Understanding Marfan Syndrome: Inheritance, Symptoms, and Management

hey guys it's Miracles this perfect snail is where medicine makes perfect sense let's continue our clinical

biochemistry playlist in previous videos we talked about the glycogen storage diseases we talked about sorbitol and

cataracts we discussed galactosemia and lactose intolerance we talked about the pancreatic eyelid cell tumors like

insulinoma gastroenoma somatostatinoma glucagonoma and even VIP Oma then we talked about cystinuria cystenosis

homocystinoria and now it's time for Marfan syndrome in some aspects it is similar to homocystinurium in others it

is way different that's why you need to pay close attention to the pattern of inheritance and the signs and symptoms

what do you call it when my fingers and toes are very long like this like a spider

arachnodactyly arachno means spider dactly means digits which includes finger and Toes please watch the videos

in this clinical biochemistry playlist in order Marfan syndrome is inherited in an autosomal dominant fashion which

means one of the parents is affected the other is unaffected so let's suppose that this is the mother and this is the

father can we do the Bonnet Square please big a small a that is affected small a small a that is normal big a

small a affected small a small a normal half of The Offspring are unaffected I.E normal half of them have the disease in

this case Marfan syndrome recall that in autosomal dominant diseases the uppercase a is the bad Gene but in

autosomal recessive diseases the lower case is the bad one normally speaking on your chromosome 15 there is a lovely

Gene known as fbn1 any Gene codes for what protein what's the name of the protein fibrillin one protein what's the

normal function of that normal protein 501 it has two functions it sequesters TGF beta transformational growth factor

beta what do you mean by sequester keep it in check keep it in jail not in the outside world and the other function of

fiber N1 is to cover and protect elastin which is an elastic protein in your connective tissue all of this was normal

but in Marfan syndrome there is a problem in the fbn1 gene on chromosome 15 which means 501 is toast which means

we cannot keep a TGF beta in check and that's why the level of TGF beta will go up because it has left the prison and

went to the outside world and I will be unable to protect elastin so I have elastin defect that's why they call it a

connective tissue disorder moreover more fan syndrome can have a lens subluxation or dislocation subluxation is when the

lens is still hanging by a thread but when the lens is completely dislodged floating freely we call this dislocation

and in Marfan syndrome the dislocation of the lens is upwards and outwards like this is the lens right now it has been

dislocated upwards and outwards superiorly and temporally and this is the exact opposite of homocystinuria

because the lens dislocation in homocystinuria was downwards and inwards inferiorly and nasally how do you

remember this medicosis do you have a mnemonic yes check out my upcoming video titled Marfan syndrome mnemonic you will

find it in this clinical biochemistry playlist in Marfan syndrome there is dilatation of the aortic root when you

dilate the aortic root the cusps will become far away from one another which means the valve will be unable to close

when it should be which means blood is gonna regurgitate if flow backwards the purpose of the aortic valve is to

prevent the back flow of the aortic blood back into the left ventricle but when I have aortic regurgitation I.E

insufficiency blood is going to regurgitate back into the left ventricle can this give me a murmur sure the

murmur of aortic regurgitation which is a diastolic decrease endometer best heard in the third left intercostal

space aortic regurgitation usually has a wide pulse pressure and this can get way worse during pregnancy due to increased

plasma volume and blood flow remember that pregnancy is one of the causes of a hyperdynamic circulation and the

circulation is already hyperdynamic in cases of aortic regards and that's why patients with more fan syndrome require

repeated echocardiography to follow up with the case let's learn more about morphine

syndrome autosomal dominant inheritance fashion variable expressivity what does that mean some patients have a very mild

form of the disease with few symptoms other patients have moderate symptoms and others have severe symptoms it's

mild versus severe which is similar to the French terms coined by the French physician to Rousseau who said there is

and form plan some patients have the typical classic full-blown picture of the disease with all the symptoms others

have almost no symptoms whereas the defect fbn1 gene on which chromosome chromosome 15 which protein is defective

fibril in one protein this will lead to increased TGF data because it's no longer sequestered and I will no longer

be able to protect elastin so I have an elastin defect contrary to popular belief Marfan syndrome is not a defect

near collagen it's a defect in your elastin big difference a osteogenesis imperfecta is a collagen defect menki's

disease is a collagen defect scurvy is a collagen defect ehlers danlos syndrome is a collagen defect but Marfan is not a

collagen defect it's an elastin defect it's a fibrillen defect it's a connective tissue disorder but it's not

a collagen defect otherwise you'll have to tell me which type of collagen is defective is a type 1 type 2 type 3 Type

4 type 5 Etc and the answer is it's none of these signs and symptoms of Marfan syndrome at chest wall deformities such

as spectacle carinatum and pectus excavatum it could be this or this what does the word carinator means it means

bulging outwards why because a Karina is the Keel of the boat here is the anteroposterior view of the boat

floating on the surface of water and heading towards you this part of the boat that is emerged downstairs is the

