Genetics of cardiovascular disease Flashcards
Causes of congenital heart disease
Causes of congenital heart disease: Copy number variation (CNV) - whole chromosome (trisomy, monosomy), part of a chromosome.
Single nucleotide variation - mendelian disorders (Noonan/CFC, Marfan). Association - CHARGE: CNV, SNV in CHD7, VACTERL: Unknown SNV in a Fanconi gene, SNV in X-linked Z1C3 gene.
Multifactorial - isolated CHD. Teratogens: rubella, alcohol, anti-epileptic drugs, maternal diabetes mellitus.
Describe characteristics and investigation for Down’s syndrome
Down syndrome: trisomy 21 - 96% maternal non-disjunction, 3% translocation, 2% mosaic. 15% atrio-ventricular septal defects. Duodenal astresia.
In order to see down syndrome do ultrasound and look for nuchal translucency at 12 weeks.
Describe characteristics and pathology of Turner’s syndrome
Turner syndrome (45,X): 30% mosaic, 5% 45,X/46XY. 1/3000LB (20% of SAB). Coarctation of aorta. Short stature, gonadal dysgenesis, puffy hands
Neck weebing: excess nuchal folds, an indicator of prenatal cardiac difficulties - in turner syndrome, noonan, CFC, leopard and costello. In this group of single gene disorders the key cardiac feature is pulmonary stenosis.
Costello syndrome is associated with what risk?
Costello syndrome has a pretty high risk of cardiomyopathy.
Describe characteristics of 22q11 deletion syndrome
22q11 deletion syndrome: cardiac malformation, abnormal facies, thymic hypoplasia, cleft palate, hypoparathyroidism, 22 q11 deletion.
22q11 syndrome encompasses both digeorge and velocardiofacial syndromes.
Di George syndrome characteristics
DiGeorge syndrome: thymic hypoplasia, hypoparathyroidism, outflow cardiac malformation, usually sporadic.
Spritzen syndrome characteristics
Shprintzen syndrome: cleft palate/palatal insufficiency, outflow tract cardiac malformation, characteristic face, autosomal dominant.
Willian’s syndrome characteristics
Willians syndrome: aortic stenosis (supravalvar), hypercalcemia, 5th finger clinodactyly, characteristic face, cocktail party manner. Deletion of elastin on chromosome 7, deletion of contiguous genes, LIM kinase.
What are the causes of congenital cardiac CT disease:
Cardiovascular CT disease: Marfan, Loeys-Dietz, Ehlers Danlos, FTAA.
What are familial cardiomyopathy
Familial cardiomyopathy: HCM and DCM
What are familial arrhythmias
Familial Arrhythmias: Long QT, burgada, CPVT, ARVC
Marfan’s syndrome characteristics and diagnosis
Diagnosis of Marfan 2 positive findings: Cardiovascular system - aortic dilatation/dissection, mitral valve prolapse
Clinical assessment for possible Marfan
Clinical assessment for possible Marfan, examine for the clinical features of Ghent 2010. Arrange echocardiogram to measure diameter at sinus of valsalva, relate to age and BSA. X-ray for protrusio, MRI for dural ectasia if a positive result would make the diagnosis. Undertake genetic testing to confirm clinical suspicion.
Aims in management of Marfan’s
Optimal medical management of marfan - Management aimed at: reducing growth in aortic diameter, controlling blood pressure, surgical intervention when risk of rupture is too high
Optical management of Marfan’s
Optimal management of marfan involves at least annual clinical review: echocardiogram, beta blockers, ARB, prophyllactic aortic surgery if sinus of valsalva exceeds 5.5 cm or 5% growth per year. Monitor aortic root frequently in pregnancy if diameter exceeds 4cm.
Describe the precipitants and mutations causing different types of long QT syndromes
Different kinds of Long QT are controlled by changes in genes in different ion channels.
