Genetics of Cardiovascular Disease Flashcards
What is the chromosomal abnormality of Down syndrome?
Trisomy 21
Cardiac abnormalities associated with down syndrome
AVSD
Other congenital abnormalities with Down syndrome
AVSD
Duodenal atresia
What do down syndrome babies have more of?
Nuchal translucency
What % of foetuses with CHD have abnormal chromosomes?
13%
What is the genetic abnormality of turners syndrome?
45X
What CHD can turner syndrome result in?
Coarctation of aorta
What abnormalities are associated with turner syndrome?
Coarctation of aorta
Short stature
Gonadal dysgenesis
Lymphoedema of hands and feet
What gender gets turners syndrome?
Girls only
What is there a risk of in turners syndrome?
Gonadal cancer
What can neck webbing possibly be an indicator of?
Prenatal cardiac difficulties
What causes neck webbing?
Excess nuchal folds
Syndromes associated with neck webbing
Turners Noonans CFC Leopard Costello
Abnormalities of noonan syndrome
Pulmonary stenosis Short stature Neck webbing Cryptorchidism Characteristic face
What is cryptorchidism?
One or both of the testes fail to descend from the abdomen into the scrotum
What is the genetics of noonan syndrome?
PTPN11 gene (chromosome 12) Autosomal dominant
What gender gets noonan syndrome?
Both boys and girls
What does CFC stand for?
Cardio-facio-cutaneous
What abnormalities are found in CFC?
Noonan like
Ectodermal problems
Developmental delay
What gender gets CFC?
Boys and girls
What abnormalities are found leopard syndrome?
Noonan like
Multiple lentigines (small pigmented spots on skin)
Deafness
Presentation of Costello syndrome
Noonan syndrome Thickened skin folds Susceptibility to warts CARDIOMYOPATHY Late cancer risk
What is the pneumonic to remember the presentation of 22q11 deletion syndrome?
CATCH 22
- cardiac malformation
- abnormal facies
- thymic dysplasia
- cleft palate
- 22q11 deletion (renal, psychiatric (schizophrenia), floppy overfolded ears, small mouth, bulging tip of nose, speech delay, very variable)
What syndromes does 22q11 deletion syndrome emcompass?
Both DiGeorge syndrome and Velocardiofacial (Shpritzen) syndrome
Features of DiGeorge syndrome
Thymic hypoplasia
Hypoparathyroidism
Outflow tract cardiac malformation
Sporadic
Features of shprintzen syndrome
Cleft palate/palatal insufficiency
Outflow tract cardiac malformation
Characteristic face
AD
Cardiac manifestations of Williams syndrome
Aortic stenosis (supravalvular)
Abnormalities of Williams syndrome
Aortic stenosis Hypercalcaemia 5th finger clinodactyly Characteristic face Cocktail party manner
Genetics of Williams syndrome
Deletion of elastin on chromosome 7
Deletion of contiguous genes
LIM kinase
Inheritance of marfans syndrome
AD
Genetics of marfans syndrome
Fibrillin 1 gene
Chromosome 15q21
Presentation of marfans syndrome
Tall stature Long fingers AORITC DISSECTION Ectopia lentis Scoliosis
What is ectopia lentis?
Lens of the eye slips out of place and can cause visual problems
Another name for long QT syndrome
Romano-Ward syndrome
Features of long QT syndrome
Syncope Seizure Sudden death ECG - prolonged QTc interval Repolarisation anomalies (T/U waves) Paroxysmal polymorphic VT
Features of brugada syndrome
RBBB QTc normal ST elevation V1-V3 Episodic VT/VF Rest and sleep M > F
Presentation of hypertrophic cardiomyopathy
Sudden death
Who is sudden death of hypertrophic cardiomyopathy common in?
< 14 y/o
Symptomatic
Features of dilated cardiomyopathy
History or presyncope or syncope
Tachy or brady arrhythmia
ECG investigation
What genetic tests should be carried out with dilated cardiomyopathy?
LMNA
SCN5A
Dystrophin
Sacromere genes
Causes of congenital heart disease
Chromosomal Microdeletions Single gene Teratogens Viral Isolated (multifactorial)
Features of teratogens
IUGR < 10th centile Head < 10th centile SN hearing loss Long filtrium Increased space between eyes Visuomotor difficulties Fine motor difficulties ADHD
Examples of teratogens
Alcohol
Antiepileptic drugs
Rubella
Maternal DM
What is VSD associated with in the mother?
Folate deficiency
Clinical diagnosis of marfans syndrome
2 system findings must be +ve CVS - aortic dilatation/dissection Eyes - ectopia lentis Systemic score >7 - skeletal - skin - resp - dural ectasia - MVP - myopia FH Fibrillin 1 mutation
What are the systemic scores for skeletal features of marfans?
ULSR and SHR Scoliosis/kyphosis Pectus deformity Thumb and wrists Foot / ankle Reduced elbow extension < 170
What are some other systemic score features for marfans?
Myopia > 3 dioptres MVP Pneumothorax Dura Striae Face Protrusio Acetabuli
What additional tests should be done in marfans?
ECHO mandatory !
MRI/Pelvic X ray if need
What % of marfans patients have the fibrillin 1 mutation?
70-90%
What is cascade screening?
3 generation FH
ECGs for 1st degree relatives
2nd degree special cases
Management of marfans disease
Annual clinical review ECHO Beta blockers ARBs Prophylactic aortic surgery if sinus Valsalva exceeds 5.5cm
What heart sounds are classically associated with a VSD?
Pansystolic murmur Lower left sternal border Heaving apex beat Split S2 Sings of pulmonary HTN RHF
