What are some causes of congenital heart disease?
Copy number variation (CNV)
Single nucleotide variation (SNV)
What does CNV stand for?
Copy number variation
What does SNV stand for?
Single nucleotide variation
What are examples of copy number variations?
Whole chromosome (trisomy, monosomy)
Part of a chromosome (22q11 deletion, Williams)
What is an example of single nucleotide variation?
Mendelian disorder (Noonan/CFC, Marfan)
What are examples of teratogens?
What causes down syndrome?
Trisomy 21 (usually due to maternal non-dysjunction)
What percentage of people with down syndrome have atrioventricular septal defects?
How does the risk that a pregnancy has down syndrome increase?
With maternal age
What does CHD stand for?
Coronary heart disease
What causes Turner's syndrome?
45, X (only affects females)
What are some characteristics of Turner's syndrome?
Coarctation of aorta
What is neck webbing?
Excess nuchal folds
An indicator of prenatal cardiac difficulties
What is neck webbing an indicator of?
Prenatal cardiac difficulties
What genetic diseases is neck webbing present in?
What are characteristics of Noonan syndrome?
PTPN 11 gene (chromosome 12)
What does MAPK pathway stand for?
Mitogen activated protein kinase pathway
What is the MAPK pathway?
Chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus
What are characteristics of 22q11 deletion syndrome?
Encompasses both DiGeorge and Velocardiofacial syndrome
What is 22q11 deletion syndrome a combination of?
DiGeorge and Velocardiofacial syndrome
What are characteristics of DiGeorge syndrome?
Outflow tract cardiac malformation
What are characteristics of Velocardiofacial syndrome?
Outflow tract cardiac malformation
What kind of inheritance does Velocardiofacial syndrome show?
What are characteristics of Williams syndrome?
5th finger clinodactyly
Cocktail party manner
Delection of elastin on chromosome 7
Deletion of contiguous genes
What causes Williams syndrome?
Deletion of elastin on chromosome 7 and contiguous genes
What is foetal alcohol syndrome?
Diagnostic term to describe the impacts on the braina dn body of people prenatally exposed to alcohol during pregnancy
What is a diagnostic term used to describe the impacts on the braina dn body of people prenatally exposed to alcohol during pregnancy?
Foetal alcohol syndrome
What model does multifactorial inheritance use?
What are some examples of simple congenital heart diseases?
Patent ductus arteriosus
Atrial septal defect
Ventricular septal defect
Tetralogy of Fallot
What is ventricular septal defect associated with?
What is folate deficiency associated with?
Ventricular septal defect
What is folate?
What are different categories of cardiac genetic disease?
Cardiovascular connective tissue disease
What are examples of cardiovascular connective tissues diseases that are genetic?
What are examples of familial arrhythmias?
What are examples of familial cardiomyopathy?
Hypertrophic cardiomyopathy (HCM)
Dilated cardiomyopathy (DCM)
What does HCM stand for?
What does DCM stand for?
What kind of inheritance does Marfan syndrome show?
What causes Marfan syndrome?
Fibrillin 1 gene which is located chromosome 15q21
What does diagnosis of Marfan require?
2 positive findings of the following:
Aortic dilation/dissection (cardiovascular)
Ectopia lentis (eyes)
Systemic score more than or equal to 7 (includes skeletal, skin, respiratory, dural ectasia, mitral valve prolapse and myopia)
Fibrillin 1 mutation
What do people with Marfan syndrome generally look like?
Tall and thin
When should you do a genetic test for Marfan syndrome?
In a suspected case when a positive result would change the diagnosis (such as case with only a single major feature)
Explain the biochemistry of Marfan syndrome?
1) TGF beta and fibrillin are both secreted into the extracellular matrix and interact in vitro
2) Incorporation of fibrillin into microfibrils results in the proteolytic release of TGF beta
3) TGF beta signalling affects cell proliferation, differentiation and apoptosis
What does TGF beta stand for?
