Medical Genetics

Marfan syndrome

An autosomal-dominant FBN1-related connective-tissue disorder affecting the aorta, eyes and skeleton; tall stature and ectopia lentis are recognisable clues, but progressive aortic-root disease and dissection are the life-threatening priorities.

In a nutshell

Marfan syndrome is an autosomal-dominant FBN1-related connective-tissue disorder. The key danger is silent aortic-root dilatation progressing to dissection; ectopia lentis and a systemic skeletal pattern support the revised Ghent diagnosis. Baseline echocardiography, ophthalmology and aortic CT or MRI are followed by specialist surveillance. Beta-blockers or ARBs may reduce aortic dilatation, activity should avoid contact and strenuous isometric stress, and aortic surgery is an experienced-team decision based on diameter, growth and risk factors. Pregnancy needs preconception maternal-cardiac planning.

Classic presentation

A tall person with long fingers, pectus or scoliosis and upward lens displacement is found to have a dilated aortic root on echocardiography. Confirm the phenotype against the revised Ghent criteria and refer to inherited-aortopathy services.

Key points

FBN1-related connective-tissue disease is autosomal dominant; a child of an affected parent has a 50% chance of inheriting the variant.
Cardiovascular severity can be disproportionate to skeletal or ocular features; aortic disease may be silent.
Use the revised Ghent criteria; tall stature, joint laxity or a positive wrist sign alone is not diagnostic.
Baseline assessment includes echocardiography, ophthalmology and CT or MRI of the aorta, followed by regular surveillance.
Consider beta-blocker or ARB therapy through the specialist team and follow the BNF; review medication before pregnancy.
Aortic-root surgery is individualised by an experienced aortic team using diameter, growth, body-size context, family history, regurgitation and pregnancy plans.
Sudden severe chest or back pain, collapse or neurological symptoms is an aortic emergency.

First-line investigation

Expert clinical and family-history assessment, echocardiography of the aortic root, ophthalmic examination for ectopia lentis, and clinical-genetics or aortopathy review with FBN1 testing where indicated.

Management

Recognise aortic and visual emergencies

Sudden severe chest, back or abdominal pain, collapse, pulse or blood-pressure difference or new neurological symptoms needs emergency aortic imaging and cardiothoracic or vascular assessment.^3,1
Sudden visual loss, flashes or floaters, painful red eye or acute visual change needs urgent ophthalmology assessment.^6,4

Confirm and establish baseline risk

Use the revised Ghent framework with family history, systemic examination, echocardiography, ophthalmology and expert genetics or aortopathy review; arrange baseline CT or MRI of the aorta in confirmed disease.^4,1
Consider beta-blocker or ARB therapy through the specialist team and discuss safer physical activity, avoiding contact and strenuous isometric exercise.^1,7

Surveil and refer for aortic intervention

Repeat aortic imaging at an interval determined by root size and growth, usually yearly when stable, and refer early to an experienced aortic team as the surgical threshold or high-risk features are approached.^1,3
Individualise surgery using maximum and indexed diameter, growth, family history, regurgitation, valve-sparing options and pregnancy plans; do not wait for symptoms.^3,1

Protect eyes, family and pregnancy

Maintain ophthalmology, skeletal and pulmonary care and arrange clinical-genetics counselling with cascade testing or reproductive options when appropriate.^4,1
Offer preconception maternal-cardiac counselling, review the aorta and medications, and continue close specialist imaging during pregnancy and postpartum.^5,1

Exam traps

Lens dislocation in Marfan syndrome is classically upward or superotemporal; downward displacement suggests homocystinuria.
A normal-looking skeleton does not exclude dangerous aortic disease, and a striking marfanoid habitus does not establish the diagnosis.
MRI or echocardiography supports surveillance; the surgical decision is not based on symptoms alone or on a single unindexed measurement.
NICE HTG623 notes that some clinicians recommend pre-emptive surgery at 45 mm or more; the current threshold is an aortic-team decision with risk factors and centre expertise.
Avoid contact sports and strenuous isometric exercise, but do not advise complete inactivity.
Review ACE inhibitors and ARBs before pregnancy because medication and monitoring need specialist adjustment.

Illustrations

Positive wrist sign in Marfan syndromeA clinical photograph demonstrating the positive Walker-Murdoch wrist sign, used as one systemic skeletal feature and not as a standalone diagnosis.Seans22, Wikimedia Commons · CC0

Ectopia lentis in Marfan syndromeA slit-lamp image showing lens displacement, a specific ocular feature that must be interpreted within the revised Ghent diagnostic framework.Imrankabirhossain, Wikimedia Commons · CC-BY-SA-4.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.