Genetics and Cardiovascular Disease Flashcards
Causes of Congenital Heart Disease (4)
Copy Number Variation
Single Nucleotide Variation
Multifactorial
Teratogens
Copy Number Variations Examples
Whole chromosome (trisomy, monosomy)
Part of a chromosome (22q11 deletion Williams)
Examples of Single Nucleotide Variation
Mendelian disorders (Noonan/CFC, Marfan, SVAS, Holt-oram)
Multifactorial Examples (2)
Isolated CHD
VACTERL association
Examples of Teratogens (4)
Rubella
Alcohol
Antiepileptic drugs
Maternal DM
Down syndrom causes ___% of AV septal defects
15
What is duodenal Atresia
- congenital absence or complete closure of a portion
Indications of CHD in CNV
Nuchal translucency
Cystic Hygroma is
• Fluid filled sac that results from a blockage in the lymphatic system
Features of Turner Syndrome (4)
- Coartation of aorta
- Short stature
- Gonadal dysgenesis
- Puffy hands
What diseases are neck webbing found (Nuchal folds) (5)
Turner Noonan CFC Leopard Costello
features of Noonan Syndrome (5)
Pulmonary Stenosis Short stature Neck webbing Cryptorchidism Characteristic face
What mutation causes Noonan Syndrome
PTPN11 gene (Chr 12)
Features of CFC (3)
Noonan like
Ectodermal problems
Developmental delay
Leopard Syndrome features (3)
Noonan-like
Multiple lentigines
Deafness
features of Costello Syndrome (5)
Noonan-like Thickened skinfolds Susceptible to warts Cardiomyopathy Later cancer risk
Features of 22q11 Deletion Syndrome
- C ardiac malformation
- A bnormal Facies
- T hymic hypoplasia
- C left palate
- H ypoparathyrodism
- 22 q11 deletion
What 2 syndrimes does 22q11 deletion syndrome encompass
Digeorge
Shprintzen
Features of Williams Syndrome (5)
- Aortic stenosis
- Hypercalcaemia
- 5th finger clinodactyly
- Characteristic face
- Cocktail party manner
What mutation causes Williams Syndrome (2)
- Deletion of elastin on chromosome 7
* Deletion of contiguous genes
What is VSD associated with
Folate deficiency
Genetic Cardiac Disease
Cardiovascular connective tissue
Familial Arrhythmias
Familial Cardiomyopathy
An example of a cardiovascular connective tissue disease
Marfan
Example of Familial Arrhythmias (2)
Long QT
Brugda
Familial Cardiomyopathy
HCM
DCM
Features of Marfan (9)
- Tall stature
- Pectus carinatum
- Myopia
- Scoliosis
- Arachnodactyly
- Aortic root dilatation
- Lens subluxation
- FH- parent dies of aortic aneurysm
- Systemic score>7
When should you do a genetic test in a suspected index case
When the positive result would change the diagnosis
A deficiency of what leads to Marfans Syndrome
TGFB
What does TGFB do
When fibrillin is incorporated into microfibrils it results in the proteolytic release of TGFB and it is responsible for cell signalling, differentiation and apoptosis
Management of Marfans Syndrome
• ECHO
• B blockers
• Angiotensin II receptor blockers
• Prophylactic aortic surgery if sinus or Valsalva exceeds 4cm
Monitor aortic root diameter in pregnancy
Mechanical valve as a prophylactic surgery (2)
Last longer
Warfarin
Valve sparing surgery (2)
No warfarin
May need re-operation
Marfan-like syndromes (3)
- Loeys-Dietz Syndrome
- Familial Thoracic Aortic Aneurysms
- MASS phenotype
Long QT syndrome example
Romano-ward syndrome
Features of Romano-ward syndrome
Syncope
Seizure
Sudden death
What does the ECG show in Long QT syndrome
Prolonged QTc interval
Repolarisation anomalies
T wave pattern for mutation KCNQ1
Normal/broad
T wave pattern for mutation KCNH2
Notched
T wave for mutation SCN5A
Biphasic
Brugada
- Prolonged PR interval
- Enlarged LV/ poor LV function
- More common in young men especially of far eastern origin
- SCN5A loss of function
AVC
Impairment of RV
Histology of AVRC
Fatty infiltration of RV
ECG of AVC
Epsilon waves
T wave inversion
Hypertrophic Cardiomyopathy Sarcomere Disease MYH7
Beta cardiac myson
Hypertrophic Cardiomyopathy Sarcomere Disease MYBPC3
Myosin binding protein
Hypertrophic Cardiomyopathy Sarcomere Disease TNNT2
Cardiac troponin T
Hypertrophic Cardiomyopathy Sarcomere Disease TNNI3
Cardiac troponin
