Genetics

Question 1

PKP2 genetic mutation is associated with..

Answer 1

Arrythmogenic cardiomyopathy (ARVC)

Question 2

Most common inheritance pattern of dilated CM

Answer 2

Autosomal dominant

Question 3

What is Barth Syndrome?
- Inheritance pattern
- Findings

Answer 3

Inheritance- X linked recessive, mutation in TAZ gene
Findings: Dilated CM or non-compaction CM
Other findings: Hypotonia, short stature, proximal muscle weakness, neutropenia, abnroaml 3-methylglutaconic aciduria

Question 4

What two genes account for 75% of familial sarcomeric HCM?

Answer 4

MHY7 and MYBPC3

Question 5

Most common RASopathy associated with HCM

Answer 5

Noonan syndrome

Question 6

Beside HCM, what other CHD can patients with Noonan syndrome develop?

Answer 6

Pulmonic stenosis

Question 7

Name 3 genes that are associated with RASopathies

Answer 7

PTPN11
RAF1
RIT1

Can think of Josh saying “quit it with the rit raf!!”

Question 8

Most common mutation associated with Noonan

Answer 8

PTPN11

Question 9

Most common gene mutation associated with inherited DCM

Answer 9

TTN (5-25%)

Question 10

Inheritance pattern of dystrophinopathies

Answer 10

Mostly X linked

Question 11

Describe the etiology of the different presentations of Duchenne vs Becker DCM

Answer 11

Duchenne: absence of the dystrophin gene
Becker: some dystrophin gene, short and partial function

Question 12

Emery-Dreifuss MD: What genes are associated?

Answer 12

EMD and FHL-1 (x linked)
LMNA (AR and AD)

Proteins involved in the nuclear membrane of the myocytes

Question 13

What clinical features are present with Emery-Driefuss MD?

Answer 13

Cardiac: DCM > HCM, conduction abnormalities and arrhythmia
Non-cardiac: Contractures and progressive weakness/wasting

Question 14

Gene associated with increased risk of SCD in patients with Limb-Girdle MD?

Answer 14

DES mutations

Question 15

What three genes in muscular dystrophies are associated with increased arrhythmia risk?

Answer 15

EMD, LMNA, and DES

Question 16

What are the clinical findings of 1p36 deletion syndrome?

Answer 16

Small head, deep eyes, straight eyebrows, midface hypoplasia, developmental delay

+ DCM, LVNC and a slew of other CHD - ASD. VSD, PDA, PS, BAV, etc.

Question 17

What two syndromes are associated with LV non compaction CM?

Answer 17

Barth’s (also DCM)
1p36 microdeletion (also DCM)

Question 18

What is the inheritance pattern of most inborn errors of metabolism?

Answer 18

AR

Question 19

Name two mitochondrial inborn errors of metabolism

Answer 19

MELAS : Mitochondiral encephalopathy, lactic acidosis and stroke
Kearns-Sayre: Cranial and opthalmologic

Question 20

What is the clinical presentation of Kearns Sayre?

Answer 20

(mitochondrial deletion)
Age < 20
Progressive opthalmoplegia
Pigmentary retinopathy
Progressive heart block 2/2 degeneration of the conduction system

Question 21

What is a common presentation of a fatty acid oxidation defect and what is an example?

Answer 21

Acute decompensation after fasting
Hypoglycemia, metabolism acidosis, hyperammonia, abnormal acyl carnitine profile

Example: CPT2

Question 22

Pompe disease: What is the official name? What gene is involved?

Answer 22

Official name: glycogen storage disease II
Gene involved: GAA

Question 23

Dannon disease: What gene is involved? How can you differentiate clinically from Pompe?

Answer 23

LAMP2
Will have normal values of alpha acid gluconidase levels

Question 24

Why. is the PR interval important in pompe?

Answer 24

Progressive accumulation of glycogen in the conduction system > increased PR > increased risk of SCD

Question 25

Name 2 lipid storage diseases associated with CM

Answer 25

Gaucher and Fabry

Question 26

Describe the cardiovascular subtype of gaucher

Answer 26

glucocerebrosidase deficiency Calcification of mitral and aortic valve mutation in GBA

Question 27

Describe clinical manifestations of Fabry

Answer 27

x-linked, GLA mutation Severe extremity pain Corneal involvement Renal failure Conduction abnormalities + HCM

Question 28

Name the syndrome: coarse facial features, short, severe HSM, thickened leaflets resulting in regurg

Answer 28

mucopolysaccharide storage dx Hurler (AR) and hunter (X linked) Hunter does not have corneal clouding

Question 29

CAVC, low tone, upslanting palpebral fissures, advanced maternal age

Answer 29

T21

Question 30

Polyvalvar disease, clenched hands with overlapping fingers, nail hypoplasia, low set ears, small mouth

Answer 30

Edward syndrome (T18)

Question 31

Orofacial clefts, microphthalmia/anoph thalmia, postaxial polydactyly, holoproscencephaly

Answer 31

Trisomy 13 (Patau)

Question 32

Inheritance pattern of the Trisomies

Answer 32

AD although the VAST majority are denovo mutations

Question 33

Female with short stature, left-sided lesions

Answer 33

Turner syndrome

Question 34

What cardiac lesions are seen with Turner syndrome?

