Muscular Dystrophy, HCM, Hyperthermia

Question 1

Duchenne muscular dystrophy phenotype

Answer 1

1. abnormal gait
2. gower’s sign
3. calf pseudohypertrophy
4. mild intellectual disability
5. cardiomyopathy
6. 0 reproductive fitness

Question 2

Duchenne muscular dystrophy

molecular defect

Answer 2

Dystrophin (DMD) gene mutation by:

1. lg deletions or
2. frameshifts

Normally, dystrophin links the cytoskeleton with the extracellular matrix.

Question 3

Duchenne muscular dystrophy

mode of inheritance

Answer 3

X-linked recessive

Question 4

Diagnosing Duchenne muscular dystrophy

Answer 4

Serum creatine kinase (w/o muscle biopsy)

Gower maneuver

Question 5

How is Becker muscular dystrophy different from DMD?

Answer 5

BMD is due to smaller in-frame deletions

• more mild than DMD
• Still has high creatine kinase
• later-onset cardiomyopathy than DMD

Question 6

Duchenne muscular dystrophy

treatment

Answer 6

Corticosteroids: prolong independent ambulation

many others

Question 7

Role of manipulation of myostatin function in the treatment of muscular dystrophies

Answer 7

Myostatin is a growth regulator (inhibitor)
Regulates muscle mass by acting as negative feedback mech.

Possibly used to combat cardiomyopathy which makes heart (dilated, hypertrophic and restrictive)

Question 8

Familial hypertrophic cardiac myopathy (FHC / familial HCM)

• mode of inheritance
• main mutation type?

Answer 8

AD

Mostly missense mut.
»> causes a mutation in cardiac myosin heavy chain where it interacts with actin and ATP

Question 9

Familial hypertrophic cardiac myopathy (FHC / familial HCM) genetic characteristics

Answer 9

Shows:

1. genetic heterogeneity: single phenotype caused by mult mutations
2. incomplete Penetrance: they express disease it or they dont even though they have bad gene

Question 10

Hypertrophic cardiac myopathy (HCM) phenotype

Answer 10

1. Cardiomyocyte and cardiac hypertrophy.
2. Myocyte disarray (compromised function.)
3. Interstitial and replacement fibrosis (arrhythmia)
4. Dysplastic arterioles (ischemia)

Question 11

Malignant hyperthermia

• mode of inhertance
• mutation in which gene?

Answer 11

Dominant mode of inheritance

Mutation in RYR1 –> mut. RYR Ca2+ release channel in SR

Question 12

What triggers malignant hyperthermia?

Answer 12

> > inhaling HALOTHANE or SUCCINYLCHOLINE anesthetics (like during breast surgery)

Question 13

Describe physiological process that results in malignant hyperthermia

Answer 13

The anesthetics trigger inappropriate release of Ca2+

Meanwhile, Ca2+ still leaks out from SR

> > ATPase pumps Ca2+ back into SR in futile attempt.
–»heat is generated to lethal level (hyperthermia)

1. tons of muscle simultaneously contracts
   (muscle rigidity/muscle spasm)
2. Increase CO2 production
3. Rhabdomyolysis

Question 14

What is used to treat malignant hyperthermia?

what does it do?

Answer 14

Dantrolene:

blocks muscle contraction by blocking Ca2+ release from SR

Question 15

Just for funsies, what is Pleiotropy? Phenotypic heterogeneity? Allelic heterogeneity?

Answer 15

Pleiotropy: (disco ball) single gene mutation –> mult. Phenotypes

Phenotypic heterogeneity: mut in same gene –> diff phenotype

Allelic heterogeneity: mult mut in same gene –> similar phenotype
(Very similar/same as genetic heterogeneity (not sure)