Congenital and Genetic Heart Disease Flashcards
What are some of the causes for congenital heart disease?
Copy number variation (CNV) - whole or part of chromosome
Single nucleotide variation (SNV) - mendelian disorders
Associations - Charge or Vacterl
Multifactorial
Teratogens
What are the causes for Down syndrome?
Trisomy 21
Mainly maternal non-disjunction
Less common is translocation or mosaic
What are some life-limiting conditions that can come along with Trisomy 21?
15% have atria-ventricular septal defects
Duodenal atresia
How can down syndrome be detected during pregnancy?
Risk is related to the fluid at back of neck - nuchal translucency
Bigger the area = bigger the risk
Is chromosome abnormality more common in foetuses with CHD than in newborns?
More common that foetuses with CHD have abnormal chromosomes than newborns
Associated with cystic hygroma on scan
What is Turner’ syndrome caused by?
mainly mosiac but can be 45X/ 46XY
What conditions can a person with Turner’s syndrome?
Coarctation of aorta, short stature, gonadal dysgenesis, puffy hands and neck webbing
What congenital conditions is neck webbing seen in?
Turner’s syndrome, Noonan syndrome, CFC syndrome, Leopard syndrome and Costello syndrome
What are the characteristics of Noonan syndrome?
Pulmonary stenosis, short stature, neck webbing, cryptorchidism, characteristic face
Due to mutation in PTPN11 gene on chromosome 12
What are some characteristics of Cardio-Facio-Cutaneous (CFC)?
Noonan- like
Plus ectodermal problems and developmental delay
What are some characteristic features of Leopard syndrome?
Noonan like
Plus multiple lentigines and deafness
What are some characteristics of Costello syndrome?
Noonan like
Plus thickened skin folds, susceptible to warts, cardiomyopathy and later cancer risk
What pathway do these congenital condition genes work in?
MAPK pathway
What are the characteristics of 22q11 deletion syndrome?
Cardiac malformation
Abnormal facies (widened space between eyes, small lips and ears forward0
Thymic hypoplasia
Hypoparathyroidism
22q11 deletion
Also has renal and psychiatric problems
What 2 syndrome does 22q11 deletion syndrome comprise of?
DiGeorge syndrome and Shprintzen Syndrome
How do you diagnose 22q11 deletion syndrome?
Speech delay/ palatal dysfunction is common
Highly variable disorder
If 2 or more features present then test
Only 25% is familial
Explain psychiatric problems and 22q11 deletion syndrome
2/100 schizophrenic patients had condition
4/18 22q11 patients have schizophrenia
Explain 22q deletion as a genomic disease
LCR regions - low copy number repeats and this predisposes to deletion and translocation
What causes William’s syndrome?
Deletion of Elastin on chromosome 7 and deletion of contiguous genes
LIM kinase
What are some characteristics of Williams syndrome?
Aortic stenosis, hypercalcaemia, 5th finger clinodactyly, characteristic face and cocktail party manner
What causes Teratogens?
Foetal alcohol syndrome, antiepileptic drugs, rubella and maternal diabetes mellitus
Describe congenital heart disease and family risk
Recurrence risk is higher in child of mother
Highest sibling risk is in AS, ASD, VSD and PS
What is associated with VSD during pregnancy?
Folate deficiency
Should take folate during pregnancy
What are some genetic cardiac diseases?
Cardiovascular connective tissue disease - Marfan, Loeys-Dietz
Familial arrhythmias
Familial cardiomyopathy
What is Marfan syndrome?
Autosomal dominant
Multisystem
Connective tissue disorder
Mutation in Fibrillin gene on chromosome 15q21 or TGFBR2 gene on chromosome 3p22
Explain Ghent 2010
Diagnosis of Marfan if 2 positive findings in 5 areas of investigation
What are the 5 areas of investigation in Ghent 2010?
Cardiovascular system - aortic dilatation/dissection
Eyes - ectopia lentis
Systemic score > or equal to 7 - skeletal, skin, resp., dural ectasia, mitral valve prolapse, myopia
Fibrillin 1 mutation
What is iridodesis?
Iris shakes as eye moves
Lens wobbles behind eye and makes it shake
Sign of Marfan
What is involved in the clinical assessment for possible Marfan Syndrome?
Ghent 2010
Arrange echo to measure sinus of Valsalva, relate to age and BSA
X- ray and MRI
Undertake genetic testing
Explain TGFB signalling in Marfan syndrome
TGFB signalling affects cell proliferation, differentiation and apoptosis
Deficient in fibrillin have excess TGFB signalling and Marfan features
What is optimal management of Marfan?
At least annual review - echo
BB, ARBs, prophylactic aortic surgery if sinus of Valsalva exceeds
Monitor aortic root frequently in pregnancy
What are the types of aortic root surgery?
Enlarged aorta, Mechanical valve (last longer but needs warfarin) and valve sparing procedure (may need re-op but no warfarin)
What are some Marfan like syndromes?
Loeys-Dietz Syndrome
Familial Thoracic Aortic Aneurysms
BAV/FTAA (bicuspid aortic valve/familial thoracic aortic aneurysm)
MASS syndrome
Explain sudden unexplained death
Between 1 and 40 years
1/3 show no post mortem cause and are assumed to be arrhythmic
Mostly identifiable inherited heart disease in 1st degree relative studies
Mayo Clinic Molecular autopsy series - ion channelopathy
Explain Long QT syndrome
Ramano-Ward syndrome
ECG shows prolonged QTc interval
Repolarisation abnormalities and paroxysmal polymorphic VT (Torsade de Pointes)
Jervell Lange-Nielsen - same as above plus congenital sensorineural deafness
What are the presentations and causes of Long QT syndrome?
Syncope, seizures and sudden death
These can be brought on by emotion, exercise and drugs
What are the types of cardiac ion channels which can cause long QT syndrome?
LQT2 and LQT1
LQT6 and LQT5
LQT3
Result in longer refractory period and can lead to VT
Describe genotype prediction for mutations KCNQ1, KCNH2 and SCN5A
KCNQ1 - exercise (swimming) gives normal/broad T wave pattern
KCNH2 - noise/arousal gives notched T wave pattern
SCN5A - sleep/bradycardia gives biphasic t wave pattern
What are some features of Bragada Syndrome?
SCD or VF/VT and type 1 Brugada ECG
Can cause death and sudden death
Other features include prolonged PR interval, enlarged LV/poor LV function and is more common in young men of Eastern origin
What causes Brugada syndrome?
SCN5A loss of function
What is the management for Brugada syndrome?
Avoid fever, excess alcohol and overeating which increase vagal effects
ICD is also considered
Explain Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Right ventricle does not work properly
This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.
On histology fatty infiltrate of RV
What is some features of ARVC?
ECG - epsilon waves and T wave inversion
SAECG - late potentials
Effort induced VT
FH or pathogenic gene variant
Genes all in cell junction mechanism describe
What genes cause hypertrophic cardiomyopathy sarcomere disease?
Monoallelic (more common) - MYH7
Diallelic genes
Describe HOCM myofibrillar disarray
Electrical signal may get lost and end up in re-entry causing VT
Arrhythmia is caused
Describe dilated cardiomyopathy
Echo features of dilated cardiomyopathy
Family history should be considered
TTN variants account for many DCM types
What is the process of diagnosing an inherited cardiac condition?
Diagnosis in proband - cardiac phenotype and genetic testing
Family history
Assess relatives
Cascade screening of relatives
Prevention of avoidable morbidity and mortality
