Genetic and Cardiovascular Disease Flashcards
Name some causes of congenital heart disease
Chromosomal Microdeletions Single gene Teratogens Other Multifactorial
What abnormalities of chromosomes can cause a congenital heart disease?
Trisomies/monosomies
What congenital heart diseases can be caused by microdeletions?
22q11 (DiGeorge)
Williams
What congenital heart disease can be caused by single gene abnormalities?
Noonan
Marfan
Name 3 teratogens
Rubella
Alcohol
Anti-epileptic drugs
What is the chromosomal abnormality in Down Syndrome?
Trisomy 21 - extra chromosome due to maternal non-disjunction
What defects are associated with Down syndrome?
Atrio-ventricular septal defect (15%)
Duodenal atresia
How can Down Syndrome be detected in the embryo?
Ultrasound scan:
Measure the nuchal translucency at 12 weeks (space between back of neck) - larger in Down’s babies
How does the risk of Down syndrome change with increasing maternal age?
Increases risk
What is associated with CHD in foetus’?
Cystic hydroma (abnormal growths that usually appear on a baby’s neck or head) - associated with chromosomal abnormalities
Why do more foetus’ with CHD have abnormal chromosomes than newborns with CHD?
Due to natural loss of pregnancies with CHD- ~50% don’t survive to term
What is the chromosomal abnormality in Turner Syndrome?
Incomplete X chromosome (45, X) - therefore they develop as females
What defects are associated with Turner syndrome?
Coarctation of aorta
Short stature
Gonadal dysgenesis (loss of germ cells on the developing gonads)
Neck webbing
Puffy hands in newborns
What is mosaic Turner syndrome?
45, XY - mixed gonadal dysgenesis (the presence of some male structures as well as a uterus, vagina, and fallopian tubes)
Why does neck webbing arise in CHD?
Due to excess nuchal folds
What syndromes does neck webbing occur in?
Turner Noonan CFC Leopard Costello
What defects are associated with Noonan syndrome?
Pulmonary stenosis Short stature Neck webbing Cryptorchidism Characteristic face
What type of chromosomal mutation causes Turner syndome?
Monosomy
What type of chromosomal mutation causes Down syndrome?
Trisomy
What is the gene affected in Noonan syndrome?
PTPN11 gene
What are the features of cardio-facio-cutaneous (CFC) syndrome?
Noonan-like appearance
Ectodermal problems
Developmental delay
What are the features of Leopard syndrome?
Noonan-like appearance
Multiple lentigines
Deafness
What are the features of Costello syndrome?
Noonan-like appearance Thickened skin folds Susceptibility to warts Cardiomyopathy Cancer risk in later life
What are the CATCH 22 features of 22q11 deletion syndrome)
C - cardiac malformation A - abnormal facies T - thymic hypoplasia C - cleft palate H - hypoparathyroidism 22 - 22q11 deletion
What are the other features of 22q11 deletion syndrome?
Renal and psychiatric problems
Speech delay
Palatal dysfunction
Very variable disorder
What syndromes are encompassed by 22q11 syndrome?
DiGeorge and Shprintzen (velocardiofacial)
What are the features of DiGeorge syndrome?
Thymic hypoplasia
Hypoparathyroidism
Outflow tract cardiac malformation
Usually sporadic
More severe and acute manifestation
What are the features of Sphrintzen syndrome?
Cleft palate
Outflow tract cardiac malformation
When should genetic testing be done for 22q11 deletion syndrome?
If 2 or more clinical features are present
What is the relationship between psychiatric disorders and 22q11 syndrome?
22q11 deletion associated with schizophrenia, depression and bipolar affective
What type of chromosomal defect causes 22q11?
Chromosomal copy variation where there is a loss of part of chromosome 22
What are the features of Williams syndrome?
Aortic stenosis Hypercalcaemia 5th finger clinodactyly (curving) Characteristic face "cocktail party manner" - children will have no speech delays but conversations may not make sense/patient might not understand what you're saying
What genetic abnormalities are seen in Williams syndrome?
Deletion of elastin on chromosome 7
Deletion of contiguous genes
Deletion of LIM kinase
What are the common teratogens?
Alcohol - foetal alcohol syndrome
Anti-epileptic drugs
Rubella
Maternal diabetes mellitus if poorly controlled
What are the features of foetal anticonvulsant syndrome?
Characteristic face
Malformation patterns
Developmental delays
Common and specific features
Describe the multifactorial inheritance: threshold model
Variety of factors can contribute to risk of developing disease, but that risk increased if the is FH of the condition - increases threshold
What defect is VSD associated with?
