Genetics and Cardiovascular Disease

Question 1

What changes can occur in genetic code, resulting in cardiovascular issues?

Answer 1

Chromosomal disorders
Microdeletions
Single-gene disorders
Teratogens
Multifactorial

Question 2

What are some chromosomal/genetic disorders that result in cardiovascular problems?

Answer 2

Turner Syndrome
- coarctation of aorta

Down’s Syndrome
- AV septal defects

Noonan syndrome
- Pulmonary stenosis

Costello Syndrome
- cardiomyopathy

22q11 Deletion Syndrome

• cardiac malformation
• ‘CATCH22’
• (cardiac, abnormal facies, thymic hypoplasia, cleft palate, hypoparathyroidism, 22q11 deletion)

Williams Syndrome
- aortic stenosis

Question 3

What are some genetic cardiac diseases?

Answer 3

Cardiovascular connective tissue diseases

• Marfan
• Loeys-Dietz
• Ehlers Danlos
• Familial Thoracic Aortic Aneurysm

Familial Arrhythmias

• Long QT
• Brugada
• Catecholaminergic polymorphic ventricular tachycardia
• Arrhythmogenic right ventricular cardiomyopathy

Familail Cardiomyopathy

• Hypertrophic Cardiomyopathy
• Dilated Cardiomyopathy

Question 4

What is Marfan’s Syndrome?

Answer 4

Autosomal Dominant Condition
Multisystem
Connective Tissue
- Fibrillin 1 gene

Question 5

What is the clinical criteria for diagnosis of Marfan’s?

Answer 5

Aortic dilatation/dissection
Ectopia lentin
Systemic score >7
- skeletal
- skin
- respiratory
- dural ectasia
- mitral valve prolapse
- myopia

Family History
Fibrillin 1 mutation

2 system findings must be positive

Question 6

What additional tests might be done in Marfan’s?

Answer 6

Echo mandatory

Dural ectasia affects 92% of Marfan’s patients
Protrusio affects 47%
- do MRI and/or Pelvic X-ray where diagnosis would change if positive

Question 7

When should you do a genetic test in suspected Marfan’s?

Answer 7

When a positive result would change the diagnosis

79% fulfil Ghent criteria without mutation result

Question 8

What is the optimal management of Marfan’s?

Answer 8

Annual (at least) review
Echo
Beta blockers
ARB
Prophylactic surgery if sinus of valsalva exceeds 5.5cm or 5% yearly growth
Monitor aortic root frequently in pregnancy, if diameter exceeds 4cm

Medication to slow rate of dilatation.

Question 9

What treatment is given for Long QT syndrome? How does it vary per type?

Answer 9

1/2,5/6

• Beta blockers
• Nicorandil

3

• Mexilitene
• Lidocaine
• IC

Question 10

What are the features of Brugada syndrome?

Answer 10

RBBB
QTc normal
ST elevation V1-3
Episodic VT/VF
SCN5A associated

Question 11

What are the features of ARVC?

Answer 11

Effort induced polymorphic tachycardia LBBB
RV cardiomyopathy (dilated)
T wave inversion V2-3 on resting ECG
Disordered cell junctions

Question 12

What is done in ‘cascade screening’?

Answer 12

Do 3 gen family history
Arrange ECG for 1st degree relatives
Genotype
Second degree relatives in some cases