1. Marfan’s Syndrome
Bradley K. Harrison, MD

2. How do we diagnose the Marfan syndrome?
Recognition of both “major” and “minor” clinical manifestations involving:
Skeletal
Cardiovascular
Ocular manifestations
Dura/other
Two systems, including one major should be involved

3. Skeletal findings Major (need 4) Reduced upper to lower segment ratio
Arm span exceeding height
Arachnodactly of fingers and toes with positive wrist and thumb signs
Scoliosis >20% or spondylolisthesis
Pectus carinatum
Pectus excavatum requiring surgery
Reduced extension of elbows (<170°)
Medial displacement of medial malleolus causing pes planus
Protrusio acetabulea

4. Skeletal findings: Major
Reduced upper to lower segment ratio
Arm span exceeding height

5. Skeletal findings: Major
Arachnodactly of fingers and toes with positive wrist and thumb signs
Thumb sign: distal phalanx protrudes beyond border of clenched fist
Wrist sign: thumb and 5th digit overlap

6. Skeletal findings: Major
Scoliosis >20%
Spondylolisthesis
Pectus carinatum
Pectus excavatum requiring surgery
Reduced extension of elbows (<170°)

7. Skeletal findings continued
Minor
Pectus excavatum of moderate severity
Joint hypermobility
High arched palate with crowding of teeth
Facial features
Dolichocephaly
Malar hypoplasia
Enopthalmos
Retrognathia
Down-slanting palpebral fissures

8. Skeletal findings: Minor
High arched palate with crowding of teeth
Dolichocephaly
Retrognathia

9. Cardiovascular findings
Major (need 1)
Dilitation of the ascending aorta involving the sinuses of Valsalva, with or without aortic regurgitation
Dissecting of the ascending aorta

10. Cardiovascular findings: Major
Dilitation of the ascending aorta

11. Cardiovascular findings continued
Minor
Mitral valve prolapse
Mitral regurgitation
Dilitation of the pulmonary artery, in the absence of valvular or peripheral pulmonic stenosis, below age 40
Calcification of mitral annulus below age 40
Dilatation or dissection of descending thoracic or abdominal aorta below age 50

12. Ocular findings Major Minor Ectopia lentis (typically upward)
Flat cornea (measured by keratometry)
Increased axial globe length (u/s)
Hypoplastic iris or hypoplastic ciliary muscle causing decreased miosis
Myopia
Retinal detachment

13. Other findings Major Minor
Dural ectasia affecting the lumbosacral spinal canal
Minor
Spontaneous pneumothorax
Apical blebs
Cutaneous striae distensae
Recurrent or incisional hernias

14. History of the Marfan syndrome
1896: A.B. Marfan described 5 y/o female with long thin legs he characterized as “spider-like”
1914: dislocated lenses
1931: autosomal dominant inheritence
1943: aneurysm of the ascending aorta
1955: comprehensive Marfan’s syndrome
1968: aortic-root replacement

15. The Marfan Syndrome (MFS)
Most common inherited disorder of connective tissue (2-3 per 10,000)
Autosomal dominant
Fibrillin-1 gene (FBN1)
located on chromosome 15q21
75% inherited, 25% de novo mutation
FBN1 penetrance high
Phenotypic expression is extremely variable
Without a particular gender, racial, geographic, or ethnic predilection

16. MFS continued Differential Diagnosis
Homocystinuria: Marfanoid habitus, ectopia lentis, mental retardation, osteoporosis
Serum amino acid analysis
MASS phenotype: Mitral valve prolapse, mild aortic dilatiation, striae atrophica, skeletal involvement
Ehlers-Danlos syndrome: marked joint hypermobility, paparaceous scars, mitral prolapse
Stickler’s syndrome: tall stature, retrognathia, mitral valve prolapse, midfacial hypoplasia, retinal detachment
Beil’s syndrome (congenital contractural arachnodactly): arachnodactly, joint contractures, scoliosis, crumpled ear malformation

17. MFS continued Management
Annual echocardiogram: size and function of heart and aorta
Β-adrenergic blocker: shown to slow progressive widening of the aorta
Aortic root replacement: indicated when aortic root diameter >50-55mm
Annual ophthalmologic examination: screening for strabismus, myopia, lens dislocation
Lifestyle adaptations, restriction of physical activity (4-6 METS), avoidance of competitive sports and weight training
Pregnancy: Β-adrenergic blocker, risk, >50mm elective repair, epidural, C-section