Marfan’s syndrome - Connective tissue disorders

Marfan’s syndrome

Definition

Inherited condition resulting in abnormalities of connective tissue causing anomalies in the musculoskeletal, cardiovascular and ocular systems.

Incidence

1 in 15,000.

Aetiology/pathophysiology

Inherited in an autosomal dominant fashion. Mutations occur in the FBN1 gene that codes for the extracellular matrix glycoprotein fibrillin and is on the long arm of chromosome 15. FBN1 mutations also occur in milder phenotypes with features overlapping Marfan’s pheno-type. Twenty-five per cent of cases represent new mutations.

Clinical features

The phenotype is variable and unrelated to the FBN1 mutation.

·        Musculokeletal: Patients have elongated and asymmetrical faces with a high arched palate. There is a reduced upper to lower body segment ratio and an arm span that exceeds the patient’s height. Long thin fingers and toes are termed arachnodactyly. Scoliosis is common along with pectus excavatum (funnel chest).

·        Cardiovascular system: There is degeneration of the media of blood vessel walls:

i.            Dilation of the aortic valve ring producing regurgitation.

ii.            Mitral valve prolapse and associated mitral valve regurgitation.

iii.            Aneurysm formation may occur, usually in the ascending aorta, which may be followed by dissection and/or rupture.

·        Ocular: Weakness of the suspensory ligament of the lens may cause an upward lens dislocation (ectopia lentis).

Investigations

The diagnosis is clinical and can be based on clinical criteria scoring. Once diagnosed patients require periodic aortic imaging to detect early dilation.

Management

β-blockers have been shown to slow aortic dilatation, and lifelong therapy is recommended by the European Society of Cardiology.

At least annual echocardiograms are required with consideration of prophylactic aortic root replacement prior to the development of critical dilatation.

Dislocated lenses are not removed unless conventional visual correcting aids are ineffective.

Orthopaedic intervention may be required.

Genetic counselling should be offered where appropriate.