Keel of the boat called the Karina so Pectus Karai natum is bulging outwards but pectus excavatum is when my chest

wall is bulging inwards as if it has been evacuated or excavated so it's empty now patients with Marfan syndrome

are very tall and very thin not just the stature is tall their limbs are tall and their span exceeds the height what do I

mean by this here is my head and here are my feet and look at this these are my arms if you measure the distance from

here to here and the distance from here to here in normal people they should be almost the same but in Marfan syndrome

the span is greater than the height and then you can divide the body into two halves upper half and lower half and

what's the center point it will be your umbilicus in normal people the upper half should equal the lower half in

length now Mountain Marfan in Marfan syndrome the lower body segment is usually taller than the upper body

segment next my vertebral column is not straight it is tilted scoliosis they get all kinds of hernias such as inguinal

hernia spider like fingers and toes arachnodeactly dactly means digits arachno means arachnida arachnid like a

spider what are the name of the three meningeal layers that cover the brain and the spinal cord we have the dura

mater the arachnoid matter and Pia Mater what's the external one dura mater ectasia means dilation of the dura mater

this will lead to erosions of the lumbosacral vertebrae not good the skin is hyper elastic I.E not very stable

joints are hyperelastic I.E not very stable why not because I have an elastin defect my connective tissue is not

robust lens subluxation or Worse dislocate location is usually upwards and outwards this can affect my vision

what else can affect your vision retinal detachment and myopia short-sightedness what's the opposite of

myopia hypermetropia Which is far sightedness how do you remember which is which look

at the word Mayo what does Maya mean it means a muscle think of your lens as if it was a muscle Contracting so strongly

that the site or the object falls in front of the retina so you get nearsightedness there is another

mnemonic myopia is a shorter word than hypermetropia therefore myopia is near sightedness but hypermetropia the long

word is a farsightedness now let's talk about vessels and valves what happened to the aortic root it got dilated when

it dilates the cusps get far away from one another they cannot close when they should so I get insufficiency and

regurgitation backflow also so aortic dissection can happen aortic aneurysm can happen why is that cystic medial

necrosis because it's a connective tissue disorder due to an elastin defect because fibrillon 1 is toast and could

not protect and surround the elastin can the aortic regurgitation cause a murmur absolutely what else can lead to a

murmur in these patients mitral valve prolapse why is it prolapsing because the connective tissue support is toast

and when it prolapses it gives me a murmur similar to miter regurgitation however don't forget to add a click

before the murm so you get the murmur of aortic regurgitation and the murmur that's similar to mitral regurgitation

so two regurgitation murmurs don't forget to add the click patients with more fan are tall and thin the typical

candidate for ruptured apical blebs of the lungs leading to Pure spontaneous pneumothorax hyper resonance to chest

percussion however it's unlikely to have a tracheal shift to the opposite side unlike patients with homocystinuria who

had intellectual disability morphine syndrome patients tend to have normal IQ I.E fine intellect normal intellect how

can I diagnose Marfan syndrome history and physical exam echocardiogram for all of these heart problems and of course

genetic testing how can I manage Marfan syndrome manage the patient symptomatically try to correct each one

of these and try to prevent the complications as much as you can some of these features might benefit from

medical management such as beta blockers for all of the heart and vessel symptoms as well as surgical interventions why

for these deformities like scoliosis like hernias Etc and because my valves are toast aortic and mitral I need

prophylaxis for infective endocardial patients with Marfan syndrome require routine repeated

echocardiography to check the status of their heart and vessels especially during pregnancy because during

pregnancy a soft flow systolic murmur develops a hyperdynamic circulation exists because of the increased blood

volume which is caused by increased plasma volume now let me answer the questions of the previous video for you

we had a comparison between folate deficiency and vitamin B12 deficiency which one has anemia both of them what's

going to happen to my Redbox account hemoglobin concentration and hematocrit or packed cell value or volume all three

will decrease in both diseases which type of anemia are we talking both of them have macrocytic megaloblastic

anemia with high MCV in either one reticulocytes are low because without folate or vitamin B12 my bone marrow

cannot replicate its cells due to lack of DNA synthesis if I cannot replicate cells I cannot make red blood cells

anemia I cannot even make reticulocytes which are baby red blood cells so reticulocyte count is lower both of them

can have pancytopenia which means anemia leukopenia and thrombocytopenia not just anemia only vitamin B12 deficiency can

have neurological symptoms for reasons that we discussed in detail in my video on vitamin B12 deficiency and on my

video on homocystinuria speaking of homocysteine it will be elevated in the blood and the urine in either case

however the methylmelon COA or methylmalonic acid is only elevated in vitamin B12 deficiency again please

refer to my video on vitamin B12 deficiency to know why which one is more likely to have a chlorhydria well the

same disease that is usually associated with autoimmune gastritis or pernicious anemia so vitamin B12 which one is more

likely to have gastric adenocarcinoma vitamin B12 because it affects the stomach as you see serum gastrin will be

elevated in some cases of vitamin B12 deficiency why because when my parietal cells are toast they are not making

intrinsic factor they are not making HCL who's gonna get triggered gastrin will go up as a feedback mechanism how can I

manage folate deficiency treat the underlying cause give the patient folate how do I treat vitamin B12 deficiency

treat the underlying cause and give the patient vitamin B12 do you want to learn more about aortic dissection Peripheral

arterial disease acute limb ischemia claudications of the limbs compartment syndrome and the volkman's contractures

then download my surgery high yields corset medicosisperfectsnetis.com to learn

about ards many cardiac arrhythmias angina myocardial infarction ischemic stroke hemorragic stroke and much more

download my emergency medicine high yield scores at meticosisperfectness.com patients with

Marfan syndrome May benefit from beta blockers to learn more about beta blockers calcium channel blockers the

anti-hyperlipidemics antiarythmics anti-anginal antihypertensives diuretics and even

digoxin download my cardiac pharmacology course if you do not want to download my premium courses but would rather watch

them right here on YouTube click the join button choose the highest tier to gain instant access to more than 300

premium videos right now please subscribe hit the Bell smash like support my channel here or here go to my

website to download my courses notes and cases be safe stay happy study hard this is medicosa's perfectionist where

medicine makes perfect sense