An 11-year-old boy is brought to the physician for evaluation of scoliosis. His mother noticed that he always seems to be leaning even when he tries to sit or stand upright. The boy has a history of myopia and upward lens dislocation for which he wears corrective glasses. He otherwise has been healthy and doing well in school. His father had scoliosis and vision problems and died from "heart problems" last year. Physical examination shows a boy with a long face, high arched palate with crowded teeth, and upward dislocation of the lens. He has a tall stature for his age; long arms and legs with minimal subcutaneous fat; long, thin fingers; and a prominent sternum. Joint hypermobility, skin hyperelasticity, and 15 degrees of thoracic scoliosis are seen. A diastolic murmur is heard in the aortic area. Which of the following is the most likely etiology of this patient's condition?

A. Cystathionine synthase deficiency

B. Defective collagen production

C. Mutation of the fibrillin-1 gene

D. Mutation of the fibrillin-2 gene

E. Nondisjunction resulting in an extra X chromosome

Answer: Mutation of fibrillin-1 gene

Marfan Syndrome

• Most likely etiology for this patient’s presentation with scoliosis, long limbs, upward lens dislocation, and aortic murmur.

• Caused by mutation in fibrillin-1 gene leading to impaired connective tissue.

Fibrillin-1 gene mutation (chromosome 15)
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Fibrillin-1 is a glycoprotein crucial for forming elastic fibers in connective tissue
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Defective fibrillin-1 → impaired connective tissue
⬇️

Skeletal System

• Tall stature, long limbs (arachnodactyly), scoliosis
  

• High arched palate with crowded teeth
  

• Joint hypermobility (elastin affected)
  

  ⬇️

Ocular System

• Upward lens dislocation (ectopia lentis)

  ⬇️
  

Cardiovascular System

• Aortic dilation, aortic root aneurysm, diastolic murmur
  ⬇️

• Weakened aortic walls (loss of structural integrity) → leads to risk of aortic dissection or rupture

  

  Image: Cleveland

  
  

  ⬇️

Family History of similar findings
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🧠 Correct Answer: C. Mutation of the fibrillin-1 gene

🧠 Explanation for Other Answers

A. Cystathionine synthase deficiency

• Homocystinuria presents with similar ocular findings (lens dislocation) but also involves intellectual disability, thromboembolic events, and vascular disease, which are not present here
  ⬇️

B. Defective collagen production

• Ehlers-Danlos syndrome (skin hyperelasticity, joint hypermobility) but does not involve upward lens dislocation, tall stature, or scoliosis seen in this case
  ⬇️

D. Mutation of the fibrillin-2 gene

• Fibrillin-2 mutations are associated with Congenital Contractural Arachnodactyly (Beals syndrome)

• Presents with similar features to Marfan, but lacks aortic involvement and features like contractures (which this patient lacks)
  ⬇️

E. Nondisjunction resulting in an extra X chromosome

• Klinefelter syndrome is characterized by tall stature, but does not have ocular involvement, scoliosis, or cardiovascular abnormalities like Marfan Syndrome.

Flashcards

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