Case Study 5

Question 1

A 19 year old student is referred to your clinic because of tall stature and joint hyper mobility. She was recently in hospital with a pneumothorax.
Other clinical features/history:
- she is myopic
- she has stretch marks on the skin over the lumbar spine
- systolic murmur
- father is also tall
- paternal uncle died suddenly at age of 43 from what was said to be a heart attack
- ECG carried out on admission for pneumothorax was normal
What diagnosis do you expect?

Answer 1

Marfan Syndrome

Question 2

Give two further imaging investigations that you would consider

Answer 2

• CXR
• Echocardiogram
• Pelvic X-ray
• MRI scan of lumbar spine

Question 3

Give a reason for performing a CXR

Answer 3

CXR might show apical blebs, a sign of Marfan syndrome

Question 4

Give a reason for performing an echocardiogram

Answer 4

Mandatory

• to assess aortic root diameter at the sinus of Valsalva
• confirm reason for murmur

Question 5

Give a reason for performing a pelvic x-ray

Answer 5

May show protrusio acetabulae, a feature of Marfan syndrome

Question 6

Give a reason for performing an MRI scan

Answer 6

May show dural ectasia, a major feature of Marfan syndrome in the Ghent clinical diagnostic criteria

Question 7

An echocardiogram shows mitral valve prolapse with no significant regurgitation.
What four further points of information would you seek from the family history or medical records?

Answer 7

• is the patient’s father tall, does he have myopia or other visual difficulties, hypermobility or any cardiac disorder
• cause of death for paternal uncle
• did the uncle have myopia/other visual difficulties/hypermobility/cardiac disorder
• what happened to her paternal grandparents - did either of them have any features suspicious of Marfan syndrome

Question 8

Your diagnosis is confirmed but the patient does not fulfil the accepted clinical diagnostic criteria. What two further investigations of the patient or her family would you do next to try to clarify the situation?

Answer 8

• investigate her father including imaging studies

- take a blood sample for fibrillin mutation testing

Question 9

Give four reasons why these further investigations may or may not provide a diagnosis

Answer 9

• some features display age-dependant penetrance so her father may fulfil the criteria even if she doesn’t
• under Ghent criteria, an independently affected first degree relative counts as a major feature and therefore might make diagnosis for the patient
• Some fibrillin mutations are known to cause Marfan syndrome so if present would support the diagnosis
• other fibrillin mutations are of unknown consequence or have been found in people with Marfan-like conditions
• mutations in other genes may occasionally cause Marfan syndrome so some fibrillin mutations will not confirm the diagnosis

Question 10

Give the main treatments used to prevent aortic dissection which may be associated with her diagnosis

Answer 10

• antihypertensives
• prophylactic aortic root surgery
• lifestyle advice