Folate deficiency
What are 4 cardiovascular connective tissue diseases caused by genetic abnormalities?
Marfan
Loeys-Dietz
Ehlers Danlos
FTAA
What are 4 familial arrhythmias caused by genetic abnormalities?
Long QT syndrome
Brugada
CPVT
ARVC
What are 2 familial cardiomyopathies caused by genetic abnormalities?
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
What is Marfan syndrome?
Autosomal dominated disease of the connective tissue
What is the chromosomal abnormality in Marfan syndrome?
Mutation in the fibrillin 1 gene on chromosome 15q21
What is the criteria used to diagnose Marfan syndrome?
Ghent 2010 criteria - 2 system findings must be positive
What are the cardiovascular features of Marfan syndrome?
Aortic dilatation or dissection
What condition of the eyes is caused by Marfan syndrome?
Ectopia lentis
What features are involved in the systemic score of Marfan syndrome?
Must score >= 7: Skeletal Skin Respiratory Dural ectasia Mitral valve prolapse
What features are involved in the FH of Marfan syndrome?
Affected relative
What are the genetic features of Marfan syndrome?
Fibrillin 1 mutation
What are the skeletal features of Marfans included in the systemic score?
ULSR and SHR Scoliosis/kyphosis Pectus deformity Thumb and wrist Foot/ankle Reduced elbow extension < 170
What are other features of Marfan syndrome which is included in the systemic score?
Pneumothorax
Striae
Protusio acetabula
Myopia
Is the condition Marfan syndrome if the systemic score is >= 7?
Yes
What is the condition if the systemic score for Marfan syndrome is >= 5?
MASS - Mitral valve prolapse, Aortic root diameter at upper limits of normal for body size, Stretch marks of the skin, and Skeletal conditions similar to Marfan syndrome. It is caused by a mutation in the FBN1 gene
What investigations should be used for Marfan syndrome?
Echo
MRI and/or pelvic X-ray (when a positive result would change diagnosis)
What can an echo show in a patient with Marfan syndrome?
Dural ectasia (92% of patients) Protusio acetabula
When should genetic testing be carried out for suspected Marfan case?
When a positive result would change the diagnosis (1 major and 1 minor or 2 major criteria)
What is the management of Marfan syndrome?
At least annual review
Echo
B blockers
Prophylactic aortic surgery if sinus of vaxsalva > 5.5.cm
Monitor aortic root freq in pregnancy if > 4cm
What is Long QT syndrome?
Condition which affects repolarisation of the heart after a heartbeat
What can Long QT Syndrome cause?
Syncope
Seizure (when brain starved of O2)
Sudden death
What are exacerbating factors of long QT syndrome?
Drugs
Emotion
Exercise
What test can diagnose Long QT syndrome?
ECG
What irregularity of the heart beat can be cause in Long QT syndrome?
Proxysmal polymorphic ventricular tachycardia - as heart is taking longer to repolarise, so a new contraction might be initiated before than last one finished
In what genes are mutations looked for in genetic testing for LQT?
KCNQ1
KCNH2
SCN5A
What is the treatment for LQT?
Beta blockers, nicrorandil
Mexilitene, lidocaine, ICD
What is Brugada syndrome?
RBBB
QT normal
ST elevation V1-3
How is Bruguda syndrome managed?
With rest and sleep
What gene is though to be abnormal in bruguda syndrome?
SCN5A
What is ARVC?
Arrhythmogenic right ventricular cardiomyopathy (ARVC) - a rare inherited disease of the heart muscle
What are the features on an ECG in ARVC?
T wave inversion V2-3 on rest
Effort inducted polymorphic tachycardia (LBBB)
What gene abnormalities cause the disordered cell junction of ARVC?
Plakophilin 2
Desmoglein 2
Desmoplakin
What investigations should be carried out for ARVC after the ECG?
Echo to show features of dilated cardiomyopathy
Genetic testing: LMNA SCN5A
What is used to diagnose ARVC?
History of pre-syncope with tachy or brady or arrhythmia on ECG
FH of cardiomyopathy
What is cascade screening?
Mechanism for identifying people at risk for a genetic condition by a process of systematic family tracing
Why can cardiac phenotypic and genetic testing be useful?
Prevention of avoidable morbidity and mortality
What is Cryptorchidism?
A condition in which one or both of the testes fail to descend from the abdomen into the scrotum.
