Genetic Cardiac Disease Flashcards Preview

Cardiovascular System > Genetic Cardiac Disease > Flashcards

Flashcards in Genetic Cardiac Disease Deck (29):
1

Connective tissue diseases

- Marfan
- Loeys-Dietz
- Ehlers Danlos
- FTAA

2

Familial Arrhythmias syndromes

- Long QT
- Brugada
- CPVT
- ARVC

3

Familial Cardiomyopathy syndromes

- HCM
- DCM

4

Features of Marfan syndrome

- Autosomal dominant
- Multisystem
- Connective tissue
- Fibrillin 1 gene
- Chromosome 15q21
- TGFbetaR 2 (and TGFbetaR1)
- Chromosome 3p22 (9q33)

5

Physical features of Marfan syndrome aged 13

- Tall stature/pectus carinatum/ arachnodactyly
- Lens subluxation
- Mild aortic root dilatation

6

Physical features of Marfan syndrome aged 5

- Tall stature/pectus carinatum/ arachnodactyly
- Aortic root at upper limit of normal
- Father died aortic aneurysm

7

Findings of Ghent 2010 for diagnosis of marfan

Cardiovascular system
- Aortic dilatation/dissection

Eyes
- Ectopia lentis

Systemic score >7
- Skeletal
- Skin
- Respiratory
- Dural ectasia
- Mitral valve prolapse
- Myopia

Family history
- Unequivocally affected relative

Fibrillin 1
- Mutation known to cause MFS

8

Features of Marfan in childhood (features are age varying)

- Tall stature
- Pes plenus
- Pectus
- Scoliosis
- Face/palate
- Myopia
- Ectopia lentis
- Aortic
- Striae (stretch marks)

9

Mechanism of TGFb and fibrillin in Marfan in transgenic mice

- TGFb and fibrillin are both secreted into the extra-cellular matrix and interact in vitro
- Incorporation of fibrillin into microfibrils results in proteolytic release of TGFb
- TGFb signalling affects cell proliferation, differentiation and apoptosis
- Transgenic mice, deficient in Fibrillin have excess TGFb signalling and Marfan features
- TGFb antibodies, or the TGFb antagonist Losartan rescue the Marfan phenotype in Fibrillin deficient mice

10

Optimal management methods of Marfan

At least annual clinical review
- Echocardiogram
- Beta blockers
- Angiotensin II receptor blockers
- Prophyllactic aortic surgery if sinus of valsalva exceeds: 5.5cm or 5% growth per year (2mm in adults)
- Monitor aortic root frequently in pregnancy if diameter exceeds 4cm

11

What are Marfan - like syndromes?

- Loeys-Dietz syndrome
- Familial thoracic aortic aneurysms
- BAV/FTAA
- MASS phenotype

12

Features of Loeys-Dietz syndrome

- Arterial dissection, tortuosity, bifid uvula/cleft palate, hypertelorism, skin and skeletal findings
- TGFBR1/2, SMAD3, TGFB2, TGFB3

13

Features of Familial thoracic aortic aneurysms

- 29 gene TAAD gene panel
- TGFBR2, MYH11, ACTA2, SMAD3, COL3A1

14

Features of BAV/FTAA

- Bicuspid aortic valve/familial thoracic aortic aneurysm
- NOTCH1

15

Features of MASS phenotype

- Myopia, mitral valve prolapse, mild aortic dilatation (<2sd), striae, minor skeletal involvement
- Fibrillinopathy

16

What are long QT syndromes?

- Romano-Ward syndrome
- Jarvell Lange-Neilsen

17

Features of Romano-Ward syndrome

- Syncope "seizure", sudden death
- Emotion, exercise, drugs
- ECG shows prolonged QTc interval
- Repolarisation anomalies (T/U waves)
- Paroxysmal Polymorphic VT (Torsade de Pointes)

18

What is Bazett's formula?

QTc = QT/ Sqaure root of RR

19

Features of Jarvell Lange-Neilson syndrome

Same as Romano-Ward syndrome but + congenital sensorineural deafness

20

Know genotype predictions: precipitants of arrthymia and mutations associated with them

and Patterns on ECGs

21

Which conditions should be excluded from dilated cardiomyopathy?

- Ischaemic heart disease (angiography)
- Hypertension
- Skeletal muscle disease (neurology/genetics evaluation, CPK)
- Alcohol abuse (history and biochemical evidence, but 9% have TTN mutation)
- Exposure to cardiotoxic drugs (history)
- Haemochromatosis (ferritin/genotyping)

22

In dilated cardiomyopathy, when should mitochondrial disease be considered?

If there is:
- Diabetes
- Deafness
- Retinitis pigmentosa - Skeletal muscle disease
- Growth retardation
- Cognitive disorder

23

Testing techniques in genomics

- Whole genome sequencing
- Whole exome sequencing
- Software filtering

24

Diagnosis methods of Inherited Cardiac Conditions

- Diagnosis in proband: cardiac phenotype, genetic testing
- Family history
- Assess relatives
- Cascade screening of relatives
- Prevention of avoidable morbidity and mortality

25

What is the largest gene in the genome?

Titin
- 363 exons, 38138 amino acids

26

Features of Brugada syndrome

- SCD or VF/VT and Type 1Brugada ECG
- Prolonged PR interval
- Enlarged LV/poor LV function
- More common in young men especially of far eastern origin

27

Management of Brugada syndrome

- Avoid fever, excess alcohol
- Overeating (>vagal effects)
- ICD

28

2010 task force criteria of ARVC (Arrhythmogenic right ventricular cardiomyopathy)

- Ecgo/MRI (RV dyskinesia)
- ECG: epsilon waves, T wave inversion
- SAECG: late potentials
- Effort induced VT (LBBB)
- Histology: fatty infiltration of RV
- Family history/ pathogenic gene variant

29

What genes should genetic testing include in dilated cardiomyopathy?

- TTN
- LMNA
- MYH7
- MYBPC3
- TNNT2
- TNNI3
- SCN5A
and perhaps other genes such as dystrophin