Genetics and Cardiovascular Disease Flashcards
Causes of congenital heart disease
Copy number variation
Single nucleotide variation
Multifactorial
Teratogens
Down syndrome genetic variation
Trisomy 21 non-disjunction
Down syndrome results in
Atrio-ventricular septal defects
Duodenal aterisa
Down syndrome pregnancy risk identified by
Maternal age
Nuchal translucency at 12 weeks
Cystic hygroma can result in
Coronary heart disease
Neck webbing
Excess nuchal folds
Neck webbing is found in
Turner syndrome Noonan syndrome CFC syndrome Leopard syndrome Costello syndrome
Neck webbing can be and indicator of
Prenatal cardiac difficulties
Turner syndrome genetic variation
Missing X chromosome in females
Turner syndrome presentation
Coarctation of the aorta
Short stature
Gonadal dysgenesis
Puffy hands
Noonan syndrome genetic variation
PTPN11 gene mutation (chromosome 12, autosomal dominant)
Noonan syndrome presentation
Pulmonary stenosis Short stature Neck webbing Characteristic face Cryptorchidism
Cardio-facio-cutaneous (CFC) syndrome rpresentation
Noonan-like features
Ectodermal problems
Developmental delay
Leopard syndrome presentation
Noonan-like features
Multiple lentigenes
Deafness
Costello syndrome presentation
Noonan-like features Thickened skin folds Susceptible to warts Cardiomyopathy Later cancer risk
22q11 deletion syndrome presentation
Cardiac malformation Abnormal facies Thymic hypoplasia Cleft palate Hypoparathyroidism
22q11 deletion syndrome can result in
Renal and psychotic complications
Williams syndrome genetic variation
Deletion of elastin on chromosome 7
Deletion of contiguous genes
LIM kinase
Williams syndrome presentation
Aortic stenosis Hypercalcemia 5th finger clinodactyly Characteristic face Cocktail party manner
Teratogens
Alcohol
Anti-epileptic drugs
Rubella
Maternal diabetes mellitus
Multifactorial inheritance
Interaction of many abnormal factors that cause bypass of threshold
Ventricular septal defeat is associated with what
Folate deficiency
Genetic cardiac diseases
Cardiovascular connective tissue disease
Familial arrhythmias
Familial cardiomyopathy
Marfan’s syndrome genetic variation
Fibrillin 1 gene, chromosome 15q21 (autosomal dominant)
Marfan’s syndrome presentation
Tall stature Pectus carinatum Arachnodactyly Aortic dilation Mitral valve prolapse Ectopic lentis Disproportionally long arms and legs
Deficient fibrillin results in excess production of
TGFbeta
Management of Marfan
At east annual clinical review Echocardiogram Beta blockers ARB Prophylactic aortic surgery if sinus or velaslva exceeds Monitor aortic root in pregnancy
Aortic root surgery options
Remove and replace who root including mechanical valve
Or put in sleeve to protect aortic root, sparing the valve
Romano-Ward syndrome
Type of long QT syndrome resulting in a prolonged QT interval in ECG
Symptoms of Romano-Ward syndrome
Syncope
Seizures
Sudden death
Triggers of arrhythmia in Romano-Ward syndrome
Emotions
Drugs
Exercise
Features of Romano-Ward syndrome
Prolonged QT interval
Depolarisation anomalies
Paroxysmal polymorphic ventricular tachycardia
Brugada syndrome
Electrical activity with heart is abnormal
Features of Brugada syndrome
Ventricular fibrillation or tachycardia
Prolonged PR interval
Enlarged, poor functioning LV
Brugada syndrome genetic variation
SCN5A loss of function
Management of Brugada syndrome
Avoid fever, alcohol and over-eating
Implantable cardioverter-defibrillator (ICD)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Cardiomyopathy affecting the ventricles and causes arrhythmias
Features of arrhythmogenic right ventricular cardiomyopathy (ARVC)
ECG - epsilon waves, T wave inversion SAECG - late potentials Ventricular tachycardia Echo/MRI - RV abnormality of movement Histology - fatty infiltration of RV
Hypertrophic cardiomyopathy
Portion of heart becomes thickened without an obvious cause
Hypertrophic cardiomyopathy is caused by dysfunction of
Sarcomere from abnormality of sarcomere genes
Symptoms of hypertrophic cardiomyopathy
Syncope Dyspnoea Fatigue Exertional presyncope Palpitations Anginas like chest pain Asymptomatic
Modifiers of hypertrophic cardiomyopathy
Lifestyle
Other genes
Genetic testing for dilated cardiomyopathy
Titin
SCN5A
Sarcomere genes
Dystrophin
Largest gene in the genome
Titin
Next generation sequencing
Method for sequencing entire genome all at once
