Marfan Syndrome – causes, symptoms, diagnosis, treatment, pathology

Marfan Syndrome – causes, symptoms, diagnosis, treatment, pathology

Marfan syndrome is a genetic disorder that
results in defective connective tissue, which can affect a person’s skeleton, heart, blood
vessels, eyes, and lungs. Normally, the interstitial space of various
body tissues is full of microfibrils – which are strong ropelike structures that provide
tissue integrity and form connective tissue. The main component of microfibrils is a glycoprotein
called fibrillin. In some structures microfibrils form a scaffold
for additional proteins like elastin. Elastin fibers are highly cross-linked, and
that gives them a rubber-band-like quality, which allows tissues to stretch and then spring
back to their original shape. Tissues that have elastin fibers are tissues
like the arteries, skin, and lungs, and tissues that have microfibrils but no overlying layer
of elastin are like tendons and the ciliary zonules that hold the eye lens in place. These tissues are less stretchable, but still
have considerable tensile strength. In addition to being part of microfibrils,
fibrillin also regulates tissue growth. Fibrillin sequesters or removes transforming
growth factor beta, or TGF-β, which stimulates tissue growth, so fibrillin therefore lowers
how much TGF-β is available to stimulate growth. Marfan syndrome is caused by mutations in
a gene called FBN1, or fibrillin 1, on chromosome 15. It’s autosomal dominant, which means that
even if there’s a normal copy of the gene, a single mutated copy of the gene – in other
words a heterozygous mutation – is sufficient to cause the disease. The FBN1 gene encodes Fibrillin-1 protein,
one of three fibrillin subtypes. In Marfan syndrome, fibrillin-1 is either
dysfunctional or less abundant. As a result, there are fewer functioning microfibrils
in the extracellular matrix, and that means there’s less tissue integrity and elasticity. Connective tissue is found throughout the
body, so this can affect nearly every body system. Additionally, TGF-β doesn’t get effectively
sequestered, so TGF-β signaling is excessive in these tissues – meaning more growth. The most obvious physical features of Marfan
syndrome involve the skeleton. The long bones grow excessively, so individuals
are tall with long arms and legs – this is called a Marfanoid body habitus. They have long, thin fingers and toes too,
called arachnodactyly, which is a reference to the long legs of spiders. Finally, overgrowth of ribs can cause pectus
excavatum, where the chest sinks in, or pectus carinatum, where the chest points out. Other bone and joint features include scoliosis
where the spine has a sideways curve, an inability to extend the elbows all the way to 180 degrees,
flexible joints, a downward slant to the eyes, and a narrow palate that crowds the teeth. In the skin, Marfan syndrome can cause stretch
marks, and in the lung it can cause bullae to form. Which are large spaces that replace the normal
architecture of the lungs and can cause a pneumothorax to form. In the eyes, Marfan syndrome is a risk factor
for retinal detachment and a dislocation of the lens, which is usually in an upward direction. The most serious features, though, of Marfan
syndrome are cardiovascular. The aorta dilates over time, which is a risk
for aortic valve insufficiency, where blood leaks back into the left ventricle during
diastole. The aorta also undergoes cystic medial necrosis,
which is where there is degeneration of the tunica media, which is the central portion
of the aortic wall. Both dilation and cystic medial necrosis weaken
the aorta, making it susceptible to aneurysm, dissection, and rupture. An aneurysm is an outpouching of a vessel,
which weakens its wall even further. A dissection is where the inner wall, or intima,
gets a tear, and blood tracks into a false lumen in the vessel wall. And this can occlude normal blood flow. An aortic rupture is a full-thickness tear,
which allows blood to escape the vessel. And all of these complications can be fatal. Finally, Marfan syndrome is a risk factor
for mitral valve prolapse, where the mitral valve pouches into the left atrium during
systole. The features of Marfan syndrome, though, might
not be present for everyone with Marfan syndrome, and any given feature can be more or less
severe. Also, Marfan syndrome isn’t usually noticeable
at birth, so the symptoms show up over time as the child grows. Occasionally, though, features are present
at birth, called early-onset or neonatal Marfan syndrome. As for diagnosis, A person is diagnosed with
Marfan syndrome if they have clinical features of Marfan syndrome like aortic disease, a
dislocated lens, family history, and FBN1 mutations. Now, although there is no cure for Marfan
syndrome but there are treatments for some of the clinical features. For example, if an eye lens dislocates, it
can be removed and replaced by an artificial lens. If the aorta gets too wide, it can be repaired
surgically so it doesn’t dissect or rupture. Beta blockers have been shown to slow aortic
dilation, and the angiotensin receptor blocker losartan, which decreases TGF-β signaling,
can slow dilation even more when given in conjunction with a beta blocker. All right, as a quick recap -Marfan syndrome
is an autosomal dominant genetic disorder caused by mutations in the FBN1 gene. This leads to fewer fibrillin microfibrils
in certain connective tissues, which compromises their strength and elasticity, and upregulating
TGF-β signaling. The end result is an individual with a tall,
thin body with symptoms of loose connective tissue, most importantly in the aorta.

