Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

Marfan syndrome is a genetic disorder that affects the body’s connective tissue, which provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. There may be cystic medial necrosis of the media, characterized by fragmentation of elastic laminae with an accumulation of myxoid material in the aortic media, leading to aortic dissection.

About

• Autosomal Dominant Disorder: Inherited connective tissue disease affecting multiple body systems.
• Incidence: Affects approximately 1 in 9,800 individuals, with a risk of aortic disease and heart failure.
• De Novo Mutations: About 27% of cases are due to new mutations rather than inherited.

Genetics

• Autosomal Dominant: Mutation in the FBN1 gene for fibrillin-1 located on chromosome 15.
• Fibrillin-1: Essential for the structural integrity of connective tissues, especially in the aorta and suspensory ligament of the eye.
• Over 800 Mutations: Mutations lead to variable phenotypic expressions even within affected families.

Clinical Features

• Skeletal System:
  • Joint hypermobility, prone to dislocations, progressive kyphoscoliosis.
  • Tall stature with long limbs (dolichostenomelia); arm span to height ratio > 1.05.
  • Arachnodactyly (long, thin fingers) and high-arched palate.
• Ocular Manifestations:
  • Ectopia lentis (upward lens dislocation), severe myopia.
  • Increased risk of glaucoma and cataracts.
• Cardiovascular:
  • Aortic aneurysms and dissection, especially type A dissection above the aortic valve.
  • Mitral valve prolapse (mid-systolic click) and mitral regurgitation.
  • Aortic regurgitation (early diastolic murmur) and risk of heart failure.
• Respiratory System:
  • Pectus excavatum (sunken chest) and pectus carinatum (protruding chest).
  • Increased risk of spontaneous pneumothorax due to apical blebs.
• Other Features: Liver and kidney cysts, inguinal and femoral herniae.

Marfanoid Habitus Differentials

• Homozygous homocystinuria
• Familial aortic aneurysm
• Lujan-Fryns syndrome
• Multiple Endocrine Neoplasia type 2B (MEN2B)

Investigations

• Family History: Assessment of affected relatives is crucial for diagnosis.
• Genetic Testing: Identification of FBN1 mutations confirms the diagnosis.
• Echocardiography: Regular monitoring of the aorta, mitral valve, and cardiac function.
• CT/MRI: Detailed assessment of the heart and aorta for aneurysms and dissection risks.
• Ghent Diagnostic Criteria: Used to establish a diagnosis based on clinical features.
• Ophthalmologic Examination: Regular monitoring for lens dislocation and myopia.

Management

• Regular Cardiology Review: Annual echocardiograms to monitor aortic root size and mitral valve function.
• Prophylactic Beta-Blockers: Reduce the rate of aortic dilatation when started early in life.
• Aortic Surgery: Prophylactic repair recommended when the aortic root diameter exceeds 50 mm or earlier if family history of dissection is present.
• Acute Aortic Dissection Management: Emergency surgery with Dacron grafts and reimplantation of coronary arteries.
• Mitral Valve Repair: Surgery for severe mitral regurgitation to prevent heart failure.
• Ophthalmologic Care: Regular eye exams to manage refractive errors and monitor for glaucoma or lens dislocation.
• Lifestyle Modifications: Avoid contact sports to reduce the risk of injury to the aorta and other organs.

References

• Marfan Syndrome: Clinical Diagnosis and Management