Neuromuscular Conditions

Question 1

what is the role of the dystroglycoprotein (DGC) complex?

Answer 1

it serves as the link between cytoskeleton and extracellular matrix

Question 2

What do muscle biopsies show in muscular dystrophies?

Answer 2

fiber size variation, myonecrosis, muscle replacement with increased amounts of fat and connective tissue

Question 3

What is the most common pediatric muscular dystrophy?

Answer 3

Duchenne muscular dystrophy (DMD)

Question 4

What is the inheritance pattern of Duchenne and Becker muscular dystrophies?

Answer 4

X-linked recessive

Question 5

What genetic mutation causes Duchenne and Becker muscular dysrophies?

Answer 5

mutations in the DMD gene at loci Xp21 on the X chromosome

Question 6

The DMD gene codes for which protein?

Answer 6

dystrophin protein

Question 7

How many exons are there in the DMD gene?

Answer 7

79 exons

Question 8

What are the hallmark features of DMD?

Answer 8

progressive muscle weakness and calf pseudohypertrophy

Question 9

Which motor function is usually impacted in the pre-symptomatic period of DMD?

Answer 9

neck flexion weakness - head lag is notable on physical exam even after good head control has been developmentally achieved

Question 10

Which lab abnormalities suggest myopathic etiologies vs. hepatic?

Answer 10

elevated AST/ALT, elevated CK, with normal GGT (which is not present in muscle)

Question 11

What common cognitive effects are seen in DMD?

Answer 11

mean IQ of approx 1.0 standard deviation below peers; concomitant diagnosis of autism spectrum disorder is 21% more likely in DMD than the general population

Question 12

What are useful predictors for when a DMD boy will lose ambulation?

Answer 12

timed motor performances:
- a 30-meter decline in the 6 min walk test predicts loss of ambulation in the next year
- Decline > 10% on the 10meter walk/run test over the course of a year is predictive of loss of ambulation over the next 4 years

Question 13

What is the average age of full-time wheelchair use in DMD patients NOT treated with steroids?

Answer 13

10 years +/- 3 years

Question 14

Approximately how long does glucocorticoid treatment delay wheelchair use in DMD populations?

Answer 14

Delays transition to wheelchair by approx 1-2 years

Question 15

What are the causes of ultimate mortality in DMD kids?

Answer 15

respiratory failure and cardiac failure (conduction abnormalities, dilated cardiomyopathy)

Question 16

Median survival in DMD?

Answer 16

24-26 years

Question 17

Median survival in Becker muscular dystrophy?

Answer 17

67 years

Question 18

Clinical differentiation between Becker and DMD?

Answer 18

Becker has same pattern of muscle weakness, but later onset and slower rate of progression (usually remain ambulatory > 16yo)