OVERVIEW

What is Marfan Syndrome?

Marfan syndrome is an autosomal dominant genetic disorder primarily affecting fibrous connective tissue (which is distributed throughout the body).

The clinical severity of this disease and related conditions varies widely, ranging from mild cases with isolated features of Marfan syndrome to severe, rapidly progressive multi-organ system involvement in newborns. Currently, it is widely believed that the disorder mainly affects three organ systems: skeletal, ocular, and cardiovascular.

The condition was first reported in 1896 by French pediatrician Antoine Marfan, after whom it is named. Although many clinicians evaluate the disease based on typical ocular, cardiovascular, and musculoskeletal abnormalities, patients may also exhibit involvement of the lungs, skin, and central nervous system.

Life-threatening cardiovascular complications often require medical or surgical intervention. Most affected individuals with cardiovascular involvement die in early or middle adulthood.

What is Connective Tissue?

All human organs contain connective tissue, particularly bones, ligaments, eyes, cardiovascular system, lungs, and nervous system. Connective tissue plays vital roles in various stages of life, such as prenatal development, postnatal growth, joint cushioning, and light transmission in the eyes.

Is Marfan Syndrome Common?

Reported prevalence of Marfan syndrome is approximately 1 in 3,000 to 1 in 5,000 individuals.

SYMPTOMS

What are the main manifestations of Marfan syndrome?

The typical manifestations of this disease include skeletal system symptoms, cardiovascular symptoms, and ocular lesions:

Ocular symptoms:

• Lens dislocation: A classic ocular manifestation, occurring in 60%–70% of patients (some reports suggest 100%). Most cases occur between 2 months and 6 years of age, with an average onset at 2.7 years, though some reports indicate a peak incidence between 10–19 years.
• Refractive errors: Progressive myopia and difficult-to-correct astigmatism are among the most common ocular manifestations. Myopia often becomes highly prevalent after age 6.
• Retinal detachment: The most severe ocular complication, affecting 10%–25% of Marfan syndrome patients, with one-third experiencing bilateral detachment.
• Others: Patients may also develop glaucoma, strabismus, or amblyopia.

Skeletal system manifestations:

• Arachnodactyly (long fingers and toes): A hallmark feature.
• Arm span typically exceeds height, and average height is above the population norm.
• Dolichocephaly (long, narrow skull), frontal bossing, retrognathia or prognathism, underdeveloped cheekbones, and a "downturned" facial expression.
• High-arched palate leading to dental crowding.
• Sternal and vertebral deformities, resulting in scoliosis or kyphoscoliosis.
• Joint hypermobility, contractures, or dislocations.

Cardiovascular manifestations:

• Aortic dilation: Present in ~50% of pediatric patients and 70%–80% of adults.
• Aortic aneurysms: May rupture suddenly, causing life-threatening emergencies. Patients often experience acute, tearing chest pain.
• Mitral valve prolapse (MVP): Often the earliest cardiovascular sign. Echocardiography reveals MVP (posterior leaflet) in 80% of patients, regardless of age or sex.
• Aortic valve regurgitation: Progressive and common, affecting 70% of adult patients.

Other systemic manifestations:

• Skin: Striae atrophicae (stretch marks) in ~2/3 of patients, caused by elastic fiber fragmentation.
• Inguinal hernias: Frequently observed.
• Respiratory: Spontaneous pneumothorax, often recurrent due to apical bleb rupture.
• Renal: Polycystic kidney disease may occur.
• Neurological: Dural ectasia.

Do all Marfan syndrome patients have identical symptoms?

No, clinical manifestations vary among patients.

This is because over 1,750 FBN1 gene mutations have been identified, all capable of causing Marfan syndrome. Mutations are randomly distributed across the gene, leading to highly variable phenotypes—even within the same family.

Why is Marfan syndrome called "spider disease"?

The condition is nicknamed "spider disease" (or arachnodactyly syndrome) due to the characteristic elongated fingers and toes resembling spider legs.

Why is Marfan syndrome called the "genius disease"?

