Marfan syndrome

Overview

Marfan syndrome is a genetic connective tissue disorder that affects the body's skeletal system, cardiovascular system, eyes, and skin. It is characterized by tall stature, long limbs and fingers, flexible joints, and serious complications involving the heart and aorta. The syndrome can range from mild to life-threatening, with symptoms varying greatly among individuals. Marfan syndrome affects approximately 1 in 5,000 people, regardless of gender or ethnicity.

Causes

Marfan syndrome is caused by a mutation in the FBN1 gene, which encodes the protein fibrillin-1, a key component of connective tissue. This mutation leads to weakened connective tissue throughout the body, affecting structural integrity and elasticity. The condition is inherited in an autosomal dominant manner, meaning that only one copy of the defective gene is sufficient to cause the syndrome. However, about 25% of cases result from a spontaneous new mutation with no family history.

Symptoms

The symptoms of Marfan syndrome can vary widely in severity and presentation. Common signs and features include:

• Tall and slender build

• Disproportionately long arms, legs, fingers, and toes (arachnodactyly)

• Flexible joints and flat feet

• Chest deformities (pectus excavatum or pectus carinatum)

• Scoliosis or abnormal curvature of the spine

• Lens dislocation (ectopia lentis) and severe myopia

• Enlarged aorta (aortic root dilation), which may lead to aortic aneurysm or dissection

• Heart valve abnormalities such as mitral valve prolapse

• Stretch marks not related to weight changes

• Fatigue and shortness of breath with exertion

Diagnosis

Diagnosing Marfan syndrome involves a comprehensive evaluation based on clinical features, family history, and genetic testing. Diagnostic steps may include:

• Physical examination: Assessing body proportions, skeletal features, and flexibility.

• Echocardiogram: To check for aortic root dilation and heart valve abnormalities.

• Ophthalmologic exam: To evaluate for lens dislocation and other eye issues.

• Genetic testing: To identify mutations in the FBN1 gene, especially when diagnosis is uncertain.

• Ghent criteria: A set of clinical guidelines used to diagnose Marfan syndrome based on specific systemic features and genetic findings.

Treatment

There is no cure for Marfan syndrome, but with careful management, many complications can be minimized. Treatment strategies include:

• Medications: Beta blockers or angiotensin receptor blockers (ARBs) to reduce stress on the aorta.

• Regular monitoring: Frequent echocardiograms and other imaging studies to monitor aortic size and heart health.

• Surgical intervention: In cases of significant aortic enlargement or valve dysfunction, preventive surgery may be necessary.

• Eye care: Regular eye exams and corrective lenses or surgery for vision problems.

• Orthopedic support: Bracing or surgery for scoliosis or other skeletal issues.

• Activity modifications: Avoidance of high-intensity sports and activities that strain the heart or joints.

• Genetic counseling: For affected individuals and families planning for children.

Prognosis

With early diagnosis and appropriate treatment, individuals with Marfan syndrome can live long and productive lives. Advances in medical monitoring and surgical techniques have significantly improved outcomes and life expectancy. However, lifelong medical care is necessary to manage potential complications, especially those related to the cardiovascular system. Regular follow-ups with a cardiologist and other specialists are essential to ensure ongoing health and safety.