Genetic Vascular Diseases

Question 1

What is the gene for Marfan?

Answer 1

FBN1 (fibrilin 1)

Question 2

What are the cardiac manifestations of Marfan syndrome?

Answer 2

• aortic root dilation/aneurysm (when the first section of the aorta, where the aortic valve resides, becomes enlarged. When this enlargement reaches a critical size, there is a risk of it rupturing or tearing)
• aortic dissection (tear in tunica intima leading to blood invading space between tunica intima and media of the arota)
• other arteries can be involved
• Mitral and tricuspid valve prolapse is
  common

Question 3

What is mitral valve prolapse?

Answer 3

• mitral vavle separates the L atrium and L ventricle
• if not closing all the way leads to mitral regurgitation - blood goes back from L ventricle to L atrium instead of out the aorta when the mitral valve is supposed to be closed
• can be caused by connective tissue unable to hold valve in place
• can be cause of herat murmur
• can lead to left sided heart failue
• chordae tendineae aka heart strings which connect the papillary muscles in the heart to the mitral valve can be affected by Marfan syndrome

Question 4

What is tricuspid valve prolapse?

Answer 4

• separates R atrium from R ventricle
• regurgitation happends when the valve doesn’t close all the way and blood flows back from R ventricle to R atrium
• chordae tendineae aka heart strings which connect the papillary muscles in the heart to the tricuspid valve can be affected by Marfan syndrome
• can lead to right sided heart failure

Question 5

What is a prolapse?

Answer 5

A bulging or falling out of a body part, such as the rectum or vagina, that commonly occurs because of weakened supportive tissues.

Question 6

During systole the mitral and tricuspid valves ?

Answer 6

close

Question 7

During diastole the mitral and tricuspid valves ?

Answer 7

• open
• diastole = relaxation and filling
• allows for filling of ventricles

Question 8

Haploinsufficiency of FBN1 leads to ?

Answer 8

reduced fibrillin content in the elastic layers of the arteries, resulting in decreased elasticity and integrity

Question 9

An FBN1 variant without Marfan syndrome diagnosis can lead to singular findings such as…

Answer 9

• lenticular dislocation
• aortic root dilation

Question 10

What does Loeys-Dietz Syndrome often look like?

Answer 10

Marfan syndrome

Question 11

What are the distinguishing features of Loeys-Dietz Syndrome from Marfan Syndrome?

Answer 11

• no lenticular dislocation
• bifid uvula
• hand deformities
• hypertelorism
• craniosynostosis

Question 12

Is Loeys-Dietz Syndrome or Marfan Syndrome considered more severe?

Answer 12

Loeys-Dietz Syndrome
* extra-aortic blood vessels are more concerning in LDS than in Marfan’s

Question 13

Genes involving which pathway are affected in Loeys-Dietz Syndrome?

Answer 13

TGFβ-signaling pathway

Question 14

Which genes are assocaited with Loeys-Dietz Syndrome?

Answer 14

SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1,TGFBR2

Question 15

Which gene is implicated in the vascular type
of the Ehlers-Danlos syndrome?

Answer 15

COL3A1

heterozygous

Question 16

What are the cardiac assocaited risks for vascular EDS?

Answer 16

• arterial aneurysm
• arterial dissection
• arterial rupture

high morbidity and mortality rate

Question 17

What visceral clinical manifestations are seen in vEDS?

Answer 17

• organ prolapse (uterine,
  rectum, bladder)
• intestinal rupture

Question 18

Aortic aneurysm is also associated with EDS gene variants in which genes?

Answer 18

• PLOD1
• FKBP14
• TNXB

homozygous or compound heterozygous = PLOD1 & FKBP14 which are the kyphoscoliotic forms of EDS
TNXB = classic-like EDS

Question 19

Why do people with vEDS sometimes fly under the radar?

Answer 19

not as flexible as other types of EGS

Question 20

What is familial thoracic aortic aneurysm and dissection (FTAAD)? What genes?

Answer 20

• non-syndromic form of aortopathies (vs Marfan, LDS, and vEDS)
• smooth muscle cell dysfunction
• genes: ACTA2, MYH11, MYLK, PRKG1

Question 21

What heart defect is associated with Williams Syndrome?

Answer 21

supravalvular aortic stenosis

Question 22

What microdeletion and gene are assocaited with Williams Syndrome?

Answer 22

• 7q11.23
• ELN

Question 23

Heterozygous loss of function variants in the gene for ? results in a high risk for supravalvular aortic stenosis

Answer 23

elastin (ELN)

Question 24

What syndromes are associated with aortic coarctation?

Answer 24

• Turner syndrome
• Noonan syndrome
• Alagille syndrome
• isolated/non-syndromic

MYH6 = genetic cause for isolated cases

Question 25

Which heart anomalies are associated with Turner syndrome?

Answer 25

• coarctation of aorta
• bicuspid aortic valve (should be tricuspid)

Question 26

Bicuspid aortic valve (should be tricuspid) is associated with one syndrome and one genetic variant, what are these?

Answer 26

• Turner syndrome
• NOTCH1 gene

treatment: valve replacement & aortic root reconstruction

Question 27

Primary Pulmonary Arterial Hypertension (PPAH) a rare
genetic disorder due to intrinsic proliferation of pulmonary smooth muscle, leading
to the manifestation of pulmonary arterial hypertension immediately after birth. What will patients with this disorder present with?

Answer 27

• repiratory distress
• cyanosis
• signs of right ventricular strain and failure
• high rate of morbidity and mortality

will prsent at birth w/ these symptoms

Question 28

Primary Pulmonary Arterial Hypertension (PPAH) is associated with many genes, but one gene accounts for about 70% of cases. What is that gene?

Answer 28

BMPR2