may exacerbate muscle damage, especially with eccentric contractions.

Question 24

DMD - medical management - meds

Answer 24

Anti inflammatory drugs
Prednisone - inc strength, dec rate of disease progression
Deflazacort - less side effects

Question 25

Becker MD

Answer 25

Milder/slower form of DMD

Question 26

Becker MD - genetic

Answer 26

Genetic error alters dystrophin

Dystrophin works, but is less effective than normal.

Question 27

Becker rate

Answer 27

10% of Duchenne

Question 28

Becker - clinical symptoms

Answer 28

Occur later

Between ages 5 and 15

Question 29

Becker - pattern of weakness across mm groups

Answer 29

similar to DMD

Question 30

Becker - lifespan

Answer 30

often into middle age

Question 31

Becker - care

Answer 31

Maintain ambulation

Monitor CP system

Question 32

Fascioscapulohumeral MD - weakness where

Answer 32

Facial and shoulder girdle mm
Expressionless face
Shoulder drooping

Question 33

Fascioscapulohumeral MD - protein defect

Answer 33

not well understood

we just know it involves Chromosome 4

Question 34

Fascioscapulohumeral MD - when does it start

Answer 34

May begin in childhood or as adult

Can occur in F

Question 35

Fascioscapulohumeral MD - progression

Answer 35

Slow

Normal life expectancy

Question 36

Fascioscapulohumeral MD - PT

Answer 36

Prevent contractures
Maintain ambulation
Keep mobility

Question 37

Scapuloperoneal MD

Answer 37

Variant of fascioscapulohumeral
Initially present with footdrop and shoulder weakness.
Normal life expectancy.

Question 38

Scapuloperoneal MD - PT

Answer 38

maintain ambulation and function; AFOs for foot drop

Question 39

Limb girdle MD -

Answer 39

Two Categories
Defects in various proteins of the sarcoglycans (affiliated with DGC) in sarcolemma.
Defect in enzyme associated with Ca++-activated proteinase.
Umbrella term for many different variants.

Question 40

Limb girdle MD - initially present with

Answer 40

Shoulder and pelvic girdle weakness

Question 41

Limb girdle MD - Prevalence

Answer 41

1/50,000

Question 42

Limb girdle MD - PT

Answer 42

For ambulation and function

Monitor for CP effects