Marfan Syndrome

Marfan syndrome is a genetic disorder that affects the body's connective tissue, which provides strength and flexibility to structures throughout the body. This condition most seriously affects the heart and blood vessels, but also involves the eyes, bones, joints, and lungs. With proper management and monitoring, people with Marfan syndrome can live long, productive lives, though life-threatening complications can develop if the condition goes undiagnosed or untreated.

⚠️ Medical Emergency

Seek immediate emergency care for: sudden severe chest or back pain (may indicate aortic dissection), severe shortness of breath, rapid heartbeat with chest pain, or sudden vision loss. These may be life-threatening complications requiring emergency treatment.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Marfan Syndrome

Marfan syndrome is caused by a mutation in the FBN1 gene, which provides instructions for making fibrillin-1, a protein essential for forming elastic fibers in connective tissue. This defect weakens connective tissue throughout the body, leading to features ranging from mild to life-threatening.

Key Facts

  • Affects 1 in 5,000 people worldwide
  • Inherited in autosomal dominant pattern
  • 25% of cases are new mutations
  • Affects all races and ethnicities equally
  • Variable expression even within families
  • Life expectancy near normal with proper care

Body Systems Affected

  • Cardiovascular: Most serious complications
  • Skeletal: Distinctive physical features
  • Ocular: Vision problems
  • Pulmonary: Lung issues
  • Skin: Stretch marks
  • Dural: Spinal covering abnormalities

Signs and Symptoms

Marfan syndrome features vary greatly, even among family members. Some people have mild symptoms, while others experience life-threatening complications.

Cardiovascular Features

  • Aortic dilation: Progressive enlargement of aorta
  • Aortic regurgitation: Leaky aortic valve
  • Mitral valve prolapse: Floppy mitral valve
  • Aortic dissection: Tear in aortic wall (emergency)
  • Heart murmur: From valve problems
  • Arrhythmias: Irregular heartbeats
  • Heart failure: In severe cases

Skeletal Features

  • Tall stature: Above average height for family
  • Arm span exceeds height: By >5cm
  • Long fingers (arachnodactyly): Spider-like fingers
  • Flexible joints: Hypermobility
  • Chest deformities:
    • Pectus excavatum (sunken chest)
    • Pectus carinatum (protruding chest)
  • Scoliosis: Curved spine
  • Flat feet: Pes planus
  • High-arched palate: Crowded teeth

Ocular Features

  • Lens dislocation (ectopia lentis): In 60%
  • Severe myopia: Nearsightedness
  • Early cataracts: Clouding of lens
  • Glaucoma: Increased eye pressure
  • Retinal detachment: Risk increased
  • Strabismus: Eye misalignment

Other Features

  • Stretch marks: Without weight changes
  • Hernias: Inguinal or incisional
  • Dural ectasia: Weakening of spinal sac
  • Spontaneous pneumothorax: Collapsed lung
  • Sleep apnea: Due to facial structure
  • Easy bruising: Fragile blood vessels

Clinical Signs

Wrist and Thumb Sign

  • Thumb overlaps pinky when wrapping hand around wrist
  • Positive in many Marfan patients

Steinberg Sign

  • Thumb extends beyond palm edge when folded
  • Indicates long fingers

Causes and Genetics

Genetic Cause

  • FBN1 gene mutation: On chromosome 15
  • Over 3,000 different mutations identified
  • Produces defective fibrillin-1 protein
  • Disrupts elastic fiber formation
  • Affects TGF-β signaling

Inheritance Pattern

  • Autosomal dominant:
    • One mutated copy causes disease
    • 50% chance of passing to children
    • Affects males and females equally
  • New mutations:
    • 25% have no family history
    • Associated with advanced paternal age
    • Can then be passed to offspring

Variable Expression

  • Same mutation can cause different severity
  • Features vary within families
  • Cannot predict severity from genetics
  • Environmental factors may play role

Diagnosis

Revised Ghent Criteria (2010)

Diagnosis based on combination of clinical features, family history, and genetic testing:

Major Criteria

  • Aortic root dilation or dissection
  • Ectopia lentis (lens dislocation)
  • FBN1 mutation known to cause Marfan
  • Family history of Marfan syndrome

