Marfan syndrome is an inherited connective-tissue disorder transmitted as an autosomal dominant trait which has features like tall stature, ectopia lentis, mitral valve prolapse, aortic root dilatation, and aortic dissection.
Pathophysiology of Marfan Syndrome
Marfan syndrome results from mutations in the fibrillin-1 gene on chromosome 15, which encodes for the glycoprotein fibrilin.
Fibrillin is used as a major building block of microfibrils, which constitute the structural components of the suspensory ligament of the lens and serve as substrates for elastin in the aorta and other connective tissues.
Production of abnormal fibrillin-1 monomers from the mutated gene disrupts the multimerization of fibrillin-1 and prevents microfibril formation.
Marfan syndrome affects about 1 in 10,000 individuals. It affects all races and no sex predilection is known.
Presentation & Diagnosis
Diagnosis of Marfan syndrome is based on
- Family history
- Molecular analysis
- Evaluation of six organ systems.
Clinical presentations include
- Delayed motor milestones
- Finding of aortic regurgitation on examination
- Irregular heartbeat
- Acute onset thoracic pain due to aortic dissection
- Low back pain with sensory symptoms like paresthesiae in legs due to dural ectasia [ widening or ballooning of the dural sac[
- Joint pains
- Dyspnea, palpitations, and substernal pain in severe pectus excavatum
- Visual problems including loss of vision[Lens dislocation or retinal detachment.]
- Pectus excavatum that requires surgery
- Arm span–to-height ratio greater than 1.05
- Positive wrist (Walker) and thumb (Steinberg) signs.[Thumb sign- If the thumb, when completely opposed within the clenched hand, projects beyond the ulnar border. Wrist sign – Second, the wrist sign is positive if the distal phalanges of the first and fifth digits of one hand overlap when wrapped around the opposite wrist.]
- Scoliosis greater than 20°
- Reduced extension of the elbows < 170°
- Medial displacement of the medial malleolus, resulting in pes planus [flat fooot]
- Protrusio acetabuli [The acetabulium invaginates the pelvic cavity]
- Moderate Pectus excavatum
- Scoliosis < 20°
- Thoracic lordosis
- Joint hypermobility
- Highly arched palate
- Dental crowding
- Typical facies
At least 2 major criteria or 1 major criterion plus 2 minor criteria must be present for labeling skeletal system involvement.
The major criterion is ectopia lentis [lens dislocation]
- Flat cornea
- Increased axial length of the globe
- Cataract in patients younger than 50 years
- Hypoplastic iris or hypoplastic ciliary muscle that causes decreased miosis
- Glaucoma in < 50 years old patients
- Retinal detachment
At least 2 minor criteria must be present.
- Aortic root dilatation
- Aortic dissections involving the ascending aorta
- Mitral valve prolapse
- Dilatation of proximal main pulmonary artery in the absence of peripheral pulmonic stenosis or other cause.
- Calcification of mitral annulus in patients younger than 40 years of age
- Dilatation of abdominal or descending thoracic aorta patients younger than 50 years of age
A minor criterion must be present to label CVS as involved system
Only minor criteria
- Spontaneous pneumothorax
- Apical blebs on chest radiographare noted.
A minor criterion must be present to label the involement of this system
Skin & Integument
Only minor criteria
- Stretch marks [Shoulder, mid back, and thighs]
- Recurrent or incisional hernia
Only one major criterion is defined- Dural ectasia
Molecular studies of the fibrillin gene should be carried out in patients where in patients in whom Marfan syndrome is suspected.
Imaging in Marfan Syndrome
Chest radiographs may show apical blebs [Pockets of fluid]. It may also show enlargement of the aortic and cardiac silhouette and aid in diagnosis of aortic dissection.
Skeletal xrays might reveal the skeletal deformities mentioned earlier
Aids in the diagnosis and management of aortic root dilatation.
CT and MRI
MRI can reveal aortic dissection and dural ectasia.
Treatment of Marfan Syndrome
Treatment aims at measures to make the life quality better and early detection of problems if they arise. These measures include
- Restriction of physical activity
- Prophylaxis for endocarditis
- Regular ehocardiography at
- Treatment with beta-blockers [for aortic dilatation]
- Management of individual problems
- Pregnancy counseling
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