Marfan Syndrome (MFS) is a systemic genetic disorder affecting the body’s connective tissue, which provides the scaffold and support for organs and structures. The condition arises from a defect in a single gene, leading to wide-ranging manifestations. MFS affects various systems, including the heart and blood vessels, the skeleton, and the eyes.
Equal Prevalence and Genetic Cause
Marfan Syndrome affects males and females with equal frequency due to its genetic inheritance pattern. The disorder is classified as autosomal dominant, meaning the gene responsible is located on a non-sex chromosome. Consequently, the inheritance risk is independent of a person’s biological sex.
The underlying cause is a mutation in the FBN1 gene, which resides on chromosome 15. This gene provides instructions for making fibrillin-1, a protein essential for microfibrils, which give connective tissue its strength and elasticity. Since inheritance is dominant, receiving a faulty copy of the gene from just one parent is sufficient to cause the condition.
Approximately 75% of Marfan Syndrome cases are inherited from an affected parent, who has a 50% chance of passing the gene to each child. The remaining cases result from a de novo, or spontaneous, mutation in the FBN1 gene. It is estimated that Marfan Syndrome occurs in about 1 in 5,000 to 10,000 individuals worldwide, with no ethnic or geographical predilection.
Primary Body Systems Affected
The defective fibrillin-1 protein compromises the structural integrity of connective tissue, leading to a spectrum of signs in multiple organ systems. The severity of these manifestations varies significantly among affected individuals. The most serious concerns involve the cardiovascular system, but changes also occur in the skeletal and ocular systems.
Cardiovascular Manifestations
The most life-threatening complication of Marfan Syndrome involves the aorta, the large artery carrying blood away from the heart. Weakened connective tissue in the aortic wall leads to progressive enlargement, known as aortic root dilation or aneurysm. This dilation increases the risk of aortic dissection, a tearing of the inner layer of the aorta.
Regular monitoring is essential because the risk of dissection rises sharply once the aortic root diameter reaches a certain size, typically around 5.0 centimeters in adults. Mitral valve prolapse, where the valve leaflets bulge back into the heart’s upper chamber, is another common finding due to the laxity of the valve tissue.
Skeletal Manifestations
The skeletal system often exhibits distinctive features, characterized by excessive long bone growth. People with MFS are often tall and slender, with disproportionately long limbs and digits, a condition known as arachnodactyly. This overgrowth is related to the disrupted regulation of growth factors by the defective fibrillin-1.
The chest wall commonly displays structural abnormalities, such as pectus excavatum (sunken sternum) or pectus carinatum (protruding sternum). Up to 70% of MFS patients experience these pectus deformities. Spinal curvature, including scoliosis or kyphosis, is also frequently observed and can sometimes be severe enough to affect lung function.
Ocular Manifestations
The primary ocular feature of Marfan Syndrome is ectopia lentis, which occurs in 60% to 80% of affected individuals. This happens because the ciliary zonules, the delicate connective tissue fibers that suspend the lens, are weakened by the fibrillin defect. The lens typically shifts upward and outward, often causing visual impairment.
High-degree myopia, or severe nearsightedness, is also common due to an increased axial length of the eyeball. The combination of ectopia lentis and high myopia predisposes patients to other serious complications, including retinal detachment, which requires prompt surgical intervention to preserve vision.
Identifying Marfan Syndrome
Diagnosis relies on a comprehensive assessment that evaluates the extent of systemic involvement, often guided by the revised Ghent Nosology criteria. This standardized framework assigns a weighted score to various clinical manifestations. The criteria give significant weight to the two “cardinal features”: aortic root dilation and ectopia lentis.
An unequivocal diagnosis can be made in a person without a family history if they have aortic root dilation along with ectopia lentis, or if they have aortic root dilation plus a confirmed FBN1 gene mutation. If these cardinal features are absent, a diagnosis requires a combination of systemic features that meets a minimum systemic score. This complex evaluation ensures accuracy, especially since many features overlap with other connective tissue disorders.
Genetic testing, confirming a pathogenic mutation in the FBN1 gene, plays a prominent role in the diagnostic process. Because the condition affects multiple body systems, diagnosis requires a coordinated effort from a multidisciplinary team of specialists. This team typically includes a cardiologist, an ophthalmologist, a geneticist, and an orthopedist.
Long-Term Monitoring and Treatment
Effective management of Marfan Syndrome is a lifelong endeavor focused on preventing catastrophic cardiovascular complications. Regular monitoring, primarily through echocardiograms, is performed to precisely track the size and growth rate of the aortic root. This non-invasive imaging allows clinicians to determine the optimal timing for prophylactic intervention.
Medical treatment is primarily directed at reducing strain on the aortic wall to slow the rate of dilation. Beta-blockers are commonly prescribed to decrease the heart rate and the force of blood ejection, which lowers the physical stress on the weakened aorta. Angiotensin Receptor Blockers (ARBs), such as losartan, are also used and have been shown to slow aortic enlargement by mitigating the effects of a growth factor pathway implicated in the disease.
When aortic dilation reaches the surgical threshold, generally 5.0 cm, or 4.5 cm in the presence of additional risk factors, prophylactic aortic root repair is recommended. Surgeons replace the damaged section of the aorta with a synthetic graft, often using a valve-sparing technique to preserve the patient’s own aortic valve. This proactive surgical management, combined with medical therapy, has substantially increased the life expectancy for individuals with Marfan Syndrome.