Cardiac

Question 1

What is amyloidosis?

Answer 1

When misfolded amyloid proteins build up in various organs

> 30 types depending on specific protein

Question 2

What gene is associated with transthyretin-related Amyloidosis?

Answer 2

TTR gene (AD)

Question 3

What organs does transthyretin-related Amyloidosis affect?

Answer 3

Peripheral nerves and heart

Question 4

What are the characteristics of the p.Val50Met variant in TTR?

Answer 4

Neuropathy (cardiac involvement is rare)

Disease risk by age 70 between 36-91% depending on ancestry (Portugal highest)

Some heterozygotes remain asymptomatic

Question 5

What are the characteristics of the p.Val42Ile variant in TTR?

Answer 5

~3-3.9% in AA pop
Most het develop late-onset cardiac amyloidosis

Question 6

What are additional maifestations of TTR amyloidosis?

Answer 6

Heart disease
Sensory and/or motor neuropathy
Autonomic dysfunction
Carpal tunnel syndrome
Spinal stenosis
Renal abnormalities
Ocular changes

Question 7

Name three syndromic disorders with DCM…

Answer 7

DMD and Becker

Carvajal syndrome (DSP gene, AR)–woolly hair, palmoplantar keratoderma

Barth syndrome (TAFAZZIN gene, X-linked)–neutropenia, muscle weakness, growth delay, infantile/childhood onset

Question 8

What are the three most common genes associated with DCM?

Answer 8

TTN (~15-20%)
LMNA (~6%)
MYH7 (~4%)

Question 9

What is restrictive cardiomyopathy?

Answer 9

Myocardial stiffness with normal/mildly increased wall thickness

Generally diastolic dysfunction, but normal/mildly reduced EF

Question 10

What is left ventricular noncompaction (LVNC)?

Answer 10

Congenital abnormality of LV
Premature stop in compaction results in thick, spongy trabeculations instead of smooth & firm myocardium

Risk for arrhythmia, thromboembolism, LV dysfunction