What Is Marfan Syndrome?

Last Updated on July 31, 2019

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

Marfan syndrome results from mutations in the fibrillin-1 gene on chromosome 15, which encodes for the glycoprotein fibrillin.

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.

Occurrence

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.]

Skeletal System

Major criteria

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 – 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 acetabulum invaginates the pelvic cavity]

Minor criteria

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.

Ocular findings

The major criterion is ectopia lentis [lens dislocation]

Minor criteria

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
Nearsightedness
Glaucoma in < 50 years old patients
Retinal detachment

At least 2 minor criteria must be present.

Cardiovascular

Major criteria

Aortic root dilatation
Aortic dissections involving the ascending aorta

Minor criteria

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 an involved system

Pulmonary

Only minor criteria

Spontaneous pneumothorax
Apical blebs on chest radiograph are noted.

A minor criterion must be present to label the involvement of this system

Skin & Integument

Only minor criteria

Stretch marks [Shoulder, mid back, and thighs]
A recurrent or incisional hernia

Dural

Only one major criterion is defined- Dural ectasia

Laboratory Studies

Molecular studies of the fibrillin gene should be carried out in patients wherein patients in whom Marfan syndrome is suspected.

Imaging in Marfan Syndrome

Radiography

Chest radiographs may show apical blebs [Pockets of fluid]. It may also show enlargement of the aortic and cardiac silhouette and aid in the diagnosis of aortic dissection.
Skeletal X-rays might reveal the skeletal deformities mentioned earlier

Echocardiography

Aids in the diagnosis and management of aortic root dilatation.

CT and MRI

MRI can reveal aortic dissection and dural ectasia.