Marfan Syndrome

Question 1

What is the inheritance pattern for Marfan?

Answer 1

AD

75% AD 25% sporadic

Question 2

What is the genetic defect for Marfan?

Answer 2

Fibrillin (FBN1) mutation chrom. 15q21.1

Question 3

What is the pathogenesis of Marfan?

Answer 3

Reduced fibrillin-containing microfibrils in elastic tissue results in fewer binding sites for transforming growth factor beta (TGF-beta) and overactive TGF-beta signaling in tissue (role in vascular wall modeling)

Question 4

What is the recurrence risk of Marfan?

Answer 4

50% if parent affected

<1% if parents unaffected

Question 5

What are the associated medical findings with Marfan?

Answer 5

1. Tall stature, long limbs - dolichostenomelia, arachnodactyly
   a) Disproportionate upper-to-lower segment ratio (<0.85 in adults)
   b) Increased arm span-to-height ratio (>1.05)
2. Cardiac:
   a) Aortic root dilatation/dissection
   b) Mitral valve prolapse and/or regurgitation
3. Ocular:
   a) Ectopia lentis
   b) Myopia
   c) Cataracts
   d) Glaucoma
   e) Retinal detachment
   f) Exotropia/strabismus
4. Apical blebs –> Increased spontaneous pneumothorax
5. Connective tissue involvement
   a) Pectus deformities
   b) Scoliosis
   c) Dural ectasia (weakness of spinal cord sac)
   d) Joint hyperextensibility
   e) Contractures
   f) Increased hernias
   g) Striae,
6. *Neonatal Marfan Syndrome is often fatal in first year of life due to CHF

Question 6

What are the developmental outcomes for Marfan?

Answer 6

1. Typical cognitive development
2. Motor development may be affected by joint hyperextensibility
3. Increased risk for psychosocial morbidity
   a) Associated with individual and family response to increased risk of death

Question 7

What is the DDx for Marfan?

Answer 7

1. Homocystinuria: Often Rx Vit. B6. Plasma homocysteine and serum amino acids
   indicated for all patients with clinically normal parents
2. Loeys-Dietz Syndrome - dilated tortuous aorta, cleft palate or bifid uvula,
   hypertelorism, occasional craniosynostosis, arachnodactyly, often translucent skin
3. Stickler Syndrome - marfanoid habitus, cleft palate including Robin Sequence, mid-facial hypoplasia, hearing loss, severe myopia with risk for cataract and retinal detachment, spondyloepiphyseal dysplasia on skeletal radiographs
4. Familial Thoracic Aortic Aneurysms & Dissection
5. Ehlers-Danlos Syndrome
6. Congenital Contractural Arachnodactyly (Beals Syndrome) – joint contractures,
   arachnodactyly, crumpled ear, mitral valve prolapse with regurgitation, occasional
   aortic root dilatation.
7. Other connective tissue disease

Question 8

What are the recommendations for Marfan?

Answer 8

1. Cardiovascular
   a) Yearly echocardiography
   b) Beta-blockers reduce hemodynamic stress on aortic wall
   c) Surgical aortoplasty (aortic diameter > 5cm or smaller diameter but rapid
   progression of dilatation in very young children)
   d) Mitral and aortic valve replacement for progressive MI, AISBE
   prophylaxis essential
   e) Avoid competitive sports and isometric exercise
2. Ocular: Experienced Peds Ophthalmology is essential
   a) Lens dislocation may require surgical lens implantation
3. Progressive scoliosis: surgical stabilization
4. Severe pectus excavatum may limit cardiopulmonary function

Question 9

What are the major clinical manifestations of Marfan Syndrome?

Answer 9

1. Progressive aortic dilatation –> aortic dissection
2. Mitral valve prolapse –> mitral incompetence
3. Eye findings incld. ectopia lentis and myopia
4. Skeletal features incld. joint laxity, arachnodactyly, scoliosis