Genetic Heart Disease Flashcards
What causes a genetic cardiac disease?
Some are inherited, these are multifactorial as theyre based on multiple genes
Some are random
Some are caused by enviromental teratogens.
What teratogens can cause congenital heart disease?
Maternal:
- Anti-epileptics (Foetal Anticonvulsant Syndrome)
- Rubella
- Smoking
- Drinking (Foetal Alcohol Syndrome)
What is the Nuchal Translucency (NT) test?
An ultrasound during pregnancy which measures the buildup of fluid in the back of the babys neck.
A thicker than normal fluid buildup can indicate down syndrome, Edwards syndrome (trisomy 18) and heart problems.
What is down syndrome?
Trisomy in chromosome 21 due to non-disjunction
What are the effects of down syndrome?
ASD/VSD/Tetralogy of Fallot/PDA
- > Intellectual Disability
- > Physical Growth Delays
- > Facial Characteristics
- > Duodenal Atresia (absence/closure of part of the duodenum causing intestinal obstruction in newborns & increased amniotic fluid in pregnancy)
What is Turner’s Syndrome?
No sex chromosome from the father -> 45, X
What are the effects of Turner’s Syndrome?
Coarctation of the Aorta
- > Short Stature
- > Puffy Hands
- > Neck Webbing
- > Gonadal Dysgenesis (loss of germ cells in embryos leads to infertility & a sexually infantile female appearance)
What is Noonan Syndrome?
A mutation in the PTPN11 gene on chromosome 12 (autosomal Dominant inheritance).
This is a gene in the MAPK pathway (mitogen activated protein kinase)
What are the effects of Noonan Syndrome?
Pulmonary Stenosis & Septal Defects
- > Short Stature
- > Neck Webbing
- > Facial Characteristics
- > Cryptorchidism (missing 1 or more testicles)
What conditions are associated with Noonan syndrome due to all affecting different genes in the MAPK pathway? And their symptoms?
Cardiofaciocutaneous (CFC):
Problems with the Ectoderm - Developmental Delay
Leopard Syndrome: Multiple Lentigenes (small proliferation of melanocytes, looks just like freckles, harmless) - Deafness
Costello Syndrome:
Thickened Skin Folds - Susceptible to Warts - Cancer Risk - CARDIOMYOPATHY
What is 22q11 deletion syndrome?
A microdeletion syndrome where a small segment of chromosome 22, q (long) arm, band 1, sub-band 1 is deleted.
It encompasses DiGeorge syndrome and Shpintzen (velocardiofacial) syndrome.
What are the features of 22q11 deletion syndrome?
CATCH22:
Cardiac Malformation (tetralogy of fallot) Abnormal facies Thymic Hypoplasia Cleft Palate Hypoparathyridism 22q11 deletion syndrome
Can also have speech delay/palatal dysfunction, renal issues and psychiatric problems.
What is hypoparathyridism?
under-function of the parathyroid glands -> under-production of the parathyroid hormone
Can lead to low serum calcium levels causing cramping/twitching/tetany
What is William’s Syndrome?
A microdeletion syndrome where 27~ contigous genes on chromosome 7 are deleted. Including those for LIM kinase & elastin.
What are the features of william’s syndrome?
Aortic Stenosis (supravalvular)
- > Hypercalcemia
- > 5th finger clinodactyly (curvature towards 4th finger)
- > Characteristic Face
- > Cocktail Party Manner (very sociable, outgoing and interact easily with stranger)
What are the effects of Foetal Alcohol Syndrome (FAS)
ASD/VSD
What are the effects of Foetal anticonvulsant syndrome, and the specific drugs causing it?
Folate Deficiency which can cause VSD
- > Characteristic Face
- > Malformation Patterns
- > Developmental Delay
Valproate - Phenytoin - Carbamazepine
What are romano-ward and Jervell Lange-Neilsen syndromes?
Long QT syndromes characterised by a prolonged QT segment on an ECG.
What are the features of Romano-Ward & Jervell Lange-Neilsen Syndromes?
Both:
Syncope - Seizure - Sudden Death
Jervell Lange-Neilsen also has congenital Sensorineural Deafness.
What are the triggers for episodes of Romano-Ward and Jervell Lange-Neilsen syndromes?
Emotion - Exercise - Drugs
What is brugada syndrome?
A condition causing a Right Bundle Branch Block (RBBB) which shows up as ST elevation on ECG leads V1-3
What is Marfan’s syndrome?
A multisystem connective tissue disorder involving a deletion in chromosome 15, q arm, band 2, sub band 1. (15q21) which is the fibrillin 1 gene.
How do we diagnose marfan’s syndrome?
The Ghent criteria requires atleast 2 of:
- A family history with it
- 7+ points on the clinical finding list
- A +ve fibrillin 1 gene mutation
What are the features of the Ghent Criteria?
- Fingers reach round wrist due to long digits (arachnodactyly)
- Thumb sign
- Pectus carinatum
- Pectus Excavatum
- Flat Foot
- Hindfoot deformity
- Spontaneous Pneumothorax
- Dural Ectasia (ballooning of dural sac)
- Scoliosis/Kyphosis
- Reduced elbow flexion
- Protrusio Acetabuli (an overly deep femoral socket that may protrude into the pelvis)
- Striae (unexplained stretch marks)
- Myopia (short-sightedness) due to ectopia lentis (lens subluxation i.e. partial dislocation)
- Mitral Valve Prolapse
- Tall/ arm span greater than height
- Facial Features
What are the cardiac features of Marfan’s Syndrome?
- Mitral Valve Prolapse leading to MR
- Aortic Root dilatation (can be aneurysm)
- Aortic Dissection
How is Marfan’s Inherited?
Autosomal Dominant
How is suspected Marfan’s investigated?
Echo - to inspect aortic root and clarify the murmurs
MRI - Of the Lumbar Spine for Dural Ectasia
Pelvic X-Ray - For Protrusio Acetabuli
CXR - Pneumothorax
Genetics Test - Fibrillin 1 mutation.
How is Marfans Managed?
Firstly, with an annual clinical review in which clinical features are assessed for progression and an echo is used to check on the aortic root & valves.
Also B blockers - CCBs - ARBs - ACEIs to control stress on heart
Warfarin if the mitral valve is replaced by a prosthetic (see valvular disease)
Lifestyle changes - Avoid heavy exertion & contact sports
Prophyllactic Aortic Surgery
When would we conduct prophyllactic aortic surgery on a marfans patient?
When the sinus of valsalva > 5.5cm or grows 5% a year.
Or if >4cm in a pregnant woman
Can Marfan Patients have kids?
Yes, theyll have a 50% chance of having it with one affected parent .
Women with Marfans have regular echos through pregnancy to monitor the size of the aortic root as theyre at serious risk of dissection, prophyllactic surgery is possible >4cm.
What are some marfan-related syndromes?
Loeys-Dletz Syndrome
Marfan Syndrome Type 2 (non-ocular)
Familial Thoracic Aortic Aneurysms
MASS Phenotype (marfans without skeletal involvement)
