Marfans syndrome

Question 1

Definition

Answer 1

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

Marfans syndrome commonly affects:
– the heart
—- can lead to aortic dissection and aneurysm, also mitral valve prolapse)
– eyes (dislocated lenses, retinal detachment)
– blood vessels
– skeleton (pts are usually tall and thin with unusually long arms, legs, fingers and toes)
—- this is because the long bones grow meaning longer arms and legs

Question 2

Aetiology

Answer 2

Caused by mutations in a gene called FBN1 (fibrillin1)
—- marfans syndrome is autosomal dominant, so even if there’s a normal copy of the gene present with the mutation, it will still cause the disease

Question 3

Pathophysiology

Answer 3

How it should be in a normal person:
– normally the 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 a glycoprotein called fibrillin

—— fibrillin regulates tissue growth, by removing transforming growth factor beta (TGF-beta). TGF- beta stimulates tissue growth.

What happens if someone has marfans syndrome:
– FBN1 gene encode the Fibrillin-1 protein:
—– in marfans syndrome, fibrillin 1 is either dysfunctional or less abundant
—– meaning there are fewer functional microfibrils in the extracellular matrix
—– overall meaning- less tissue elasticity and integrity

– also TGF-beta doesn’t necessarily get removed, meaning that there is more growth of tissues (so people can be taller and have longer limbs, toes and fingers)

Question 4

Clinical presentations

Answer 4

Symptoms are not always present for people

And they can be more or less severe from person to person

Symptoms that are present at birth are known as neonatal marfans syndrome

Heart symptoms:
– aortic dissection and aneurysms (this can become life threatening if it affects the heart)
– the aorta can dilate over time (risk of aortic valve insufficiency)

Eyes:
– lens dislocation
– retinal detachment

Blood vessels:
– can cause inflammation of blood vessels

Skeleton:
– Tall and thin with unusually long arms, legs, toes and fingers
—- called (marfanoid body habitus)
—- Long fingers and toes called- (Arachnodactyly)

– pectus carinatum and pectus excavatum
– flexible joints may be seen
– scoliosis
– inability to extend the elbows to 180 degrees
– downward slant to the eyes

Lung presentation:
– spontaneous pneumothorax
– apical blebs

Mouth:
– high arched palate

Question 5

Investigations

Answer 5

Heart tests:
– ECG
– CT scan
– MRI scan

Eye tests:
– slit-lamp test- checks for lens dislocation, cataracts or a detached retina

Genetic testing:
– often used to confirm marfans 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 dislocated lens:
– can be replaced with an artificial one

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