Answer 34

Left-sided lesions - CoA - BAV/AS - HLHS - mitral valve prolapse - aortic root dilation/dissection Pulmonary vein anomalies Prolonged QTc

Question 35

Interrupted aortic arch type B, conotruncal defects, absent thymus, hypocalcemia

Answer 35

DiGeorge (22q11)

Question 36

Supravalvar aortic stenosis, stellate irises, short stature, hoarse voice, unique cognitive profile

Answer 36

Williams syndrome

Question 37

Cardiac lesions seen in Williams syndrome

Answer 37

Supravalvar AS Supravalvar PS Peripheral pulmonary artery stenosis Arteriopathy

Question 38

Syndrome with HLHS

Answer 38

Jacobsen syndrome

Question 39

What is the best genetic testing for STRUCTURAL VARIATION / COPY NUMBER VARIATION / MICRODELETION SYNDROMES

Answer 39

Chromosomal microarray

Question 40

Cutis aplasia Syndrome with HLHS

Answer 40

Adams Oliver syndrome

Question 41

What is the best genetic testing for SINGLE GENE DISORDERS?

Answer 41

Gene sequencing - either targeted or whole genome

Question 42

PPS, triangular faces, butterfly vertebrae, cholestasis

Answer 42

Alagille syndrome

Question 43

What gene is mutated in Alagille syndrome?

Answer 43

JAG1

Question 44

Short stature, developmental delay, ear anomalies, coloboma, tetralogy of Fallot

Answer 44

CHARGE syndrome

Question 45

What gene is mutated in CHARGE syndrome?

Answer 45

CHD7

Question 46

Synophrys Long curled eyelashes VSD, ASD, PS

Answer 46

Cornelia De Lange syndrome

Question 47

Short stature, dental anomalies, polydactyly, common atrium

Answer 47

Ellis van Creveld (EVC mutations, AR)

Question 48

Upper extremity anomaly, absent thumb, common atrium, heart block, affected parent

Answer 48

Holt Oram

Question 49

What cardiac finding needs to be monitored in Holt Oram disease?

Answer 49

Progressive heart block

Question 50

What gene is mutated in Holt Oram disease?

Answer 50

TBX5

Question 51

Wide palpebral fissures with eversion of the lateral third of the lower eyelid Arched, broad eyebrows, left sided lesions

Answer 51

Kabuki syndrome

Question 52

What cardiac lesions can you see with Kabuki syndrome?

Answer 52

LSL: CoA, BAV, HLHS VSD TOF TGA

Question 53

Broad thumbs, “grimacing” smile Intellectual disability PDA or septal fect

Answer 53

Rubinstein-Taybi

Question 54

Pulmonic stenosis (thick/dysplastic valve), HCM, short stature, neck webbing, pectus, low set ears

Answer 54

Noonan

Question 55

Short stature, loose skin, multifocal atrial tachycardia

Answer 55

Costello syndrome

Question 56

Multiple café au lait spots, axillary and inguinal freckling, Cutaneous neurofibromas Iris Lisch nodues, CoA, PS

Answer 56

Neurofibromatosis 1 (no intracardiac masses)

Question 57

Gene mutation in Marfans

Answer 57

FBN1 (AD)

Question 58

Tall thin habitus with long armspan, scoliosis, thick glasses, pectus, aortic root dilation, mitral valve prolapse, ectopia lentis

Answer 58

Marfan

Question 59

Gene mutations (2) in Loeys Dietz

Answer 59

TGFBR1 TGFBR2

Question 60

Arterial aneurysms, tortuosity, aortic root dilation, widely spaced eyes, bifid uvula, pectus, BAV, PDA, club foot

Answer 60

Loeys-Dietz

Question 61

Marfan's appearance, Crumpled ears, joint contractures at birth, scoliosis, aortic root dilation

Answer 61

Congenital Contractural Arachnodactyly (Beals)- FBN2

Question 62

TV prolapse, MV prolapse AoR dilation (not progressive) Arterial rupture (very rare)

Answer 62

EDS classic

Question 63

What gene is involved in Ehler Danlos?

Answer 63

COL

Question 64

Dextrocardia, bronchiectasis, nasal polyps

Answer 64

Kartagener, Primary ciliary dyskinesia

Question 65

Inheritance of Kartagner's disease

Answer 65

AR

Question 66

Cardiac rhabdomyoma, skin findings, infantile spasms

Answer 66

Tuberous Sclerosis

Question 67

Williams syndrome has a mutation in what chromosome?

Answer 67

7q11

Question 68

Cru-de-chat syndrome is caused by what?

Answer 68

Deletion on chromosome 5 5p- syndrome

Question 69

What trisomy has the highest rate of CHD?

Answer 69

T18 - 95% chance of CHD

Question 70

What connective tissue diseases has the risk of aortic dissection?

Answer 70

Marfans and LD ED does not

Question 71

What condition can appear like Marfans but is associated with intellectual delay?

Answer 71

Autosomal recessive homocystienuria

Question 72

What cardiac lesions is maternal PKU associated with?

Answer 72

Primarily left sided lesions - HLHS, coarctation