Muscular Dystrophies

Question 1

What is muscular dystrophy?

Answer 1

inherited group of myopathic disorders

genetic defects impair normal muscle func.
-characterized by progressive muscle weakness and wasting

Question 2

Besides muscle weakness and wasting, what else can be seen in muscular dystrophy?

Answer 2

muscle contractures

impairment of respiratory func.

skeletal deformities

cardiac involvement

Question 3

What are the most common types of muscular dystrophies?

Answer 3

Duchenne Muscle Dystrophy

Becker muscular dystrophy

Question 4

Etiology of DMD?

Answer 4

2/3 inherited mutation on X chromosome

1/3 spontaneous mutation

Question 5

Etiology of BMD?

Answer 5

almost all inherited from mom carrying genetic mutation on X chromosome

Question 6

Epidemiology of muscular dystrophy?

Answer 6

very rare for females to develop DMD or BMD

Question 7

Pathophys of DMD and BMD

Answer 7

both have genetic mutation on X chromosome Xp21 position

DMD: LOSS of func. expression, affected gene codes for the protein dystrophin > dystrophin levels reduced or absent

BMD: REDUCED func. expression, affected gene codes for dystrophin > dystrophin levels are generally normal but the protein is altered

Question 8

What occurs as a result of the genetic mutation?

Answer 8

ongoing degeneration and regeneration of muscle fibers

progressive breakdown of affected skeletal muscle
-can have muscle pseudohypertrophy and later atrophy

Question 9

Clinical manifestations of DMD?

Answer 9

growth delay in first yr of life

cognitive impairment

muscle involvement
-weakness begins at 2-3 y/o

Question 10

What muscles are typically affected first in DMD?

Answer 10

proximal before distal

LE before UE

Question 11

Gait in pt with DMD?

Answer 11

waddling gait develops btwn 12-15

Gower’s sign: may use hand support when arising from ground

Question 12

pulmonary abn in DMD?

Answer 12

impaired res func > need ventilator support by ~25

Scoliosis > decreased CW compliance

Gradual weakening of res muscles

Question 13

What cardiac abn. may occur with DMD?

Answer 13

primary dilated cardiomyopathy

conduction abnormalities

usually around teenage yrs

Question 14

What sxs can occur late in DMD disease progression?

Answer 14

urinary and bowel incontinence

Question 15

Clinical manifestation of BMD?

Answer 15

Muscle involvement onset 5-15 yrs, milder and slower progression, need for ambulatory support occurs much later and wheelchair dependence is rare

CARDIAC involvement is often the predominant feature

growth delay and cognitive impairment UNCOMMON

Question 16

When should you suspect muscular dystrophy?

Answer 16

any evidence of delayed motor milestones in young child with +fam hx

child not walking by 16-18 mos or presence of Gower’s sign, toe walking or calf hypertrophy

unexplained elevated transaminase levels

Question 17

Why would transaminase levels be elevated in muscular dystrophy?

Answer 17

due to muscle inflammation and breakdown which must be metabolized by the body > puts extra stress on liver

Question 18

Dx studies?

Answer 18

CK

Genetic testing for Xp21 gene mutation

EMG

Muscle biopsy

Dilated cardiomyopathy work up: Echo, ECG

Spirometry: res func

Question 19

What would be positive findings on muscle biopsy?

Answer 19

DMD: absence of dystrophin

BMD: diminished quantity or quality of dystrophin

Question 20

Tx for muscular dystrophy?

Answer 20

Prednisone 0.75mg daily or every other day
-can delay wheelchair dependence by 3 yrs

PT

psychological support

surg for muscle contractures & scoliosis

Ambulatory support

Cardioprotective meds

Ventilatory support > almost all DMD will need