Marfan syndrome

Marfan syndrome is a multi-system connective tissue condition that primarily alters the skeleton, heart, blood vessels, and eyes. It is caused by pathogenic variants in the FBN1 gene, which encodes fibrillin-1, a protein that helps form the body’s elastic fibers and regulates TGF-beta signaling. The disorder can be diagnosed at any age, but features often become more apparent in childhood or adolescence when rapid growth accentuates skeletal findings. It affects approximately 1 to 5 in every 10,000 people, making it relatively common among uncommon conditions. Severity and symptoms vary widely between individuals, even within the same family.

Clinicians recognize several hallmark findings, including tall stature with disproportionately long limbs, arachnodactyly, aortic root dilation that can lead to life-threatening dissection, ectopia lentis, and distinct chest wall shapes such as pectus excavatum or carinatum. Musculoskeletal features dominate early childhood and the teen years. Rapid growth may uncover scoliosis, chest wall asymmetry, flat or highly arched feet, and joint laxity that causes easy fatigue or pain. Over time, the spine can curve forward (thoracic lordosis) and the dura—the protective covering around the spinal cord—may widen (dural ectasia), sometimes causing back pain or headaches. Cardiovascular involvement centers on progressive enlargement of the aortic root and valves. Mitral or tricuspid valve prolapse with murmur or regurgitation can produce palpitations, shortness of breath, or arrhythmia. Ocular findings often appear in childhood. Many individuals develop severe nearsightedness, and about half experience lens dislocation, which may blur vision or predispose to early cataract. Not all individuals experience all features, and severity varies considerably. Some people live for years with only mild skeletal differences, while others face early cardiac or ocular complications that require prompt intervention.

Marfan syndrome results from alterations in the FBN1 gene on chromosome 15. Fibrillin-1 is a structural component of extracellular microfibrils that gives tissues resilience and also modulates TGF-beta activity. Disruption of fibrillin-1 weakens connective tissue and alters cell signaling, which together lead to the diverse findings seen in this condition. The disorder is inherited in an autosomal dominant pattern, meaning a person needs only one altered copy of FBN1 to be affected and each child of an affected individual has a 50 percent chance of inheriting the variant. Approximately 25 percent of cases arise from a new (de novo) variant that is not present in either parent, so a family history may be absent. When a variant is de novo, recurrence risk for siblings is low, although the affected individual can pass the variant to future children. Even within the same family, the type and severity of symptoms can vary considerably, a phenomenon known as variable expressivity. Genetic counseling is recommended for anyone with a diagnosis or family history of Marfan syndrome.

Management focuses on protecting the aorta and addressing complications through coordinated multidisciplinary care. Beta-blockers such as atenolol or propranolol are commonly prescribed to reduce aortic wall stress, and the angiotensin-receptor blocker losartan may be added or substituted for added aortic protection. Regular surveillance is critical: most individuals undergo echocardiographic monitoring of aortic root diameter at least yearly, and ophthalmologic examinations track lens position and vision. Activity modification that avoids contact sports or intense isometric exercise further lowers the risk of aortic injury. When the aortic root approaches a surgical threshold, prophylactic aortic root replacement by an experienced cardiothoracic surgeon can prevent dissection and dramatically improve survival. Orthopedic interventions address severe scoliosis or chest wall deformities, and glasses or lens surgery restore vision when ectopia lentis or cataract interferes with daily life. Currently, no therapies are specifically approved by regulatory agencies for Marfan syndrome, so treatment remains individualized and symptom-directed. Genetic counseling, psychosocial support, and connection with specialist teams help families navigate lifelong monitoring and decision-making.

With modern medical therapy, regular monitoring, and timely aortic surgery, many individuals with Marfan syndrome enjoy a near-normal life expectancy and can pursue education, careers, and family life. Nonetheless, outcomes depend on early detection of aortic enlargement, adherence to treatment and surveillance plans, and management of ocular or skeletal complications. The course is highly variable, and some people encounter significant challenges in adolescence or early adulthood, while others remain relatively unaffected for decades. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors who can coordinate specialty care and keep them informed about emerging options.

Marfan syndrome is an active research area with numerous ongoing clinical trials exploring medications that further modulate TGF-beta signaling, refinements in aortic root surgery, and early-stage gene therapy strategies aimed at correcting or silencing pathogenic FBN1 variants. Individuals interested in clinical trials can search ClinicalTrials.gov or discuss opportunities with their care team to determine eligibility.