Genetics

Question 1

What is penetrance?

Answer 1

The likelihood of having a disease if you have a gene mutation
100% penetrance means you will always get the disease if you have the mutation

Question 2

What can an exonic mutation result in?

Answer 2

Change of amino acid sequence
Create stop codon
Frameshift
No effect

Question 3

Are intronic variants commonly pathogenic?

Answer 3

No

Question 4

In describing mutations, how is a stop codon symbolised?

Answer 4

*

Question 5

What is the cDNA?

Answer 5

Mature mRNA sequence with the introns removed, referenced to the first base of the first codon

Question 6

What mutation results in marfan syndrome?

Answer 6

Fibrillin mutation

Question 7

What causes Loeys dietz Syndrome and what are some classical features?

Answer 7

Mutation sin TBR1 or TBR2
Bifid uvula
Widely spaced eyes
Tortuous blood vessels

Question 8

What mutations result in romano-ward (AD) syndrome?

Answer 8

LQTS mutations

Question 9

How is familial hypercholesterolemia diagnosed?

Answer 9

Total cholesterol >7.5 mmol/L or LDL cholesterol >4.9 mmol/L in adults
Tendon xanthomas
DNA based evidence of a mutation in LDLR, APOB or PCSK9
FMHx of premature MI (<50 yrs)
FMHx of elevated total cholesterol >7.5 mmol/L

Question 10

What are the incidences of “rare” genetic cardiac disease?

Answer 10

Marfans; 1 in 5000
Long QT; 1 in 2000
HOCM 1 in 500
Familial hypercholesterolemia 1 in 500

Question 11

What are the common channelopathies that can lead to sudden death?

Answer 11

Long QT syndrome
Brugada Syndrome
Short QT syndrome
Catecholaminergic polymorphic ventricular tachycardia

Question 12

Describe catecholaminergic polymorphic ventricular tachycardia (CPVT)?

Answer 12

AD mutation in gene encoding for cardiac ryanodine receptor (RYR2) the main intracellular calcium release channel of cardiomyocytes

Question 13

What are the ECG findings of brugada syndrome?

Answer 13

RBBB
Persistent ST elevation in leads V1-3
Normal QT intervals

Question 14

What is the genetics behind brugada syndrome?

Answer 14

Mutation of cardiac sodium channel SCN5A

AD

Question 15

What drugs should be avoided in brugada syndrome?

Answer 15

Antiarrhythmic drugs - specifically class 1
Psychotropic drugs, TCA, lithium, antipsychotics,
Anaesthetics/ analgesics; bupivacaine, procaine, propofol
Excessive alcohol
Cannabis
Cocaine

Question 16

What is the danger with long QT syndrome?

Answer 16

Prolonged QT intervals and/or polymorphic U waves are assoc with torsades de pointes and subsequent deterioration to VF

Question 17

What investigations are recommended for screening for inherited cardiac issues?

Answer 17

12 lead ECG
Echo
Holter monitor
Cardio-pulmonary exercise ECG test

Question 18

What is the most common genetic cardiac disease?

Answer 18

HOCM

Question 19

What are the characteristics and diagnostic features of HOCM?

Answer 19

Marked and asymmetric left ventricular hypertrophy
Left ventricular outflow obstruction at rest caused by mitral-septal contact during systole
LV wall thickness >13mm

Question 20

What are symptoms of HOCM?

Answer 20

Chest pain
Dyspnoea
Palpitations
Syncope

Question 21

What are the treatments available for HOCM?

Answer 21

ICD
Beta blockers, verapamil
Surgical myectomy

Question 22

What are the genetic features of HOCM?

Answer 22

AD with incomplete penetrance
4 loci;
Beta myosin heavy chain on chromosome 14 (30%)
Alpha-tropomyosin on chromosome 15 (3%)
Cardiac troponin T on chromosome 1 (15%)
Locus on chromosome 11

Question 23

Can you give digoxin in AF with co-existing HOCM?

Answer 23

No

Question 24

Describe arrhythmogenic right ventricular cardiomyopathy

Answer 24

Rare cause of dilated cardiomyopathy in which there is gradual replacement of the myocardium of RV with fibroadipose tissue

Question 25

What can cause dilated cardiomyopathy?

Answer 25

Familial 
Coronary artery disease 
Valvular heart disease 
Hypothyroidism 
Thyrotoxicosis 
Haemochromatosis 
Collagen vascular disorders 
Alcohol or drug related heart muscle disease

Question 26

What are the ecg changes seen in RBBB?

Answer 26

Best seen in V1 with an rSr pattern 
QRS duration >120 ms 
Dominant R in V1
Inverted T waves in V1-3 or V4 
Wide and deep S in V6

Question 27

What are the ecg changes seen in LBBB?

Answer 27

Q wave in V1 and an R wave in V6
Best seen in V6 with an M pattern
Deep and wide S wave in V1