Marfan syndrome is an autosomal dominant genetic disease affecting connective tissue. It is thought to affect 1 in 5000 people.
Diagnosis can be difficult because it can manifest differently in each individual, even amongst members of the same family (different expression).
Some features will also be present in people without the syndrome. Diagnosis is clinical, based on a combination of characteristic clinical signs (Ghent criteria).
Most cases need a combined clinical and radiological assessment. Therefore, referral to the Regional Genetics Centre is advisable with regards to making the diagnosis and coordinating the other specialities which may need to be involved.
Spontaneous mutations occur, but 3 out of 4 people with Marfan syndrome will have inherited it from one of their parents, although the diagnosis may not have been made previously in the parent if they are mildly affected.
Symptoms can vary widely in severity, the vast majority present with mild manifestations, but 1 in 10 will be more severely affected.
Features
Skeletal
Limbs disproportionately long for trunk, long thin fingers and toes (arachnodactly), malocclusive teeth and high arched narrow palate, joint laxity, scoliosis, pectus excavatum & carinatum (pigeon chest), pes planus
Cardiac
Aortic dilatation, aortic dissection, mitral valve prolapse.
Eyes
Lens dislocation, myopia, cataracts, retinal detachment and increased risk of early onset glaucoma.
Pulmonary
Spontaneous pneumothorax, sleep apnoea, increased risk of Chronic Obstructive Pulmonary Disease (COPD).
Nervous system
Dural ectasia of spinal cord leading to symptoms of low back, abdominal and leg pain or paresthesiae and headache.
Skin
Stretch marks and herniae.
Genetics
Marfan syndrome is caused by mutations in the gene on chromosome 15 (FBN1) which determines the structure of the connective tissue protein called fibrillin. Over 200 mutations are known.
Genetic testing is available, but has many limitations. It is time consuming and expensive, but also between 10-30% of people with Marfan syndrome DO NOT have an identifiable mutation in the fibrillin gene. Also mutations within the gene are found in other syndromes which overlap clinically with Marfan syndrome.
Clinical diagnosis remains the way forward
Genetic testing may be available as an option for prenatal diagnosis, since children of an affected individual have a 50% chance of inheriting the gene, although it is not possible to predict how severely the child would be affected. Diagnosis in young children can be difficult, as many of the features do not become apparent until late teenage/early adulthood, and often children at risk will simply need to be monitored until they reach adolescence.
Management
Management will depend on which problems are present, but regular review by a number of specialities may be required. Regular cardiac review may be needed, and this is especially important for women during pregnancy because of the extra stresses put upon the cardiovascular system. Some people with Marfan syndrome will be prescribed beta blockers or angiotensin II antagonists to reduce the risk of aortic problems.
General lifestyle advice should be to avoid smoking, especially as they can be at increased risk of COPD. Also certain contact sports and activities such as scuba diving may need to be avoided.
