Orthopaedics and Rheumatology: Marfan Syndrome
Marfan Syndrome (sometime Marfan’s Syndrome) is an autosomal dominant connective tissue disorder.
Epidemiology and Aeitiology
- 25% of cases occur without family history
- Reduced life expectancy – average is around 60
Pathology
- 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 – diagnostic is >2 present
o Long limbs, tall, long, spindly fingers (arachnodactyly)
§ The thumb sign – the distal phalanx of the thumb extends beyond the edge of the clenched fist
o Arm length height
o Upwards lens dislocation in the eye (aka ectopia lentis) – the margin of the dislocation lens may been seen through an undilated pupil
o Pectus deformity (e.g. excavatum or carinatum [outwards])
o 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
o Dural ectasia – widening of the neural canal
- Minor signs – may support diagnosis
o Mitral valve prolapse – and accompanying late systolic murmur at the apex
o High arched palate – can cause altered / unusual voice in some patients
o Joint Hypermobility
o Genu recuvatum – hyperextension of the knee, thus is appears to curve backwards
o Scoliosis
o Reduced subcutaneous fat
Diagnosis
- Usually clinical. CT scan may be useful to detect dural ectasia
Treatment
- The disease is incurable.
- Treatment aims to minimise the risk of aortic dissection by preventing excessive dilation of the aortic root. This is usually managed with:
o Β- blockers – e.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
o Annual Echocardiogram – dilation of >5cm is repaired surgically
o Risk in pregnancy – pregnant women are at particularly high risk of cardiac complications.
Homocystinuria
is a disorder that is difficult to distinguish from Marfan Syndrome.
Marfan Syndrome | Homocystinuria |
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 |
Notes by Tom Leach
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