Makindo Medical Notes.com

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 which is due to fragmentation of elastic laminae with an accumulation of myxoid material in aortic media leading to aortic dissection

About

• Autosomal Dominant inherited connective tissue disease
• Risk of death from aortic disease and heart failure
• Incidence of around 1 in 9800
• 27% of cases arise from new mutation.

Genetics

• Autosomal dominant disease
• Mutation in the gene FBN1 for fibrillin 1 on chromosome 15
• Over 800 distinct mutations exist
• Fibrillin 1 is a component of elastin
• Diagnosis is based on clinical criteria
• Variable phenotypes within affected families

Clinical

• Skeletal
  • Joint hypermobility: Joints that move beyond the normal range of motion.
  • Unstable joints, dislocation of the patella, progressive kyphoscoliosis
  • Tall think wide arm span:long thin arms and legs called dolichostenomelia
  • Arm span to height > 1.05
  • Arachnodactyly - long spidery fingers and high arched palate
• Eyes
  • Ectopia lentis - lens dislocation upwards, myopia, (fibrillin in suspensory ligament of the eye)
  • Myopia: Severe nearsightedness.
  • Glaucoma or cataracts: Increased risk of these eye conditions
• Cardiac
  • Babies/Infants - severe MR and heart failure
  • Aortic aneurysm formation and possible dissection (fibrillin in Aorta)
  • Mitral valve prolapse - mid-systolic click murmur syndrome
  • Aortic regurgitation - early diastolic murmur
  • Type A aortic dissection just above the valve
• Lung
  • Pectus excavatum: A sunken chest.
  • Pectus carinatum: A protruding chest.
  • Spontaneous pneumothorax and apical blebs in 5%
• Liver and kidney cysts on scanning
• Inguinal and femoral herniae

Differential with Marfanoid Habitus

• Homozygous Homocystinuria
• Familial aortic aneurysm
• Lujan-Fryns syndrome
• MEN2B

Investigations

• Assessment of family history, affected relatives
• Genetic Testing: Confirmation of the diagnosis by identifying mutations in the FBN1 gene.
Fibrillin 1 mutation testing if indicated
• Transthoracic echo to look at aorta and mitral valves
• CT/MRI: Assess the heart, aorta, and other affected organs.
• Diagnosis by Ghent diagnostic nosology
• Ophthalmologic Examination: lens dislocation, myopia

Management: Life expectancy approaches that of normal.

• Annual review by specialist/cardiologist with echocardiogram of mitral valve and aortic root.
• Mitral valve surgery: Surgery to repair or replace the mitral valve if it becomes dysfunctional.
• Prophylactic Beta blockade from early age reduces aortic dilatation
• Prophylactic Surgical repair of the Aorta reduces aortic dilatation when aortic root > 50 mm. A history of dissection in the family should encourage earlier surgery.
• Acute Surgery for dissection: insertion of a Dacron graft to the aortic valvular ring after excision of a terminally dilated aorta when diameter reaches 5 cm. This also requires reimplantation of the coronary arteries
• Ophthalmologists to monitor
• Lifestyle Modifications: avoid contact sports to reduce the risk of injury to the aorta and other organs.

References

• Marfan syndrome: clinical diagnosis and management.