HRR: genetics of heart failure

Question 1

What factors limit detection of familial cardiomyopathies?

Answer 1

De novo mutations, age-dependent phenotypes, incomplete penetrance, incomplete pedigrees.

Question 2

What are the heritable cardiomyopathies?

Answer 2

Hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, and right ventricular cardiomyopathy.

Question 3

What is the inheritance of hypertrophic cardiomyopathy?

Answer 3

Autosomal dominant.

Question 4

What is the general definition of hypertrophic cardiomyopathy?

Answer 4

A greater than normal wall thickness in the absence of increased external load.

Question 5

What component is mutated in hypertrophic cardiomyopathy?

Answer 5

The sarcomere.

Question 6

What genes are associated with hypertrophic cardiomyopathy?

Answer 6

MYH7 and MYBPC3.

Question 7

What type of diseases can mimic hypertrophic cardiomyopathy?

Answer 7

Glycogen storage diseases.

Question 8

What are symptoms of Fabry disease? What is it associated with?

Answer 8

Angiokeratomas of skin, corneal clouding, renal insufficiency. Associated with HCM.

Question 9

What is the inheritance pattern of nonischemic dilated cardiomyopathy?

Answer 9

Autosomal dominant.

Question 10

What are the criteria for familial dilated cardiomyopathy?

Answer 10

1. 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.

Question 11

What genes are associated with ion channel abnormalities in dilated cardiomyopathy?

Answer 11

ABCC9 and SCN5A.

Question 12

What kind of mutations cause dilated cardiomyopathy?

Answer 12

Cytoskeletal, sarcomere, ion channels, nuclear envelope, transcription factors.

Question 13

what are the categories of genes associated with DCM

Answer 13

1. cytoskeletal
2. sarcomere
3. nuclear envelope
4. ion channels
5. cardiac transcription factors

Question 14

Brugada syndrome/long QT can be associated with?

Answer 14

Dilated cardiomyopathy.

Question 15

What are common cytoskeletal mutations in dilated cardiomyopathy?

Answer 15

Dystrophin, titin.

Question 16

Describe restrictive cardiomyopathy.

Answer 16

LV wall thickness and EF are nearly normal, but stiffness results in low output, atrial dilation, and heart failure.

Question 17

What is the inheritance pattern of restrictive cardiomyopathy?

Answer 17

Recessive.

Question 18

Mutation in what gene is associated with restrictive cardiomyopathy?

Answer 18

TTR

Question 19

Mutations in which sarcomere genes are associated with restrictive cardiomyopathy?

Answer 19

TNNI3, TNNT2, ACTC, MYH7.

Question 20

Mutations in what non-sarcomere genes are associated with restrictive cardiomyopathy?

Answer 20

LMNA (lamin A/C), DES (desmin), TTR (transthyretin).

Question 21

What is familial amyloidosis?

Answer 21

Abnormal deposition of misfolded protein in the heart, nerves, kidneys, lungs.

Question 22

What is arrhythmogenic right ventricular cardiomyopathy?

Answer 22

Fibrofatty replacement of myocytes in the right ventricle, usually resulting in ventricular arrhythmia.

Question 23

A patient presents with arrhythmia and a patchy ventricular scar. What do they have?

Answer 23

Arrhythmogenic right ventricular cardiomyopathy.

Question 24

Mutations in ___ cause arrhythmogenic right ventricular cardiomyopathy, specifically?

Answer 24

Desmosomes; PKP2.