muscular dystrophy

Question 1

muscular dystrophy phenotype

Answer 1

asymptomatic throughout life, some have dyspnea, angina, and syncope, some experience sudden cardiac death, and some of those die suddenly (enriched in athletes), mortality <1% per person/year

Question 2

clinical presentations

Answer 2

cardiac murmur (if LV outflow obstruction), Cardiac ‘Pump’ Failure (dyspnea, angina), Arrhythmia (syncope/sudden death), Sports/Family screening

Question 3

Diagnosis

Answer 3

Echocardiogram, EKG, MRI, Family history, Genetic testing, Chest X-ray

Question 4

Molecular defect

Answer 4

Autosomal dominant incomplete penetrance in structural protein genes - often missense

Question 5

Malignant Hyperthermia

Answer 5

hypermetabolism, skeletal muscle damage, hyperthermia, death if untreated, 70% have dominant RYR2 mutation, or exposure to anesthesia (halothane and succinylcholine)

Question 6

how malignant hyperthermia works

Answer 6

Ryanodine triggered by anesthetics, releases lots of Ca, stays open. => muscle contraction, generates heat and CO2. Muscles can’t relax, use all ATP, leads to phenotypes

Question 7

Duchenne Muscular Dystrophy

Answer 7

X-linked disease, 1:3500 males, Dystrophin (DMD) mutation , in boys: onset of skeletal muscle disease, abnormal gait, Gowers’ sign, Calf pseudohypertrophy, high creatinine kinase (1000s), mild intellectual disability, wheelchair bound by age 11, death in 20s (cardiopulmonary), cardiomyopathy 100% by 18 yrs, reproductive fitness ~0

Question 8

DMD defect

Answer 8

Dystrophin; intracellular protein, Expressed in skeletal, smooth, and cardiac muscle, Sarcolemma associated complex (skeletal, stabilizes the sarcolemma), 60-65% large deletions, 5-10% large duplications, 15-30% small dup/dels, nucleotide changes

Question 9

manipulation of myostatin function

Answer 9

if we could inhibit myostatin, those is MD could lose less muscle mass