Marfan Syndrome
The Classic Connective Tissue Disorder
Ghent Criteria
Critical Must-Knows
- FBN1 Gene: Fibrillin-1 mutation.
- Aortic Root: Annual echo screening essential.
- Scoliosis: Common, may be progressive.
- Protrusio Acetabuli: Characteristic finding.
- Dural Ectasia: Expand the dural sac.
Examiner's Pearls
- "FBN1 mutation
- "Aortic root is main mortality cause
- "Scoliosis screening needed
- "Protrusio is characteristic
Clinical Imaging
Imaging Gallery
Cardiac Monitoring
Aortic root dilation and dissection are the main causes of death in Marfan Syndrome.
- Annual echocardiogram is MANDATORY.
- Beta-blockers reduce aortic root growth.
- Avoid strenuous/contact sports.
- Pre-operative cardiac clearance for scoliosis surgery.
Skeletal Features in Marfan
| Feature | Description | Management |
|---|---|---|
| 30-50% | Bracing, surgery if progressive | |
| Excavatum or Carinatum | Surgical repair if severe | |
| Medial protrusion of acetabulum | Usually observation | |
| Flat feet, hypermobile | Orthotics |
Marfan Features
Memory Hook:MARFS - Marfanoid, Aortic, Retinal, FBN1, Scoliosis.
Skeletal Features
Memory Hook:PPPS - Pectus, Protrusio, Pes planus, Scoliosis.
Ghent Criteria
Memory Hook:GHENT criteria - Genetics, Heart, Eyes, Numbers, Tests.
Overview/Epidemiology
Marfan Syndrome is a connective tissue disorder.
- Genetics: Autosomal dominant. FBN1 (Fibrillin-1) gene on chromosome 15.
- Incidence: 1 in 5,000-10,000.
- Pathophysiology: Defective fibrillin leads to abnormal elastic fibers and increased TGF-β signaling.
- Diagnosis: Ghent criteria (revised 2010).
Pathophysiology and Mechanisms
Connective Tissue Abnormalities
- Fibrillin is a component of elastic fibers.
- Abnormal elastic fibers affect aorta, ligaments, lens zonules.
- Increased TGF-β signaling contributes to aortic disease.
Why Scoliosis Develops
- Ligamentous laxity + abnormal connective tissue.
- Curves may resemble idiopathic scoliosis but can be more severe.
Classification Systems
Ghent Criteria (Revised 2010)
Major Features:
- Aortic root dilation (Z-score ≥2) or dissection.
- Ectopia lentis (lens dislocation).
- FBN1 mutation.
- Systemic score ≥7 (skeletal features).
- Dural ectasia.
Diagnosis: 2 major features from different systems OR FBN1 + 1 major.
Clinical Assessment
History:
- Family history.
- Cardiac symptoms (palpitations, chest pain).
- Visual symptoms.
- Musculoskeletal symptoms.
Physical Exam:
- General: Tall, thin, arm span greater than height.
- Arachnodactyly: Long fingers. Walker-Murdoch (thumb overlaps fifth finger around wrist). Steinberg (thumb extends beyond ulnar border).
- Pectus: Excavatum or carinatum.
- Spine: Scoliosis.
- Hips: Protrusio (limited IR).
- Feet: Pes planus, hindfoot valgus.
- Eyes: Slit lamp for lens dislocation.
Investigations
Genetic Testing:
- FBN1 mutation: Confirmatory.
Cardiac:
- Echocardiogram: Aortic root measurement. Annual.
Ophthalmology:
- Slit lamp: Lens dislocation.
Imaging:
- Spine X-ray: Scoliosis.
- Pelvis X-ray: Protrusio acetabuli.
- MRI Spine: Dural ectasia.
Management Algorithm
Cardiac Management
- Annual Echo: Monitor aortic root.
- Beta-Blockers: Reduce aortic root growth rate.
- Losartan: May also help (TGF-β blocker).
- Surgery: Aortic root replacement if dilated.
- Activity Restriction: No contact sports, strenuous activity.
Surgical Techniques
Posterior Spinal Fusion
Indications: Progressive scoliosis greater than 40-50 degrees.
Pre-op: Cardiac clearance. Echo. Avoid hypotension.
Technique: Standard posterior fusion. Curves often longer than idiopathic.
Considerations: Dural ectasia may cause CSF leak. Blood pressure management critical.
Complications
| Complication | Context | Management |
|---|---|---|
| Aortic Dissection | Perioperative | Careful BP control |
| Dural Ectasia | Spine surgery | CSF leak risk |
| Hardware Failure | Weak bone/tissue | Monitor |
Postoperative Care
- Cardiac Monitoring: Blood pressure control.
- Standard Spine Protocol: Mobilization, physiotherapy.
Outcomes/Prognosis
- Life Expectancy: Reduced (median 40-50 years historically). Improved with aortic monitoring and surgery.
- Orthopaedic: Scoliosis surgery outcomes similar to idiopathic.
