Marfan Syndrome

Key Features

Essentials of Diagnosis

• Disproportionately tall stature, thoracic deformity, and joint laxity or contractures

• Ectopia lentis and myopia

• Aortic root dilation and dissection

• Mitral valve prolapse

• Pathogenic variants in the fibrillin gene (FBN1) on chromosome 15

General Considerations

• Autosomal dominant pattern of inheritance

• A systemic connective tissue disease characterized by

  • Abnormalities of the skeletal, ocular, and cardiovascular systems

  • Spontaneous pneumothorax

  • Dural ectasia

  • Striae atrophicae

• Of most concern is disease of the ascending aorta, which is associated with a dilated aortic root

  • Histology of the aorta shows diffuse medial degeneration

• Mitral valve prolapse is common and frequently leads to regurgitation

Clinical Findings

Symptoms and Signs

• Wide variability in clinical presentation

• Affected patients typically are tall, with particularly long arms, legs, and digits (arachnodactyly)

• Commonly, scoliosis and pectus excavatum

• Ectopia lentis, severe myopia, and retinal detachment

• Mitral valve prolapse seen in more than half of patients

• Ascending aortic involvement produces a dilated aortic root, aortic regurgitation, and aortic dissection

• Spontaneous pneumothorax

• Dural ectasia

• Striae atrophicae

Differential Diagnosis

• Tall stature (normal)

• Homocystinuria (with lens dislocation) as a result of cystathionine β-synthase deficiency

• Aortic root disease resulting from other cause, eg, ankylosing spondylitis, syphilis, temporal (giant cell) arteritis, Takayasu arteritis, familial aortic aneurysm, bicuspid aortic valve

• Ehlers-Danlos syndrome

• Loeys-Dietz syndrome

• MASS phenotype

• Idiopathic mitral valve prolapse

Diagnosis

Laboratory Tests

• No simple laboratory test

• DNA analysis can detect pathogenic variants in the fibrillin gene (FBN1) on chromosome 15

• Clinical diagnosis based on family history, detailed ophthalmologic examination (including slit lamp), echocardiography, and physical examination

Treatment

Medications

• Long-term β-adrenergic blockade (eg, atenolol, 1–2 mg/kg orally daily) retards the rate of aortic dilation

• Angiotensin receptor blocker (ARB) treatment is no more effective than β-adrenergic blockade

• Calcium channel blockers, once used as a substitute for β-blockade, are detrimental to the aorta

Surgery

• Prophylactic replacement of the aortic root (and, if necessary, aortic valve) when the diameter reaches 45–50 mm (normal: < 40 mm) prolongs life

• Earlier prophylactic surgery should be considered when there is a strong family history of aortic dissection or when the diameter of the aortic root increases > 3–4 mm per year

• Because of a heightened risk for aortic dissection in the peripartum and postpartum periods, women with an aortic root dimension > 40 mm should consider prophylactic, valve-sparing aortic repair before undertaking a pregnancy

Therapeutic Procedures

• Restriction of vigorous physical exertion protects from aortic dissection

Outcome

Follow-Up