49 Replies to “Marfan Syndrome – causes, symptoms, diagnosis, treatment, pathology”

  1. i have marfan 😭😭i cant gain weight im eating eating but idk 😐… its so sad 😞 because i cant wear what i want, sometimes i want kill myself, people thinks i have anorexia

  2. I’m 6’ 1” but I’m only 129lbs, my arms, fingers, and legs are very long( my wingspan is 4.5 inches longer than my height) I’ve been much skinner and taller than many of the people I knew since elementary school (I’m 15 now btw) while I display these symptoms, I don’t have scoliosis, eye or heart problems to my knowledge. Would it still be a good idea to see if I have Marfan syndrome?

  3. Actually and sadly, even today a lot of Dr.s aren’t familiar w this syndrome… a lot of the time, they don’t find out til a family member has died and they test you, or u til after you have died. If you have any of these characteristics, go to a specialist and get tested!

  4. I have that my doctors in swedens say that i can grow 2.4m if i dont take opration on my legs😓 and i am 13

  5. To all of those people who have Marfan Syndrome. I dunno, maybe, my thoughts could be useful at this point. You know, I have this syndrom since I was born (well, obviosly), and I hated myself for that for the long years. Now I have perfect legs with muscles, ugly thin arms, a quite big belly and a hanchback. My eyesight is minus 21, I have got a scoleosis of the third type, and I had a surgery on my heart. I look like a bad joke of Mother-Nature. And you know what? Now, if I could
    completely heal myself, I, probably, would not, Because the truth is: we ARE very talanted folks. U know, I think, we all (Marfanists, I mean) should do some art, especially music. I would not change my long fingers and my brain (sometimes stupid, sometimes brilliant) for the averege ones. So that is it.)) Sorry for my bad English – I am not native-speaker. Thanks

  6. After 15 years of these kind of issues coming up, I was finally diagnosed with this a few weeks ago. Now I wish to know more about it. Thanks for the informative video!

  7. I have horrible eyesight since i can remember, pectus excavatum, and am 6ft but i’m always told im long and i look very slender compared to everyone else and i’ve always been told this. i’m always told my legs are long, my pants size is 29/32 and i thought i was jus kinda tall but people always say i got long legs. i eat a lot and can never gain weight and i try so hard but my posture is always bad but even if i poke my chest out i still look weird. i had crooked teeth but then i got braces and they took two teeth out. should i be concerned ?

  8. I have a friend with long ass limbs and a sunken chest and hes tall, hes on my football (american) team and also plays basket ball, I think he has this

  9. are there people who have marfan syndrome by growing normally without symptoms? because my baby is suspected of being Marfan by a doctor

  10. I'm going through the stages of being diagnosed with this I pray to God I don't have this because if I do I won't no what to do with myself

  11. That small explanation is simply fantastic and mind blowing. So simple yet so informative. You have no idea, what a great job you are doing for the future doctors. Thank you so much for every video

  12. Im 13 years old, I hae scoliosis, my wingspan is bigger than my height and I have pectum scavatus. But my heart is great, my lungs are fine,(I cant breathe very well because I have rhinitis) and my eyes are okay, except for the fact I have a ball on my eyes. Im not that tall. 1,70 and Im 13. Im also not that skinny. Im not sure if I have it or not

  13. I am doing a research project on this in Biology class. This is helpful. I actually have a similar disorder Elhers Danlos Syndrome which has a lot of the same symptoms, except we look average, and it effects the joints more severely.

  14. you know how it feels when i search for any syndrome or explanation and find osmosis explaning the same thing, what a relieeeeeef 😍😍😍

  15. I have marfans but the only thing that isnt normal is my heart, if it gets worse I will need surgery, hope it wont get worse

  16. Went out with a man with Marfrans years ago "Tree"🙃 6ft7in skinny etc. Didn't realise that he had a pacemaker and said that he had a really loud watch!! Lol
    Ended up taking a spill on the bike. He received a bung knee and it kind of went down hill from there. Aorta broke from the pacemaker. Got gangrene in his gut and sadly passed away. Late 30s.
    He had a lived a great life. Loved to build his Harley's and loved his "brothers" and Me and Bobby Magee. I was very lucky to share his last ride. Peace

  17. I have a very, very, VERY weird question to ask

    Do marfanoid men have long ds? Not trying to be perverted, but I'm curious.

  18. I'm afraid I have this. I have a windswept deformity in my knees and legs. I'm a little concerned.

  19. My boyfriend has Marfans. I am learning more about it to understand it. He’s explained to me a little but I just wanna know more to understand him better. This video has helped me with my notes 🙂 ty!

  20. You guys should listen to second and Sebring. It's about his mother dying of this when he was 17. Wait nevermind that insensitive. I'm so sorry.

Leave a Reply

Your email address will not be published. Required fields are marked *