Marfan Syndrome
Print Friendly, PDF & Email

almostadoctor app banner for android and iOS almostadoctor iPhone, iPad and android apps almostadoctor iOS app almostadoctor android app


Marfan Syndrome (sometime Marfan’s Syndrome, MFS) is a genetic (autosomal dominant) connective tissue disorder. Marfan syndrome is the most common connective tissue disorder. It is associated with characteristic malformation of the skin, bones, heart, eyes and dura mater. However, most cases are mild and patients typically have a near normal life expectancy.
Marfan syndrome is caused by defects in the gene that encodes for fibrillin 1 – an elastin matrix glycoprotein – located on chromosome 15q21. The defects are inherited in an autosomal dominant fashion with complete penetrance, however the phenotype can vary – leading to varying symptoms within the same family. There are over 1,000 known different mutations – it is thought that each individual family probably has its own unique mutation.
Marfan syndrome untreated can lead to significant aortic root dilatation and risk of dissection. 1 in 10 patients with Marfan’s die from this complication. However, modern treatments mean that the life expectancy for patients with Marfan’s is now near-normal.
Diagnosis is performed using the Ghent diagnostic criteria – particularly in regards to family history, presence of ectopic lentils, and dilated aortic root.
The mainstay of treatment is the use of beta-blockers to reduce arterial pressure and these are proven to reduce the development of a dilated aortic root and aortic aneurysm. Aortic / cardiac surgery may also be considered.

Epidemiology and Aeitiology

  • 20-30 cases per 100 000
    • Similar all around the world – there doesn’t appear to regional variation
  • 25% of cases occur without family history – most commonly due to advanced paternal age
  • Reduced life expectancy – modern treatments usually mean that this is now almost-normal life expectancy. Without treatment in the past the average life expectancy was 32


  • The result of a mutation in the fibrillin-1 gene (FBN-1) which results in decreased production of extracellular microfibril. Microfibril is involved in the maintenance of elastic fibres, and as a result, there is an alteration in the properties of elastic fibres

Signs and Symptoms

These can be divided into major and minor signs:

Major signs – used in the Ghent diagnostic criteria

  •  Long limbs, tall, long, spindly fingers (arachnodactyly)
    • The thumb sign – the distal phalanx of the thumb extends beyond the edge of the clenched fist
  • Arm length height
  • Upwards lens dislocation in the eye (aka ectopia lentis) – the margin of the dislocation lens may been seen through an undilated pupil
  • Pectus deformity (e.g. excavatum or carinatum [outwards])
  • Aortic dissection / dilatiation – particularly at the aortic root. The arotic media is less resistant to stretching, particularly in areas of high pressure – hence the involvement of the aortic root. In severe cases, dissection can occur before the age of 10! Aortic regurg and endocarditis are also common
  • Dural ectasia – widening of the neural canal

Minor signs – may support diagnosis

  • Mitral valve prolapse – and accompanying late systolic murmur at the apex
  • High arched palate – can cause altered / unusual voice in some patients
  • Joint Hypermobility
  • Genu recuvatum – hyperextension of the knee, thus is appears to curve backwards
  • Scoliosis
  • Reduced subcutaneous fat
Hypermobility in Marfan Syndrome
Hypermobility in Marfan Syndrome
Skin laxity in Marfan Syndrome
Skin laxity in Marfan Syndrome


  • Diagnosis is done using the Ghent criteria (most recently revised in 2010).
  • CT scan may be useful to detect dural ectasia
  • Echocardiogram can be used to estimate the aortic root diameter
  • Genetic testing was previously not commonly performed, due to the wide variation in the number of possible defects, and the fact that many people with fibrillin-1 defects do not have Marfan syndrome – it was often not very useful. However more recently as techniques it improve it can help to rapidly confirm a diagnosis, or be used in suspected cases in children who do not (yet) meet the diagnostic criteria

Once diagnosis has been made, patients should have:

  • CT of the entire aorta to look for areas aneurysm
  • Annual echocardiogram to check aortic root size and valve function
  • Holter monitor – to asses for arrhythmia
  • MRI to assess for dural ectasia
  • Pelvic x-ray – may show protrusion of the acetabulum into the pelvis – present in 50% of cases

Differential diagnosis


The disease is incurable. Management aims to reduce progression of the consequence of Marfan syndrome. Patients should be managed by a multidisciplinary team than includes a cardiologist, ophthalmologist, geneticist and orthopaedic surgeon.

No medical treatments include:

  • Psychological assessment (if indicated). Many patients have reduced self esteem due to concerns about their appearance
  • Avoidance of high intensity physical exercise – as this can accelerate the progression of aortic root dilatation and dissection. Contact sports and other sports that increase intra-thoracic pressure – such as scuba diving, weight lifting, climbing steep inclines and gymnastics should also be avoided

 Medical aims to minimise the risk of aortic dissection by preventing excessive dilation of the aortic root. This is usually managed with:

  • Β- blockerse.g. atenolol, propanolol – these reduce the contractility of the heart, and thus reduce the pressure in the aortic root, reducing the risk of dilation and dissection. They are often started at a young age (i.e. paediatrics)
  • Angiotensin II receptor blockers (especially losartan) may also be considered as an alternative. Early studies have been promising but some larger trials showed no benefit over atenolol

Some patients may consider prophylactic aortic root surgery. This is proven to prevent dissection. This is performed using a Dracon(R) device and is called the David procedure. 

  • Annual Echocardiogramdilation of >5cm is repaired surgically
  • Risk in pregnancypregnant women are at particularly high risk of cardiac complications.


  • Aortic root dilation and dissection
  • Occular:
  • Orthopaedic
    • Scoliosis
    • Other bone deformities

Due to increasing life expectancies (thanks to propranolol) these complications now affect more patients

In pregnancy

Pregnancy requires specialist support

  • Increased risk of aortic complications in pregnancy
  • 50% chance of an affected baby – patients should be referred for genetic counselling
  • Patients with an aortic root of >45mm should be strongly discouraged from pregnancy without a prior repair


is a disorder that is difficult to distinguish from Marfan Syndrome.
Marfan Syndrome
No urinary markers
Homocystine in urine
Heart signs
Heart not usually affected
Upwards lens dislocation
Downwards lens dislocation
Intelligence not affected
Reduced mental ability
Non-reversable changes
Responds to pyridoxine


  • Marfan syndrome –
  • Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

Read more about our sources

Related Articles

Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

This Post Has One Comment

Leave a Reply