Marfan Syndrome

Snapshot

• A 30-year-old man with a marfanoid habitus presents for genetic counseling. His father, paternal uncle, and paternal great-grandfather died of sudden cardiac deaths. His father, specifically, suffered from an aortic dissection. As part of this patient’s work-up, he recently had cardiac imaging, which reveals a 5 cm aortic aneurysm. He is sent for further surgical consultation and is tested for suspected Marfan syndrome.

Overview

Introduction

• Clinical definition
  • inherited connective tissue disorder characterized by aortic abnormalities and musculoskeletal deformities
• Epidemiology
  • demographics
    • clinical manifestations typically occur in adulthood
• Pathogenesis
  • fibrillins form a major part of connective tissues and provide structural support and elasticity to blood vessels, skin, and bones
  • abnormalities in fibrillin can result in
    • aortic abnormalities (cystic medial necrosis)
    • ectopic lens (structural weakness in ligaments of the lens)
    • skeletal deformities
• Genetics
  • inheritance pattern
    • autosomal dominant
  • mutations 
    • FBN1 gene is on chromosome 15 and encodes fibrillin-1, a glycoprotein that forms a protective sheath around elastin 
      • elastin is found in multiple parts of the body, including large arteries, skin, lungs, and ligaments
• Prognosis
  • survival has improved with better management of aortic disease
• with early diagnosis and management, patients often have a normal life expectancy

Presentation

• Physical exam
  • skeletal 
    • tall and thin stature 
    • long extremities
      • arm span exceeds height
    • long fingers and toes (arachnodactyly) 
      • thumbnail protrudes beyond ulnar border of hand when crossed (thumb sign)
      • thumb and little finger can encircle wrist (wrist sign)
    • pectus carinatum or excavatum 
    • scoliosis
    • hypermobile joints
  • ocular
    • subluxation of lenses (superior and temporal) 
  • cardiovascular
    • mitral valve prolapse
      • mid-systolic click followed by a late systolic murmur
    • aortic regurgitation
      • diastolic murmur
    • mitral regurgitation
• high-pitched holosystolic murmur

Imaging

• Transthoracic echocardiography
  • indication
    • for all patients to evaluate for cardiac involvement
  • findings
    • mitral or aortic valve abnormalities
• aortic aneurysm or dissection

Studies

• Making the diagnosis
  • based on clinical presentation
• genetic testing is not always necessary but is diagnostic

Differential

• Ehlers-Danlos syndrome 
  • distinguishing factor
    • hyperextensible skin and easy bruising
• middle-sized artery aneurysms > aortic aneurysms

Treatment

• Management approach
  • no curative treatment exists, so treatment is targeted at symptoms
• Conservative
  • avoid high-impact contact sports
    • indication
      • for all patients
• Medical
  • β-blockers or angiotensin receptor blockers
    • indications
      • to halt the progression of aortic root dilation
• Operative
  • aortic aneurysm repair
    • indication
• patients with aneurysms ≥ 4-4.5 cm

Complications

• Aortic dissection
  • most common cause of death
• Congestive heart failure from cardiac valve abnormalities