Patients often exhibit exceptional height (1.8–2.1 meters), perceived as a "gift" conferring advantages in fields like athletics—hence the "genius" moniker.

What is the most severe complication of Marfan syndrome?

The greatest risk is aortic aneurysm/dissection rupture, causing sudden death. Mitral valve regurgitation may also lead to fatal heart failure. Cardiac involvement requires prompt intervention (e.g., surgery) to improve long-term survival.

CAUSES

What causes Marfan syndrome?

The pathogenic gene of Marfan syndrome was identified in 1991 as the FBN1 gene located on human chromosome 15. This gene encodes fibrillin-1, and mutations in it can alter certain amino acids in fibrillin, interfering with or causing errors in microfibril assembly. This disrupts the structure of fibrillin, reduces its synthesis quality and quantity, and impairs its biological function.

Marfan syndrome is an autosomal dominant genetic disorder. Can affected individuals have healthy children?

Normal individuals have two normal alleles. For patients with autosomal dominant genetic disorders, the presence of just one pathogenic gene out of the two is sufficient to cause the disease.

Therefore, according to genetic principles, if a Marfan syndrome patient partners with a healthy individual, their children have a 50% chance of inheriting the disease. If two Marfan syndrome patients partner, their children have a 3/4 chance of being affected.

It is worth noting that if a Marfan syndrome patient carries two pathogenic genes, all of their children will inherit the disease.

If the unaffected children of a Marfan syndrome patient marry a normal person, can they still have affected offspring?

If unaffected children marry a normal person, their descendants generally will not have the disease.

Why can parents who are normal give birth to a child with Marfan syndrome?

Not every Marfan syndrome patient has a family history. Reports indicate that about 1/4 of patients have no identifiable family history, which may be due to acquired chromosomal mutations.

Are there more male or female patients with Marfan syndrome?

The disease is unrelated to gender, with equal probability of occurrence in males and females.

DIAGNOSIS

How is Marfan syndrome diagnosed?

The diagnosis of Marfan syndrome was previously based primarily on its clinical manifestations.

The "Berlin Diagnostic Criteria," adopted in 1986, established a unified standard for diagnosing the disease. These criteria emphasized the involvement of major organ systems (skeletal, cardiovascular, ocular, and central nervous systems, with aortic root dilation being particularly significant), other systemic manifestations, and family history as key diagnostic factors. However, the misdiagnosis rate remained high.

In 1996, the "Ghent Diagnostic Criteria (1996)" were introduced and later revised in 2010 as the "Ghent Diagnostic Criteria (2010)." These criteria are more practical, represent an improvement over previous standards, and offer certain advantages. However, the "Ghent Criteria (2010)" still face some controversy and require further refinement in the future.

With advancements in molecular diagnostic techniques, genetic testing has gradually become a crucial tool in diagnosing Marfan syndrome, serving as an essential diagnostic method. Therefore, every suspected case of Marfan syndrome should undergo genetic testing to assist clinicians in confirming the diagnosis.

What tests are needed for suspected Marfan syndrome?

The following tests may help doctors diagnose and differentiate the condition: electrocardiogram (ECG), echocardiogram, chest X-ray, ophthalmologic examinations, cardiac CT/MRI, and cardiovascular angiography. Of course, the most powerful diagnostic tool is genetic testing.

TREATMENT

Which department should Marfan syndrome patients visit?

Depending on the affected tissues and organs, patients may need to consult different departments.

For primarily ocular manifestations, an ophthalmology consultation is recommended; for cardiovascular involvement, cardiology and cardiothoracic surgery should be sought.

How should Marfan syndrome be treated?

Treatment for Marfan syndrome can be divided into two main categories: medication and surgery:

• Medication:

  • Beta-blockers: Adults with MFS and aortic aneurysms should be treated with beta-blockers to slow aortic dilation, unless contraindicated. For pregnant women, labetalol or metoprolol is preferred.

