Marfan syndrome is a genetic disorder of the connective tissue that affects the skeletal, ocular, and cardiovascular systems. It is caused by mutations in the FBN1 gene affecting fibrillin-1, which is important for connective tissue formation. Characteristics include tall stature, long limbs, joint flexibility, eye problems like lens dislocation, and aortic root dilation and risk of aneurysm. Diagnosis involves assessment of these signs against criteria like the Ghent nosology. While there is no cure, management focuses on reducing cardiovascular risk through beta blockers and surgery if needed. A rare neonatal form has very severe effects.

1. MARFAN SYNDROME

2. Contents
● Introduction
● Disease characteristics and Morphology
● Pathogenesis
● Clinical diagnosis
● Others

3. Marfan Syndrome
● Genetic disorder of the connective tissue
● Occurs in about 1 in 5000 people
● Occurs equally in males and females
● Similar rates among different races and in different regions of the world
● Autosomal dominant disorder
● About 3 out of 4 people with Marfan syndrome inherit it from a parent; 1 out of 4
have the condition due to a spontaneous mutation

4. Pathogenesis
● Caused by mutations in the FBN1 gene on chromosome 15, which encodes
fibrillin-1 (a glycoprotein component of the extracellular matrix)
● Fibrillin-1 is essential in formation of elastic fibres found in connective tissues

5. Disease characteristics
Skeletal system
● Tall stature
● Dolichostenomelia, arachnodactyly
(unusually long limbs and fingers)
● Increased risk of abnormal curves in the
spine (e.g. scoliosis)
● Abnormal development of ribs
○ Chest wall deformity (pectus
carinatum or excavatum)
● Abnormal joint mobility
● High arched palate (roof of mouth)

6. Disease characteristics
Cardiovascular system
● Weakened aortic walls
● Dilation of aorta
● Aortic aneurysm
● Aortic dissection
○ Painful, tearing sensation
● Cystic medial degeneration of valves
○ Prolapse of mitral/aortic valves
○ Aortic insufficiency
○ May lead to heart failure

7. Disease characteristics
Eyes
● Lens dislocation (ectopia lentis)
○ Occurs in up to about 80% of MFS
patients and is almost always bilateral
● Increased risk of a detachment or tear in the
retina
● Early-onset glaucoma or cataracts

8. Diagnosis: Ghent nosology (2010)
In the absence of a family history of MFS:
1. Aortic root Z-score ≥ 2 AND ectopia lentis
2. Aortic root Z-score ≥ 2 AND an FBN1 mutation
3. Aortic root Z-score ≥ 2 AND a systemic score* > 7 points
4. Ectopia lentis AND an FBN1 mutation with known aortic pathology
In the presence of a family history of MFS (as defined above):
1. Ectopia lentis
2. Systemic score* ≥ 7
3. Aortic root Z-score ≥ 2

9. Diagnosis: Ghent nosology (2010)
Points for systemic score:
● Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)
● Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)
● Hindfoot deformity = 2 (plain pes planus = 1)
● Dural ectasia = 2
● Protrusio acetabuli = 2
● Pneumothorax = 2
● Reduced upper segment/lower segment ratio AND increased arm/height AND no
severe scoliosis = 1
● Scoliosis or thoracolumbar kyphosis = 1
● Etc.

10. Diagnosis: wrist and thumb signs

11. Medication & Management
● No cure is known
● Management through use of beta blockers, or calcium channel blockers/ACE
inhibitors
○ Lowers blood pressure and reduces strain on aorta
● Aortic/eye/spinal surgery may be required

12. Neonatal Marfan syndrome (nMFS)
● Marfan syndrome occurring during the neonatal
period (in newborns)
● Most severe, life-threatening phenotype of MFS with
a poor prognosis

13. Thanks!