Genetic Vascular Diseases Flashcards
What is the gene for Marfan?
FBN1 (fibrilin 1)
What are the cardiac manifestations of Marfan syndrome?
- 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
What is mitral valve prolapse?
- 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
What is tricuspid valve prolapse?
- 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
What is a prolapse?
A bulging or falling out of a body part, such as the rectum or vagina, that commonly occurs because of weakened supportive tissues.
During systole the mitral and tricuspid valves ?
close
During diastole the mitral and tricuspid valves ?
- open
- diastole = relaxation and filling
- allows for filling of ventricles
Haploinsufficiency of FBN1 leads to ?
reduced fibrillin content in the elastic layers of the arteries, resulting in decreased elasticity and integrity
An FBN1 variant without Marfan syndrome diagnosis can lead to singular findings such as…
- lenticular dislocation
- aortic root dilation
What does Loeys-Dietz Syndrome often look like?
Marfan syndrome
What are the distinguishing features of Loeys-Dietz Syndrome from Marfan Syndrome?
- no lenticular dislocation
- bifid uvula
- hand deformities
- hypertelorism
- craniosynostosis
Is Loeys-Dietz Syndrome or Marfan Syndrome considered more severe?
Loeys-Dietz Syndrome
* extra-aortic blood vessels are more concerning in LDS than in Marfan’s
Genes involving which pathway are affected in Loeys-Dietz Syndrome?
TGFβ-signaling pathway
Which genes are assocaited with Loeys-Dietz Syndrome?
SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1,TGFBR2
Which gene is implicated in the vascular type
of the Ehlers-Danlos syndrome?
COL3A1
heterozygous
What are the cardiac assocaited risks for vascular EDS?
- arterial aneurysm
- arterial dissection
- arterial rupture
high morbidity and mortality rate
What visceral clinical manifestations are seen in vEDS?
- organ prolapse (uterine,
rectum, bladder) - intestinal rupture
Aortic aneurysm is also associated with EDS gene variants in which genes?
- PLOD1
- FKBP14
- TNXB
homozygous or compound heterozygous = PLOD1 & FKBP14 which are the kyphoscoliotic forms of EDS
TNXB = classic-like EDS
Why do people with vEDS sometimes fly under the radar?
not as flexible as other types of EGS
What is familial thoracic aortic aneurysm and dissection (FTAAD)? What genes?
- non-syndromic form of aortopathies (vs Marfan, LDS, and vEDS)
- smooth muscle cell dysfunction
- genes: ACTA2, MYH11, MYLK, PRKG1
What heart defect is associated with Williams Syndrome?
supravalvular aortic stenosis
What microdeletion and gene are assocaited with Williams Syndrome?
- 7q11.23
- ELN
Heterozygous loss of function variants in the gene for ? results in a high risk for supravalvular aortic stenosis
elastin (ELN)
What syndromes are associated with aortic coarctation?
- Turner syndrome
- Noonan syndrome
- Alagille syndrome
- isolated/non-syndromic
MYH6 = genetic cause for isolated cases
Which heart anomalies are associated with Turner syndrome?
- coarctation of aorta
- bicuspid aortic valve (should be tricuspid)
Bicuspid aortic valve (should be tricuspid) is associated with one syndrome and one genetic variant, what are these?
- Turner syndrome
- NOTCH1 gene
treatment: valve replacement & aortic root reconstruction
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?
- repiratory distress
- cyanosis
- signs of right ventricular strain and failure
- high rate of morbidity and mortality
will prsent at birth w/ these symptoms
Primary Pulmonary Arterial Hypertension (PPAH) is associated with many genes, but one gene accounts for about 70% of cases. What is that gene?
BMPR2
