Marfan Syndrome

Marfan 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.