Transforming growth factor beta
What is proteolytic?
Breakdown of proteins into smaller polypeptides or amino acids
What does the management of Marfan syndrome involve?
Annual clinical reviews which includes:
Angiotensin II receptor blockers
Prophylactic aortic surgery if sinus or Valsalva exceeds 5.5cm or 5% frowth per year
Monitor aortic root frequently in pregnancy if diameter exceeds 4cm
What are examples of Marfan like syndromes?
Familial thoracic aortic aneurysm
What are characteristics of Loeys-diets syndrome?
Skin and skeletal findings
What are characteristics of MASS phenotype?
Mitral valve prolapse
Mild aortic dilation
Minor skeletal involvement
What is sudden unexpected death syndrome?
Sudden arrhythmic death of adults or children, usually during sleep
What age group usually die from sudden unexpected death syndrome?
Beteen 1 year and 40 years
What are the typical causes of sudden unexpected death syndrome?
Inherited heart disease
Ion channelopathy (most are long QT syndrome)
What is long QT syndrome?
Condition that affects repolarisation of the heart after a beat
What are symptoms of long QT syndrome?
What are exacerbating factors for long QT syndrome?
What does the ECG for long QT syndrome show?
Prolonged QT interval
Repolarisation anomalies (T/U waves)
What are some mutations that suggest precipitants of arrhythmia?
What is the precipitant of arrhythmia for KCNQ1 mutation?
What is the precipitant of arrhythmia for KCNH2 mutation?
What is the precipitant of arrhythmia for SCN5A mutation?
What is Brugada syndrome?
Condition that disrupts normal rhythm of the heart
What are the different types of Brugada syndrome?
What is seen in Brugada syndrome?
Prolonged PR interval
Enlarge left ventricle
Who usually suffers from Brugada syndrome?
Young men, especially of far Eastern origin
What mutation if Brugada syndrome due to?
SCN5A and 11 other genes
What is the management of Brugada syndrome?
Avoid fever, excess alcohol and overeatin
Implantable cardioverter defibrillator (ICD)
What does AVC stand for?
Atrioventricular canal defect
What is atrioventricular canal defect?
Hole between the chambers of the heart
What is atrioventricular canal defect diagnosed by?
Echocardiogram or MRI
What does the ECG for atrioventricular canal defect show?
T wave inversion
What does histology for atrioventricular canal defect show?
Fatty infiltration of right ventricle
What is hypertrophic cardiomyopathy?
Heart muscles (myocardium) becomes abnormally thick
What is it called when the heart muscles (myocardium) becomes abnormally thick?
What is the prevalence of hypertrophic cardiomyopathy?
What is the presentation of hypertrophic cardiomyopathy?
What is the mortality of hypertrophic cardiomyopathy?
6% per year diagnosed in childhood
2.5% per year diagnosed in adult life
0.5% per year diagnosed in screening
What is dilated cardiomyopathy?
Heart becomes enlarged and cannot pump blood effectively
What is it called when the heart becomes enlarged and cannot pump blood effectively?
What should be done before diagnosing dilated cardiomyopathy?
Ischaemic heart disease (angiography)
Skeletal muscle disease (neurology/genetic evaluation)
Alcohol abuse (history and biochemical evidence)
Exposure to cardiotoxic (history)
What may genetic testing for dilated cardiomyopathy include?
What is the largest gene in the genome?
Titan with 363 exons and 38138 amino acids
What are different kinds of genetic sequencing?
Next generation sequencing (can read many genes at once)
What is the difference between Sanger and next generation sequencing?
Next generation sequencing can read many genes at once
What is genomics?
Branch of molecular biology concerned with the structure, function evolution and mapping of genomes
What is the branch of molecular biology converned with the structure, function, evolution and mapping of genomes?
What is genetic cardiology conditions diagnosed by?
Cardiac phenotype and genetic history