Marfan Syndrome

What causes Marfan syndrome

The FBN1 gene makes fibrillin-1, a protein that forms elastic fibers in connective tissue and regulates a growth signal called TGF-beta. Faulty fibrillin weakens tissues, especially in the aorta, eye lens ligaments and skeleton.

Marfan syndrome is autosomal dominant: one altered copy causes it, and each child of an affected parent has a 50% chance of inheriting it. About 25% of people have a new mutation with no family history.

Signs and symptoms

Heart and blood vessels

• aortic root dilation: gradual widening of the aorta where it leaves the heart, usually silent
• aortic dissection: a tear in the aortic wall, a life-threatening emergency
• mitral valve prolapse and leaking heart valves
• irregular heart rhythms

Eyes

• ectopia lentis: lens dislocation in about 60%, causing blurred vision
• severe nearsightedness
• higher risk of retinal detachment, early cataracts and glaucoma

Skeleton

• tall stature with long arms, legs and fingers (arachnodactyly)
• arm span greater than height
• chest that sinks in (pectus excavatum) or sticks out (pectus carinatum)
• scoliosis
• flexible joints, flat feet
• high, arched palate with crowded teeth
• positive "thumb sign" and "wrist sign"

Other

• stretch marks without weight change
• spontaneous collapsed lung
• dural ectasia (widening of the spinal sac), causing back pain or headaches
• sleep apnea

Diagnosis

Diagnosis uses the revised Ghent criteria, which combine:

• aortic root enlargement measured by echocardiogram (adjusted for body size)
• lens dislocation
• an FBN1 gene variant
• a family history of Marfan syndrome
• a "systemic score" of skeletal and other features

Tests include echocardiogram, eye exam with slit lamp, and genetic testing. Imaging of the entire aorta (CT or MRI) is done periodically. Similar conditions, such as Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome, must be considered.

Treatment

Heart and aorta

• beta-blockers and/or angiotensin receptor blockers (losartan, irbesartan) to slow aortic enlargement
• echocardiogram at least yearly, more often if the aorta is growing
• preventive aortic root surgery (valve-sparing root replacement or composite graft) when the aortic root reaches about 5.0 cm, or earlier with rapid growth, a family history of dissection, or planned pregnancy
• blood pressure control
• avoid fluoroquinolone antibiotics where possible, as they are associated with aortic risk

Eyes

Yearly eye exams; glasses or contact lenses; lens surgery if needed; prompt treatment of retinal tears.

Skeleton

Bracing or surgery for scoliosis; chest wall surgery in selected cases; orthopedic and physical therapy support.

Lifestyle

• moderate aerobic activity is encouraged
• avoid contact sports, competitive or high-intensity exertion, heavy weightlifting and isometric exercise
• avoid stimulants and decongestants that raise blood pressure

Pregnancy

Pregnancy increases the risk of aortic dissection. Women with Marfan syndrome should have pre-pregnancy counseling and be managed by a high-risk pregnancy team with cardiology input.

Outlook

Before modern treatment, average life expectancy was around 40 years. With monitoring, medicines and preventive surgery, people with Marfan syndrome now often live into their 70s and beyond.

Frequently asked questions

What are the signs of Marfan syndrome?

Common signs are tall, thin build with long arms, legs and fingers, a sunken or protruding chest, scoliosis, flexible joints, nearsightedness or a dislocated lens, and stretch marks. The most important sign, aortic enlargement, is usually silent and found on an echocardiogram.

What is the life expectancy of someone with Marfan syndrome?

With modern care, including regular aortic imaging, medicines and preventive surgery, people with Marfan syndrome can expect a near-normal lifespan, often into their 70s or beyond.

Is Marfan syndrome inherited?

Yes. It is autosomal dominant, so a parent with Marfan syndrome has a 50% chance of passing it to each child. About a quarter of cases are caused by a new gene change in someone without a family history.

Can people with Marfan syndrome exercise?

Yes. Moderate, low-intensity aerobic exercise such as walking, cycling or swimming at a comfortable pace is encouraged. Contact sports, competitive sports and heavy lifting should generally be avoided to protect the aorta and eyes.