🔍 Question

An 11-year-old boy is brought to the physician for evaluation of scoliosis. His mother reports that he appears to lean to one side even when attempting to sit or stand upright. The boy has a history of myopia (nearsightedness) and upward lens dislocation, for which he wears corrective glasses. He is otherwise healthy and performs well academically. His family history is notable for scoliosis and vision problems in his father, who passed away last year due to "heart problems."

Physical Examination Findings:

• General Appearance: Tall stature for his age, long arms and legs, minimal subcutaneous fat, and a long, thin face.

• Craniofacial Features: High-arched palate with crowded teeth.

• Ocular Findings: Upward dislocation of the lens (consistent with his history of lens dislocation

• Musculoskeletal Features: Joint hypermobility, skin hyperelasticity, and a 15-degree thoracic scoliosis.

• Cardiac Findings: A diastolic murmur heard in the aortic area.

• Extremities: Long, thin fingers and a prominent sternum.

Question:
Based on the clinical presentation and physical examination findings, which of the following is the most likely etiology of this patient's condition?

Options:

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

Correct Answer 🎯: C (Mutation of the fibrillin-1 gene)

Key Insights (🧠):

• Tall stature, long limbs, joint hypermobility, and scoliosis suggest a connective tissue disorder.

• Lens dislocation (upward) and aortic murmur point toward systemic connective tissue involvement.

• Family history of similar features and heart problems suggests an autosomal dominant inheritance pattern.

⚙️

FBN1 Gene Mutation (Chr 15) →
⬇
Defective Fibrillin-1 (Structural glycoprotein that provides scaffold for elastin)
⬇
Elastin Disorganization in Connective Tissues
⬇
Aorta, Ocular, and Skeletal System Weakness
⬇
🧠 Cardiovascular Manifestations

• Aortic Root Dilatation ⬆
  ⬇
  Aortic Regurgitation (Diastolic Murmur)
  ⬇
  ↑ Risk of Aortic Dissection (Father’s "heart problems")

🧠 Ocular Manifestations

• Zonular Fiber Weakness ⬇
  ⬇
  Upward Lens Dislocation (Ectopia Lentis)
  ⬇
  Myopia ⬆ (Near-sightedness)

🧠 Skeletal Manifestations

• Defective Periosteal Bone Formation ⬇
  ⬇
  Tall Stature, Long Limbs, Arachnodactyly
  ⬇
  Joint Hyperflexibility, Scoliosis, Sternum Deformity

How To Approach this Question? 🏗️

🧠 Clinical Clues from the Case:

• Marfanoid Features (Tall, long limbs, scoliosis, joint hypermobility)

• Lens Dislocation 🔍 (Direction matters: Upward → Marfan, Downward → Homocystinuria)

• Diastolic Murmur ⚙ (Aortic root dilation → Risk of dissection 🏥)

• Family History 📜 (Father with scoliosis & "heart problems" → Aortic pathology suspicion)

⚖️ Explanation of Other Differentials

📝 Flashcards

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Dr. Shoaib Ahmad