Congenital heart disease genetics

Question 1

Causes

Answer 1

Chromosomal abnormalities: Trisomies/Monosomies
Single gene mutations
Microdeletions
Teratogens : alcohol, rubella, diabetes, anti-epileptic drugs
Others: VACTERAL- developmental pathways

Question 2

Chromosomal abnormalities diseases related to CVS

Answer 2

Down’s syndrome: chromosome 21 trisomy- Atrial septal defects
Turner’s syndrome : 45, X trisomy- Co-archtation of the aorta

Question 3

Examples of diseases caused by a micro deletion

Answer 3

22Q11 deletion

William’s syndrome

Question 4

22q11 deletion

Answer 4

symptoms:
Congenital heart disease
Abnormal facial dysformity 
Thymic hyperplasia 
Cleft palate 
Hypoparathydoism
types:
-DIGEORGE: milder version
-SHPRINTZEN

Question 5

William’s syndrome

Answer 5

• aortic stenosis
• hypercalcemia
• 5th finger clinodactaly
• deletion of elastin of chromosome 5
• deletion of contiguous genes- many repetitions removed

Question 6

Marfans

Answer 6

• autosomal dominant connective tissue disorder
• due to Fibirillin mutation
• single gene mutation

Question 7

Marfan’s symptoms

Answer 7

• tall stature
• dural ectasia- enlargement of dura surrounding the dural sac
• Mitral valve prolapse
• Aortic root dilation/dissection
• respiratory: pneumothorax
• skeletal: kyphosis, scoliosis
• myopia

Need a systemic score >7 to be Marfan’s

Question 8

Testing for Marfan’s

Answer 8

• increase in TGFB
• in vitro TGFB and fibrillar react together
• with fibrillar mutation- more TGFB
• TGFB leads to cell proliferation

Question 9

Long QT syndrome

Answer 9

• autosomal dominant
• due to abnormal repolarisation/depolarisation of myocytes due to abnormalities in calcium ion channels
• only some cells affected- can lead to establishment of a re-entrant circuit- Torsades de Points

Question 10

Triggers, mutation and T wave presentation in Long QT

Answer 10

Trigger: exercise Mutation: KCNQ1 T wave: normal
Trigger: Noise Mutation: KCNH2 wave: notched
Trigger: rest/bradycardia Mutation: SCN51 wave: biphasic

Question 11

Romano-ward syndrome

Answer 11

• type of Long QT
• symptoms: dizziness, syncope, cardiac failure
• Triggers: drugs, exercise

Question 12

Treatment of Long QT

Answer 12

QT1: -Beta blockers -Nicorandil
QT3: -lidocaine -IVC

Question 13

Management of marfans

Answer 13

• beta blockers
• ECHO
• ACEI
• monitor aortic root if more than 4cm during pregnancy
• prophilactic surgery if valve >5.5cm

Question 14

Brugada syndrome

Answer 14

• normal QT
• ST elevation
• Associated with SCN5A mutation
• episodic VT/VF

Question 15

What pathway are these mutations associated with

Answer 15

MAPK- mitogen activated protein kinase pathway

Question 16

What is cascade screening?

Answer 16

• 1 abnormal ECG
• 3 generation family history
• arrange ECG for primary relatives

Question 17

chromosome defect diseases

Answer 17

Turners- 45X- aortic dissection, co-archtation

Downs- Atrial septal defects