Clinical Evaluation

  • Physical examination:
    • Height, arm span, body proportions
    • Joint flexibility
    • Skin examination
    • Cardiac auscultation
  • Cardiac evaluation:
    • Echocardiogram (essential)
    • ECG
    • MRI or CT for aorta
  • Eye examination:
    • Slit-lamp exam
    • Dilated fundus exam
  • Skeletal assessment:
    • X-rays for scoliosis
    • Hip evaluation

Genetic Testing

  • FBN1 gene sequencing
  • Detects mutations in 70-93% of cases
  • Helpful for family screening
  • Cannot rule out diagnosis if negative

Differential Diagnosis

  • Loeys-Dietz syndrome
  • Ehlers-Danlos syndrome (vascular type)
  • Homocystinuria
  • MASS phenotype
  • Familial thoracic aortic aneurysm

Treatment and Management

Management focuses on preventing complications and treating problems as they arise:

Cardiovascular Management

Medications

  • Beta-blockers:
    • First-line therapy
    • Reduces aortic stress
    • Slows aortic dilation
    • Started at diagnosis
  • ARBs (Losartan):
    • Alternative or addition to beta-blockers
    • May slow aortic growth
    • Under investigation

Surgery

  • Prophylactic aortic root replacement:
    • When aorta reaches 5.0 cm
    • Earlier if rapid growth or family history
    • Valve-sparing techniques preferred
  • Emergency surgery:
    • For aortic dissection
    • High mortality if delayed

Orthopedic Management

  • Scoliosis:
    • Bracing for moderate curves
    • Surgery for severe curves (>45°)
  • Chest deformities:
    • Surgery if cardiopulmonary compromise
    • Cosmetic concerns
  • Joint problems:
    • Physical therapy
    • Joint protection strategies

Ophthalmologic Care

  • Annual eye exams
  • Glasses or contacts for myopia
  • Surgery for severe lens dislocation
  • Monitor for glaucoma and cataracts
  • Urgent care for retinal symptoms

Activity Restrictions

  • Avoid:
    • Contact sports
    • Competitive sports
    • Isometric exercises
    • Heavy lifting
    • Activities with rapid acceleration/deceleration
  • Encouraged:
    • Low-intensity aerobic exercise
    • Walking, swimming, cycling
    • Keep heart rate <100 bpm

Lifelong Monitoring

Cardiac Surveillance

  • Annual echocardiogram: Monitor aortic size
  • MRI/CT: Every 3-5 years or as needed
  • More frequent if:
    • Aortic dilation present
    • Rapid growth detected
    • Approaching surgical threshold

Other Monitoring

  • Annual ophthalmologic exam
  • Orthopedic evaluation as needed
  • Pulmonary function if symptoms
  • Sleep study if sleep apnea suspected

Family Screening

  • First-degree relatives should be evaluated
  • Genetic counseling recommended
  • Prenatal diagnosis available
  • Children need regular monitoring

Special Considerations

Pregnancy

  • High-risk pregnancy: Requires specialized care
  • Aortic dissection risk: Highest in third trimester/postpartum
  • Pre-pregnancy counseling: Essential
  • Recommendations:
    • Aortic imaging before pregnancy
    • Avoid if aorta >4.0 cm
    • Monthly cardiac monitoring
    • Consider early delivery

Dental Care

  • High-arched palate causes crowding
  • Increased risk of endocarditis
  • May need antibiotic prophylaxis
  • Regular dental care important

Emergency Preparedness

  • Wear medical alert identification
  • Carry emergency information card
  • Educate family about dissection signs
  • Have emergency plan

Prognosis and Outlook

Life Expectancy

  • Without treatment: Average 32 years (historical)
  • With modern care: Near-normal lifespan
  • Key factors:
    • Early diagnosis
    • Regular monitoring
    • Preventive surgery
    • Activity modification

Quality of Life

  • Most lead normal, productive lives
  • Can have careers and families
  • Activity limitations may affect some
  • Psychological support helpful
  • Support groups available

Future Directions

  • Gene therapy research ongoing
  • New medications under study
  • Improved surgical techniques
  • Better understanding of TGF-β pathway