Genetic and Cardiovascular Disease Flashcards by Chloe Lee

Name some causes of congenital heart disease

Chromosomal 
Microdeletions 
Single gene 
Teratogens 
Other 
Multifactorial

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What abnormalities of chromosomes can cause a congenital heart disease?

Trisomies/monosomies

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What congenital heart diseases can be caused by microdeletions?

22q11 (DiGeorge)

Williams

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What congenital heart disease can be caused by single gene abnormalities?

Noonan

Marfan

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Name 3 teratogens

Rubella
Alcohol
Anti-epileptic drugs

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What is the chromosomal abnormality in Down Syndrome?

Trisomy 21 - extra chromosome due to maternal non-disjunction

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What defects are associated with Down syndrome?

Atrio-ventricular septal defect (15%)

Duodenal atresia

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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

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How does the risk of Down syndrome change with increasing maternal age?

Increases risk

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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

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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

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What is the chromosomal abnormality in Turner Syndrome?

Incomplete X chromosome (45, X) - therefore they develop as females

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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

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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)

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Why does neck webbing arise in CHD?

Due to excess nuchal folds

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What syndromes does neck webbing occur in?

Turner 
Noonan
CFC
Leopard
Costello

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What defects are associated with Noonan syndrome?

Pulmonary stenosis 
Short stature 
Neck webbing 
Cryptorchidism 
Characteristic face

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What type of chromosomal mutation causes Turner syndome?

Monosomy

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What type of chromosomal mutation causes Down syndrome?

Trisomy

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What is the gene affected in Noonan syndrome?

PTPN11 gene

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What are the features of cardio-facio-cutaneous (CFC) syndrome?

Noonan-like appearance
Ectodermal problems
Developmental delay

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What are the features of Leopard syndrome?

Noonan-like appearance
Multiple lentigines
Deafness

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What are the features of Costello syndrome?

Noonan-like appearance 
Thickened skin folds
Susceptibility to warts
Cardiomyopathy 
Cancer risk in later life

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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

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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.