Genetic Determinants of CV Disorders Flashcards
Do sarcomeric mutations cause a hypertrophic phenotype, and cytoskeletal mutations cause a dilated phenotype?
Nope. Either can do either.
3 types of primary cardiomyopathy? What’s the end stage for all of them?
Hypertrophic, restrictive, and dilated.
The end stage for all of them is a dilate myopathy.
Mode of inheritance of hypertrophic myopathy?
Autosomal dominant.
Is all hypertrophic cardiomyopathy the same?
Nope… different processes happen depending on the mutated gene… and how that gene is mutated. And there are different severities.
(fairly obvious stuff)
There are systemic syndromes that include cardiomyopathy as an effect.
Yes there are. Such as Noonan syndrome..
What do mutations causing arrhythmogenic right ventricular dysplasia have in common?
They’re all involved in desmosome function.
What kind of myopathy dystrophin-related mutations cause?
Dilated cardiomyopathy.
What do restrictive cardiomyopathies have in common?
Accumulation of some substance.
E.g. hemochromatosis, amyloidosis, glycogen storage diseases, etc.
2 broad processes that might be responsible for most cardiomyopathy?
Ca++ handling.
Energy generation.
Bad consequences of Long QT syndrome?
Prolonged ventricular depolarization predisposes to Torsades des pointes (syncope, seizures, sudden death).
Mode of inheritance of Long QT syndrome?
Depends.
Some are autosomal dominant, some recessive.
What does Brugada syndrome, a variant of long QT syndrome, look like on ECG? (3 things)
Up sloping ST segment, RBBB, T wave inversion.
4 CV features of Marfan’s syndrome?
Aortic root dilation.
Aortic dissection.
Aortic regurgitation.
Mitral regurgitation.
What gene is defective Marfan’s syndrome?
What is its mode of inheritance?
A defect in Fibrillin-1 (FBN1) - an important component of microfibril.
Autosomal dominant -because one bad copy of the gene messes up the microfibril structure, it is dominant.
How does microfibrils being messed up explain the lengthened bones of Marfan’s?
FBN1 normally binds TGF-beta and holds it in an inactive state. If FBN1/microfibrils are messed up, there’s too much TGF-beta signaling -> lengthened limbs.
It’s not a mechanical thing.
