The Muscular Dystrophies

Question 1

Def of muscular dystrophies

Answer 1

Inherited caused by progressive weakness and degeneration of skeletal muscles

Question 2

CLassidication of MD

Answer 2

By clinical presentation, mode of inheritance, age of onset and progression

Question 3

Dystrophin role
What happens without it
Gene stuff

Answer 3

Protein that localizes to cytoplasmic surface of plasma membrane of muscle fibers…acts as link between EC matrix outside fiber and cytoskeleton inside

Withoutr it, sarcolemema is fragile and cannot withstand stressed…get increase IC Ca which activates proteases resulting in death

Overtime, regen capcity becomes insuff to replace lost fibers and necrotic fibers replaced by fat and CT…results in psueohypertrophy in legs

DMD has large gene size

Question 4

DMD genetics, inheritance, progression

Answer 4

Mutations (most deletions) in DMD
X-linked…most female are asymptomatic with maybe weakness or cardiomyopathy

Progressive wasting of skeletal muscles
3-5…motor delay, gait, difficulty rising from ground, falls, weakness of limb-irlde muscles (prox lower limb and truncal - gower sign)

8-12…contractures of calf muscles, lordosis of spine, can’t walk

20-30 - cardiac./resp impair leads to death

Question 5

Diagnosis and managment of DMD

Corticosteroid and genetic managment

Answer 5

Serum muscle enzymes - serum CK levels are often 10-20 times limit before 5
Genetic testing - DMD
Muscle biopsy - can quantify dystrophin and assess size

Corticosteroid - prednisone…monitor for weight gain

Genetic counseling…prenatal diagnosis available and periodic CV screening of carrier feamles recommend ed

Question 6

NM managment
Ortho

for DMD

Answer 6

Give live vaccines before starting steroids…encourage submax aerobic exercise but limit high resistance ST

Try to maintain ambulation as long as possible…stretch and use night splints…spinal radiographs…consider soinal fusion if impacted resp capacity

Question 7

Resp and cardiac managment of DMD

Answer 7

Pulm function tests sregularly…tx sleep apnea…teach airwya clearance methiods…tx acute resp infections early

Monitor EKG and ECG…dilated cardiomyopathy and arrythmias common

Question 8

Nutrition and pscyhosocial mamagment DMD

Answer 8

Osteoporosis with bone density scanes…supplement calcium and Vit D…some boys need bisphos therapy…monitor dysphagia and WL

Monitor behav issues with steroid use…cog impairment common

Question 9

BMD pathology, onset, presentation, life

Answer 9

DMD that maintains open reading frame but get partially functional dystrophin…more dystrophin=less severe

5-15 years old

Presentation similar but milder, more variable, and slower

No contractures, severe scoliosis and may life to adulthood

Question 10

Myotonic dystrophygenetics and cliincial

Answer 10

Most common in adults
AD
Type 1 - DMPK, Type 2 - ANF9

Number of repeats increases from one generation to next

Myotonia (hyperexcitability of skeletal muscles), muscle weakness, cardiac conduction defects, pain, peripheral neurpp[ahy, frontal balding, temporal wasitng, cataracts, and endocrine…presents in young adults