  • Angiotensin II receptor blockers (ARBs): An ARB (e.g., losartan) may be added to beta-blocker therapy based on patient tolerance to further reduce aortic root dilation in MFS patients.

  • Angiotensin-converting enzyme inhibitors (ACEIs): For patients with thoracic aortic aneurysms (regardless of etiology), it is reasonable to use beta-blockers and ARBs or ACEIs to lower blood pressure to the minimum tolerated level without adverse effects.

  • The role of other medications in MFS remains unclear.

• Surgery: Patients with significant aortic root dilation should be considered for surgical intervention, regardless of symptoms. Current approaches include aortic root replacement, such as composite valve graft (CVG) or valve-sparing aortic root replacement.

• Management of other complications:

  • Due to the risk of lens dislocation (ectopia lentis), cataracts, glaucoma, and retinal detachment, annual ophthalmologic evaluations and targeted treatments are recommended.
  • Severe mitral regurgitation with symptoms, progressive left ventricular dilation, or systolic dysfunction may warrant mitral valve repair or replacement.
  • Patients with scoliosis may require bracing or spinal corrective surgery.

Finally, before undergoing surgery, MFS patients should strictly avoid strenuous activities. Low-to-moderate intensity leisure exercises (e.g., golf, hiking) are permitted, but high-intensity sports like rock climbing, surfing, or weightlifting must be avoided.

DIET & LIFESTYLE

How long can a patient with Marfan syndrome live?

Patients with this disease often have cardiovascular system involvement, which affects life expectancy, with most deaths occurring in young or middle-aged individuals. The majority of patients die from cardiovascular complications. After aortic damage occurs, most patients die within 2 years.

What should patients with Marfan syndrome pay attention to in daily life?

Patients with Marfan syndrome should primarily focus on the intensity of physical activity. It is generally recommended that MFS patients avoid strenuous exercise and engage in moderate recreational activities, as detailed below:

• Activities that are not recommended and strongly discouraged include: isometric exercises (e.g., weightlifting, sit-ups, pull-ups, push-ups), ice hockey, rock climbing, windsurfing, and surfing. Scuba diving should also be avoided due to the increased risk of pneumothorax from barotrauma.

• Activities requiring individual assessment before participation include: basketball (full-court and half-court), racquetball, squash, running, skiing (downhill and cross-country), singles tennis, touch/flag football, soccer, baseball, softball, cycling, lap swimming, motorcycle riding, and horseback riding.

• Potentially permitted low-to-moderate intensity recreational activities (non-competitive) include: bowling, golf, skating (excluding ice hockey), shallow diving, brisk walking, treadmill exercise, or stationary cycling; light hiking, doubles tennis, etc.

For children with MFS, parents should discuss with physical education teachers to agree on appropriate activity levels and ensure feasible sports participation under guidance. A blanket ban on physical activity is not advisable, as merely observing peers is detrimental to the child and may foster feelings of shame. If the school is unwilling or unable to provide suitable and tolerable exercise options, the child should be allowed to participate in appropriate activities at another sports facility.

PREVENTION

How Can Patients with Marfan Syndrome Avoid Having a Baby with Health Issues?

To prevent the birth of a child with health problems, chorionic villus sampling at 10–12 weeks of pregnancy or amniocentesis at 16 weeks can be performed. These procedures can detect whether the baby carries the pathogenic gene. However, due to the phenotypic variability of Marfan syndrome, identified mutations may not always definitively indicate life-threatening risks. As a result, many couples struggle with the decision of whether to terminate the pregnancy.

With advancements in assisted reproductive technology, the third-generation "test-tube baby" technique—preimplantation genetic diagnosis (PGD)—offers a new solution to this challenge. PGD provides significant hope for many infertile couples and individuals with genetic disorders.

In 1996, microsatellite polymorphism was used abroad to perform PGD for a couple with Marfan syndrome, resulting in the world's first PGD-derived baby unaffected by the condition. Since then, clinical applications in this field have increased. As PGD technology for Marfan syndrome becomes more refined, more patients are likely to choose PGD to fulfill their dream of having healthy offspring.