Genetics of Cardiac Disease Nov21 M1

Question 1

trisomy 21 malformations other than cardiac

Answer 1

anal, duodenal atresia

strabismus

Question 2

trisomy 21 mental characteristics

Answer 2

intellectual disability, very happy and social

Question 3

trisomy 21 % withcongenital abnormalities

Answer 3

40%

Question 4

trisomy 21 3 frequent congenital CVD

Answer 4

atrial and ventricular septal defects
common atrioventricular canal
patent ductus arteriosus

Question 5

free trisomy 21 def as opposed to other

Answer 5

free = 3 chrom 21
other = translocation

Question 6

2 causes of trisomy 21

Answer 6

translocation

non disjunction at meiosis 1 or 2

Question 7

deletion of 22q11: problems other than cardiac

Answer 7

hypoplasia of thyroid (hypoCa) or thymus (immune deficiency).
Malformations like cleft palate, kidney, etc.

Question 8

% heart malformations in 22q11 deletion

Answer 8

75%

Question 9

3 frequent congenital heart malform in 22q11 deletions

Answer 9

tetralogy of Fallot
ventricular septal defect
interrupted aortic arch

Question 10

Tetralogy of Fallot: 4 anomalies

Answer 10

malalignement VSD
Subvalvular or valvular PS
RV hypertrophy
Overriding aorta

Question 11

important consequence of hypoCa in 22q11 deletion

Answer 11

seizures

Question 12

22q11 inheritance

Answer 12

autosomal dominant (dominant bc is a deletion in one of a parent’s chrom 22)

Question 13

other name for 22q11

Answer 13

DiGeorge syndrome

Question 14

how diagnose DiGeorge

Answer 14

karyotyping + dysmorphic features

Question 15

cardiomyopathy from mt disorder: problems other than cardiac

Answer 15

hypoglycemia, high lactic acid, floppy baby, hearing loss

Question 16

cardiomyopathy from mt disorder: cardiac problem

Answer 16

hypetrophy, heart murmur

Question 17

general principle in mt disorder

Answer 17

expect to have 3 organs affected that aren’t connected

Question 18

5 steps in mt disorder investigation

Answer 18

1. general biochem workup
2. eval other organs
3. biochem genetic workup (plasma a.a, urine organic acids)
4. biopsy (specific to mt eval)
5. molecular testing (DNA panels and mtDNA)

Question 19

medication in cardiomyopathy from mt disorder

Answer 19

carnitine, riboflavin, coenzyme Q10

Question 20

problems making it important to follow in cardiomyopathy from mt disorder

Answer 20

special management during crisis, surgery, anesthesia. symptomatic treamtent. genetic counselling

Question 21

mitochondria and mtDNa numbers

Answer 21

5-10 mtDNA per mt

0-2000 mt per cell

Question 22

mt proteins # and origin

Answer 22

1600. more 90% from nucleus

Question 23

mtDNA role

Answer 23

37 genes. tRNA, proteins, rRNA

Question 24

RULES OF MTDNA GENETICS

Answer 24

Heteroplasmy
Mitotic segregation
Maternal inheritance

Question 25

heteroplasmy def

Answer 25

deleterious mutaitons in mtDNA affect some but not all mtDNA

Question 26

threshold effect in heteroplasmy

Answer 26

need minimal critical mutation load (80-90%) to get effect

Question 27

homoplasmic mtDNA mutation def

Answer 27

mutation in all the mtDNA

Question 28

why maternal inheritance in mt disorders

Answer 28

mitochondria in zygote come from mother

Question 29

cardiomyopathy bc of lysosomal storage disorder: cardiac prob

Answer 29

hypetrophy

Question 30

cardiomyopathy bc of lysosomal storage disorder: other than cardiac problems

Answer 30

acroparasthesias (tickling and numbness in extremities), proteinuria, cognitive delays, episodes of fever, abdo pain, kidney problem, corneal opacity, stroke, pain and fatigue, can't sweat

Question 31

name of cardiomyopathy bc of lysosomal storage disorder

Answer 31

Fabry disease

Question 32

Fabry disease frequency

Answer 32

RARE. 1 in 200 000

Question 33

Fabry disease inheritance

Answer 33

X-linked (males more severely affected)

Question 34

Fabry disease cause

Answer 34

defect of enzyme alpha-galactosidase and accum of specific substrates

Question 35

Fabry disease: why important to know about

Answer 35

treatment easy: enzyme replacement therapy

Question 36

why have hypertrophy in Fabry disease

Answer 36

enzyme not cutting substrate (lysosomal storage disorder) and have accum of substrate

Question 37

Noonan syndrome: problems other than cardiac

Answer 37

dev delay, cognitive problems (mild), increased heart silouhette, hearing and vision problem

Question 38

cause of Noonan syndrome

Answer 38

genetic defect in any gene of growth factor receptor pathway + signal transduction to change gnee transcr (ERK, MEK, Grb2, KRAS, ...)

Question 39

Noonan syndrome inheritance

Answer 39

autosomal dominant

Question 40

Noonan syndrome: cardiac defects (2)

Answer 40

hypetrophic cardiomyopathy, PS

Question 41

locus heterogeneity def

Answer 41

one situation can arise from mutaiton in diff loci (dif fgenes)

Question 42

locus heterogeneity saw in what (2)

Answer 42

Noonan syndrome | most of genetic cardiomyopathies

Question 43

3 type of cardiomyopathies (CM)

Answer 43

dilatative hypertrophic arrhythmogenic RV dysplasia (ARVD)

Question 44

dilatative CM # genes, role of proteins

Answer 44

30 genes. role in cardiac sarcomere, ion channels, dystrophin, etc.

Question 45

hypertrophic CM # assoc with what

Answer 45

assoc with syndromes

Question 46

hypertrophic CM non syndromic # genes

Answer 46

20

Question 47

ARVD CN # genes

Answer 47

7

Question 48

assessment of CM

Answer 48

- clinical (Echo, ECG, MRI) - history + physical - cumul phenotype info

Question 49

Marfan syndrome systems involved

Answer 49

skeletal, cardiac, ocular

Question 50

cardiac prob in Marfan

Answer 50

dilatation, dissection of ascending or descending thoracic or abdominal aorta

Question 51

cause of Marfan

Answer 51

mutation in fibrillin 1

Question 52

Marfan inheritance

Answer 52

autosomal dominant

Question 53

Marfan genetic mechanism

Answer 53

dominant negative

Question 54

2 differentials of Marfan

Answer 54

Loeys-Dietz syndrome (aortic prob, more aggressive treatment) Homocystinuria (diet restriction, meds)

Question 55

Marfan treatment

Answer 55

beta blockers, aortic surgery, no contact sport

Question 56

fibrillin function

Answer 56

glycoprotein part of cytoplasm structure linking complex with gene TGF factor

Question 57

prob with fibrillin mutation

Answer 57

neg effect on structure with TGF. gin of function. complex does diff function, pthway overstimulated

Question 58

3 types of genetic heart disease

Answer 58

heart malformation, hypertrophic CM, vascular disease

Question 59

5 genetic causes of genetic heart disease + particular one

Answer 59

abnormal # chrom (ONLY heart malformations), microdeletions, single gene mutation, mt disorder, lysosomal storage