HRR: genetics of heart failure Flashcards
What factors limit detection of familial cardiomyopathies?
De novo mutations, age-dependent phenotypes, incomplete penetrance, incomplete pedigrees.
What are the heritable cardiomyopathies?
Hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, and right ventricular cardiomyopathy.
What is the inheritance of hypertrophic cardiomyopathy?
Autosomal dominant.
What is the general definition of hypertrophic cardiomyopathy?
A greater than normal wall thickness in the absence of increased external load.
What component is mutated in hypertrophic cardiomyopathy?
The sarcomere.
What genes are associated with hypertrophic cardiomyopathy?
MYH7 and MYBPC3.
What type of diseases can mimic hypertrophic cardiomyopathy?
Glycogen storage diseases.
What are symptoms of Fabry disease? What is it associated with?
Angiokeratomas of skin, corneal clouding, renal insufficiency. Associated with HCM.
What is the inheritance pattern of nonischemic dilated cardiomyopathy?
Autosomal dominant.
What are the criteria for familial dilated cardiomyopathy?
- Two or more individuals in one family have unexplained DCM. 2. First degree relative with idiopathic DCM had unexplained sudden death before 35. 3. No other cause for DCM found.
What genes are associated with ion channel abnormalities in dilated cardiomyopathy?
ABCC9 and SCN5A.
What kind of mutations cause dilated cardiomyopathy?
Cytoskeletal, sarcomere, ion channels, nuclear envelope, transcription factors.
what are the categories of genes associated with DCM
- cytoskeletal
- sarcomere
- nuclear envelope
- ion channels
- cardiac transcription factors
Brugada syndrome/long QT can be associated with?
Dilated cardiomyopathy.
What are common cytoskeletal mutations in dilated cardiomyopathy?
Dystrophin, titin.
Describe restrictive cardiomyopathy.
LV wall thickness and EF are nearly normal, but stiffness results in low output, atrial dilation, and heart failure.
What is the inheritance pattern of restrictive cardiomyopathy?
Recessive.
Mutation in what gene is associated with restrictive cardiomyopathy?
TTR
Mutations in which sarcomere genes are associated with restrictive cardiomyopathy?
TNNI3, TNNT2, ACTC, MYH7.
Mutations in what non-sarcomere genes are associated with restrictive cardiomyopathy?
LMNA (lamin A/C), DES (desmin), TTR (transthyretin).
What is familial amyloidosis?
Abnormal deposition of misfolded protein in the heart, nerves, kidneys, lungs.
What is arrhythmogenic right ventricular cardiomyopathy?
Fibrofatty replacement of myocytes in the right ventricle, usually resulting in ventricular arrhythmia.
A patient presents with arrhythmia and a patchy ventricular scar. What do they have?
Arrhythmogenic right ventricular cardiomyopathy.
Mutations in ___ cause arrhythmogenic right ventricular cardiomyopathy, specifically?
Desmosomes; PKP2.
