Genetics and Cardiovascular Disease Flashcards by Lucy Jefford

What is congenital heart disease?

Disorders causing cardiac malfunction present at birth

How well did you know this?

Not at all

Perfectly

What happens in copy number variation disorders?

There is an extra chromosome- like Down’s syndrome
There is a chromosome missing- Turner’s syndrome

How well did you know this?

Not at all

Perfectly

What happens in single nucleotide variation?

Change in one single base

How well did you know this?

Not at all

Perfectly

What are some of the features of CHARGE association?

Coloboma
Heart defects
Atresia of the choanae
Retardation of growth
Genital abnormalities
Ear abnormalities

->each begins w CHARGE

How well did you know this?

Not at all

Perfectly

What are some of the features of VACTRL association?

Vactyrl anomalies
Anorectal atresia
Cardiac defects
Tracheoesophageal fistula
Renal anomalies
Limb abnormalities.

->each begins with VACTRL

How well did you know this?

Not at all

Perfectly

How can CHARGE association occur?

Copy Number Variation sometimes
Single nucleotide variation in CHD7

How well did you know this?

Not at all

Perfectly

How can the VACTRL association change occur?

Change in Fanconi gene

How well did you know this?

Not at all

Perfectly

Which foetal environmental factors can result in the development of congenital HD?

Rubella, alcohol, anti-epileptic drugs, maternal diabetes mellitus

How well did you know this?

Not at all

Perfectly

Why does down’s Syndrome occur?

Trisomy 21- extra chromosome

How well did you know this?

Not at all

Perfectly

Which congenital heart issues may those with Down’s Syndrome experience?

Atrio-ventricular septal defects

How well did you know this?

Not at all

Perfectly

Which congenital heart issues may those with Turner’s Syndrome experience?

Coarctation of aorta (narrowing)

How well did you know this?

Not at all

Perfectly

What can measuring nuchal folds (skin behind the neck) help with?

Helps with diagnosing genetic conditions like Down’s Syndrome.

How well did you know this?

Not at all

Perfectly

What are some of the symptoms of 22q11 deletion syndrome?

C ardiac malformation
A bnormal facies
T hymic hypoplasia
C left palate
H ypoparathyroidism
22 q11 deletion

How well did you know this?

Not at all

Perfectly

What % of 22q11 deletion syndrome are familial?

25%

How well did you know this?

Not at all

Perfectly

William’s syndrome can increase risks of which cardiac issue?

Aortic stenosis

How well did you know this?

Not at all

Perfectly

What causes the cardiac problems in those with William’s Syndrome?

Deletion of Elastin on chromosome 7

How well did you know this?

Not at all

Perfectly

What is the cause of the physiological/learning factors of William’s Syndrome?

Deletion of adjacent or contiguous genes, including LIM kinase

How well did you know this?

Not at all

Perfectly

What is teratogens?

Foetal alcohol syndrome

How well did you know this?

Not at all

Perfectly

List four of the cardiovascular connective tissue disorders.

-Marfan
-Loeys-Dietz
-Ehlers Danlos
-FTAA

How well did you know this?

Not at all

Perfectly

List four Familial Arrhythmias.

Long QT
Brugada
CPVT
ARVC

How well did you know this?

Not at all

Perfectly

List two Familial Cardiomyopathy.

HCM
DCM

How well did you know this?

Not at all

Perfectly

What happens in vascular ehlers donlos?

Arteries, valves and tendons are much more likely to rupture.

How well did you know this?

Not at all

Perfectly

What type of genetic disorder is Marfan’s Syndrome?

Autosomal dominant

How well did you know this?

Not at all

Perfectly

Which gene becomes mutated in those with Marfan’s Syndrome?

Fibrillin 1 gene

How well did you know this?

Not at all

Perfectly

Which chromosome is fibrillin 1 gene?

Chromosome 15

What are some of the features of Marfan's syndrome?

