Marfan Syndrome

Marfan syndrome is an autosomal dominant connective tissue disorder affecting approximately 1 in 5,000 individuals. It's caused by mutations in the FBN1 gene, which codes for the protein fibrillin-1, essential for elastic fiber formation.

Key Points

• Systemic connective tissue disorder
• Affects multiple organ systems
• Progressive condition requiring lifelong monitoring
• Life-threatening cardiovascular complications
• Early diagnosis crucial for management
• 25% of cases are new mutations

System-Specific Manifestations

Skeletal Features:

• Height and Body Habitus
  • Tall stature
  • Disproportionately long limbs
  • Arm span > height
  • Lower segment ratio altered
• Specific Features
  • Arachnodactyly (long fingers)
    • Positive thumb sign (Steinberg)
    • Positive wrist sign (Walker-Murdoch)
  • Chest Deformities
    • Pectus excavatum
    • Pectus carinatum
    • Asymmetric chest
  • Spine
    • Scoliosis
    • Thoracolumbar kyphosis
    • Dural ectasia
  • Facial Features
    • Long, narrow face
    • Deep-set eyes
    • Downslanting palpebral fissures
    • Malar hypoplasia
    • Retrognathia

Ocular Manifestations:

• Lens Abnormalities
  • Ectopia lentis (lens dislocation)
  • Usually bilateral and superior
  • Present in 60% of patients
• Other Features
  • Myopia
  • Astigmatism
  • Flat cornea
  • Increased axial length
  • Retinal detachment risk

Integumentary Features:

• Skin Characteristics
  • Striae atrophicae
  • Thin, translucent skin
  • Hernias

Revised Ghent Nosology (2010)

Without Family History:

• Aortic Root Criteria (Z-score)
  • ≥2 plus Ectopia Lentis = Diagnosis
  • ≥2 plus FBN1 mutation = Diagnosis
  • ≥2 plus Systemic Score ≥7 = Diagnosis

Systemic Score Components:

• 3 Points Each:
  • Wrist AND thumb sign
  • Pectus carinatum
  • Hindfoot deformity
  • Protrusio acetabuli
• 2 Points Each:
  • Pectus excavatum
  • Reduced US/LS ratio
  • Scoliosis/thoracolumbar kyphosis
  • Reduced elbow extension
• 1 Point Each:
  • Facial features (3/5)
  • Striae
  • Myopia
  • Mitral valve prolapse

Diagnostic Testing:

• Imaging Studies
  • Echocardiogram
  • CT/MRI when indicated
  • Skeletal surveys
  • Ophthalmologic examination
• Genetic Testing
  • FBN1 sequencing
  • Deletion/duplication analysis

Cardiovascular Management

Aortic Manifestations:

• Progressive Dilation
  • Root dilatation most common
  • Regular monitoring essential
  • Z-score measurements
  • Growth rate assessment
• Risk Factors
  • Family history
  • Rate of progression
  • Initial diameter
  • Pregnancy status

Monitoring Protocol:

• Frequency Based on Age/Status
  • Children: 6-12 monthly
  • Adults: Annual if stable
  • More frequent if rapid growth
• Imaging Modalities
  • Echocardiogram
  • CT aorta
  • MR angiogram

Comprehensive Care

Medical Management:

• Cardiovascular
  • Beta blockers
    • First-line therapy
    • Reduces aortic growth rate
    • Improves survival
  • ARBs
    • Alternative/additional therapy
    • Losartan commonly used
• Activity Restrictions
  • Avoid contact sports
  • Moderate aerobic exercise
  • No isometric activities

Surgical Interventions:

• Cardiac Surgery
  • Prophylactic aortic root replacement
  • Valve-sparing procedures
  • Emergency dissection repair
• Orthopedic Procedures
  • Scoliosis correction
  • Pectus repair
  • Joint stabilization
• Ophthalmologic Surgery
  • Lens procedures
  • Retinal detachment repair

System-Specific Complications

Life-Threatening:

• Cardiovascular
  • Aortic dissection
  • Aortic rupture
  • Heart failure
  • Arrhythmias
• Pulmonary
  • Spontaneous pneumothorax
  • Bronchiectasis
  • Sleep apnea

Quality of Life Impact:

• Musculoskeletal
  • Chronic pain
  • Limited mobility
  • Joint instability
• Ocular
  • Vision loss
  • Glaucoma
  • Cataracts

Genetic Aspects

Molecular Basis:

• FBN1 Gene
  • Chromosome 15q21.1
  • Codes for fibrillin-1
  • Over 3000 mutations identified
• Inheritance Pattern
  • Autosomal dominant
  • Variable expressivity
  • Complete penetrance

Genetic Testing Strategy:

• Testing Indications
  • Diagnostic confirmation
  • Family planning
  • Prenatal testing
• Methodologies
  • Next-generation sequencing
  • MLPA analysis
  • Targeted mutation testing

Specific Situations

Pregnancy Management:

• Pre-conception Counseling
  • Risk assessment
  • Genetic counseling
  • Medication adjustments
• Monitoring During Pregnancy
  • Monthly echocardiograms
  • Blood pressure control
  • Activity restrictions

Pediatric Considerations:

• Growth Monitoring
  • Regular measurements
  • Skeletal development
  • Puberty progression
• Educational Support
  • Activity modifications
  • School accommodations
  • Psychosocial support