Marfan syndrome

Question 1

Definition

Answer 1

An inherited disorder that affects the connective tissue- the fibres that support and anchor your organs and other structures in your body.

Marfan syndrome most commonly affects:
– the heart
– eyes
– blood vessels
– skeleton

Can be mild or severe

If the aorta is affected it can become life threatening

Question 2

Aetiology

Answer 2

Caused by mutations in a gene called FBN1 (Fibrillin 1)
– marfans syndrome is also autosomal so even if there is a normal gene there with the mutated gene, the condition will still occur

Question 3

Pathophysiology

Answer 3

How things should be normally:
– normally interstitial space of various body tissues is full of microfibrils- which are strong rope like structures that provide tissue integrity and form connective tissue.
– main component of microfibrils is fibrillin (regulates tissue growth by removing (sequestering) TGF-beta, as TGF-beta stimulates tissue growth

What happens during Marfan syndrome:
– FBN1 gene encodes the fibrillin-1 protein:
—- in marfans syndrome, fibrillin 1 is either dysfunctional or less abundant
—- meaning there are fewer functional microfibrils in there extracellular matrix
overall meaning- LESS ELASTICITY AND INTEGRITY

—- also, TGF beta doesn’t get sequestered as well, meaning there could be more growth of the connective tissues. As there is connective tissue surrounding every major organ it can occur anywhere in the body

Question 4

Clinical presentation

Answer 4

Symptoms are not always present and not at birth either
neonatal marfan syndrome- symptoms present at birth
can depend on severity from person to person

Skeletal symptoms:
– tall and thin with unusually long arms, legs, toes and fingers
—- due to TGF-beta not being sequestered the bones grow quicker and more

– chest can point outwards (pectus carinatum) or cave inwards (pectus excavated)

– flexibile joints may be seen
– scoliosis
– downward slant to the eyes

Skin presentations:
– stretch marks

Lung presentations:
– cause bulla to form, which could eventually lead to a pneumothorax

Eyes presentation:
– detached retina or lens dislocation

Cardiovascular presentation:
– aorta dilates over time
—- risk of aortic valve insufficiency

– aorta can undergo cystic medial necrosis
Both of these things weaken the aorta meaning its more susceptible to:
– aneurysm
– dissection
– rupture

– mitral valve prolapse

Question 5

Investigations

Answer 5

Heart tests:
– ECG
– CT
– MRI
– if diagnosed with Marfan syndrome, regular imaging tests will be needed to monitor the size and condition of the aorta.

Eye tests:
– Slit-lamp exam- tests for lens dislocation, cataracts or a detached retina
– eye pressure test- checks for glaucoma

Genetic testing:
– often used to confirm Marfan syndrome
– if mutation is found, family members will also need to be tested

Question 6

Treatment

Answer 6

No cure but there are treatments for some of the symptoms

For a dislocated lens:
– surgical repair with an artificial one

for a widened aorta:
– can be surgically repaired
– beta blockers may help
– angiotensin receptor blocker- losartan (decreases TGF-beta signalling)