-Tall stature -Long fingers -Lens subluxation -Mild aortic root dilatation

What may happen to the CVS which is indicative of Marfan's syndrome?

Aortic dilatation/dissection

What may happen to the eyes which is indicative of Marfan's syndrome?

Ectopia lentis

Which six things are looked at to help get a systematic score in those with suspected Marfan's Disease?

l Skeletal l Skin l Respiratory l Dural ectasia l Mitral valve prolapse l Myopia

What is the name of the diagnosis classification for Marfan's Syndrome?

Ghent 2010

Which investigation should be carried out if you suspect Marfan's Syndrome and what should you be doing?

ECHOto measure diameter of sinus of Valsalva

What other tests can be carried out to confirm a diagnosis of Marfan's Syndrome?

Xray MRI Genetic testing

What can cause excess signalling which can lead to cell proliferation and Marfan's?

Excess TGF beta causes excess TGF beta signalling

What is the TGF beta antagonist?

Losartan

What is the aim of management of Marfan's Syndrome?

Reducing growth in aortic diameter Controlling BP

What is the intervention when the risk of aortic rupture if too high?

Surgical intervention

As the aim of management is to prevent the aorta becoming any wider, how is this recorded?

Annual ECHO

How much growth does there need to be in the Sinus of Valsalva for surgery to be undertaken?

5.5.cm or 5% per year 2mm in adults

Which drug might help reduce the growth of the Marfan aorta?

Beta blockers Angiotensin II receptor blockers

What are the options for aortic surgery?

Replace the aorta with a Dacron graft Replace the aortic valve w a mechanical valve Replace aortic root

What is one of the disadvantages of a mechanical valve?

Patient needs to take anticoagulants for life

What is the disadvantage of a aortic root replacement?

Although no anticoagulant is required, patient may need further surgery in the future.

What are some of the features of QT syndorme?

Prolonged ECG QT interval Ventricular tachycardia Syncope

What is the name of the autosomal dominant form of QT syndrome?

Romano-ward syndrome

What is the name of the autosomal recessive form of QT syndrome?

Jervell Lange-Neilsen

What can changes in the potassium channel lead to?

Delayed repolarisation of cardiac muscle cells

Changes to which gene can cause Long QT 1?

KCNQ1

Changes to which gene can cause Long QT 2?

KCNQ2

In those with Long QT 1, what can precipitate arrhythmia?

Diving/swimming into cold water

In those with Long QT 2, what can precipitate arrhythmia?

Loud sudden noise

Long QT 1 responds well to which treatment?

Beta blockers

What are some of the features of Brugada syndrome?

Ventricular arrhythmia- causing syncope or sudden death Abnormal PR interval Abnormal LV function

How can you diagnose Brugada syndrome?

By carrying out a Ajmaline challenge test.

What is Ajmaline?

Sodium channel blocker

What are some of the management options for Brugada syndrome?

Avoiding fever, excess alcohol and overeating.

What can be given to those who have had an arrhythmia and also have Brugada syndrome?

ICD- implantable cardiac defibrillator

What is ARVC?

RV does not function correctly and gets infiltration by fat and fibrosis.

What is the most commonly inherited cardiac disease?

Hypertrophic Cardiomyopathy

What happens in Hypertrophic Cardiomyopathy?

Heart muscle is thickened and enlarged

What is the most common genetic cause of Hypertrophic Cardiomyopathy?

Mutation of MYBPC3

What can hypertrophic cardiomyopathy cause?

Obstruction to blood flow Arrhythmia

What is the largest gene in the genome?

Titin

What can occur due to truncating variants in titan?

Dilated cardiomyopathy

Which sequencing allows us to look at titan?

Next generation sequencing

What is the main advantage of next generation sequencing?

Allows us to do sequencing on a much bigger scale.

What are the five categories that gene variants can be classified by?

Pathogenic Likely pathogenic Uncertain Likely benign Benign