Evidence Base
- Revised Ghent criteria
- Simplified diagnosis
- Emphasis on aortic root
- Scoliosis in Marfan
- 30-50% incidence
- Similar to idiopathic
- Losartan vs atenolol for aortic root
- Both effective
- No difference in growth rate
- Comprehensive Marfan review
- Multidisciplinary management
- Genetic testing
- Scoliosis surgery outcomes in Marfan
- Similar correction to idiopathic
- Higher complication rate (dural tear)
Viva Scenarios
Practice these scenarios to excel in your viva examination
Scoliosis in Marfan
"15-year-old male with known Marfan Syndrome. Scoliosis of 45 degrees. Aortic root is 4.2cm on recent echo."
This patient has progressive scoliosis requiring surgery. However, the **aortic root is mildly dilated** (normal less than 4.0cm in adults). Pre-operatively, I would obtain **cardiology clearance** with updated echo. I would ensure **blood pressure is well controlled** intraoperatively (avoid hypotension and hypertension). Proceed with **posterior spinal fusion**. Be aware of potential **dural ectasia** (CSF leak risk) and weaker tissues.
Diagnosis of Marfan
"How do you diagnose Marfan Syndrome?"
Diagnosis is based on the **revised Ghent criteria (2010)**. Key features: **Aortic root dilation** (Z-score ≥2), **ectopia lentis** (lens dislocation), **FBN1 mutation**, and **systemic score ≥7** (skeletal features). Diagnosis requires either aortic root + FBN1, OR aortic root + ectopia lentis, OR FBN1 + systemic score ≥7.
Protrusio Acetabuli
"X-ray shows protrusio acetabuli. What is this and how do you manage?"
**Protrusio acetabuli** is medial protrusion of the acetabulum into the pelvis. It is characteristic of Marfan Syndrome. On X-ray, the femoral head protrudes medial to the ilioischial line. Management is usually **observation** as it rarely causes symptoms in youth. In skeletally immature patients with severe progressive protrusio, **triradiate cartilage closure** can be considered. In adults, it may complicate hip arthroplasty.
MCQ Practice Points
Genetics MCQ
Q: What gene is mutated in Marfan Syndrome? A: FBN1 (Fibrillin-1) on chromosome 15.
Cardiac MCQ
Q: What is the main cause of death in Marfan? A: Aortic dissection/rupture.
Orthopaedic MCQ
Q: What hip finding is characteristic of Marfan? A: Protrusio acetabuli.
Eye MCQ
Q: In which direction does the lens dislocate in Marfan? A: Superiorly (upward). Compare to Homocystinuria where it dislocates inferiorly.
Surgical Pearl
Q: What must be done before scoliosis surgery in Marfan? A: Pre-op cardiac clearance with echo is MANDATORY. Watch for dural ectasia (CSF leak risk), curves often longer than idiopathic, and blood pressure control is critical.
Diagnostic Pearl
Q: What are the Walker-Murdoch and Steinberg signs? A: Walker-Murdoch: Thumb overlaps fifth finger when grasping wrist. Steinberg: Thumb extends beyond ulnar border of closed fist. Both indicate arachnodactyly.
Australian Context
- Genetic Testing: Available clinically.
- Marfan Clinics: Multidisciplinary (cardiology, ophthalmology, genetics, orthopaedics).
- Sports Restrictions: No contact sports, limitations on strenuous activity.
- Support: Marfan Association Australia.
MARFAN SYNDROME
High-Yield Exam Summary
GENETICS
- •FBN1 Mutation
- •Chromosome 15
- •Autosomal Dominant
- •Fibrillin-1 defect
CARDIAC
- •Aortic root dilation
- •Annual echo
- •Beta-blockers
- •Main mortality cause
SKELETAL
- •Scoliosis 30-50%
- •Protrusio acetabuli
- •Pectus
- •Pes planus
DIAGNOSIS
- •Ghent criteria
- •Aortic root + FBN1
- •Systemic score ≥7
- •Ectopia lentis
CLINICAL SIGNS
- •Walker-Murdoch sign
- •Steinberg sign
- •Arm span > height
- •Arachnodactyly
SURGERY PEARLS
- •Cardiac clearance first
- •Dural ectasia risk
- •BP control critical
- •Curves often longer
Self-Assessment Quiz
Differential Diagnosis
Marfan-like Syndromes:
| Condition | Gene | Key Differentiator |
|---|---|---|
| Marfan Syndrome | FBN1 | Aortic root dilation, lens UP |
| Loeys-Dietz Syndrome | TGFBR1/2 | Bifid uvula, hypertelorism |
| Homocystinuria | CBS | Lens DOWN, thrombosis, cognitive issues |
| Ehlers-Danlos (Vascular) | COL3A1 | Thin skin, arterial rupture |
| Stickler Syndrome | COL2A1 | Flat face, hearing loss, retinal detachment |
| Beals Syndrome | FBN2 | Crumpled ears, camptodactyly |
Key Distinguishing Features:
- Lens dislocation direction: Marfan UP, Homocystinuria DOWN
- Cognitive function: Normal in Marfan, impaired in Homocystinuria
- Uvula: Normal in Marfan, bifid in Loeys-Dietz
- Gene: FBN1 for Marfan, FBN2 for Beals