Clinical Scenario:
A 10-year-old girl is referred from the ophthalmology department for preoperative pediatric and anesthesia assessment before surgery for lens subluxation. On examination, the pediatrician notes that she has a fair complexion and light-colored hair. She is tall and slender with long fingers, and her school performance has been below average.
Ophthalmologic examination reveals inferonasal subluxation of the lens.
Which of the following is the most likely diagnosis?
A. Marfan syndrome
B. Homocystinuria
C. Weill–Marchesani syndrome
D. Ehlers–Danlos syndrome
E. Isolated sulfite oxidase deficiency
Correct answer & Explanation:
Explanation
Correct answer: B. Homocystinuria
Homocystinuria should be considered in a child presenting with ectopia lentis, particularly when it is accompanied by a marfanoid habitus, arachnodactyly and developmental or learning difficulties. Classic homocystinuria may involve the ocular, skeletal, neurologic and vascular systems.
A particularly useful ophthalmologic distinction from Marfan syndrome is the direction of lens displacement. In homocystinuria, ectopia lentis is characteristically inferonasal, whereas Marfan syndrome classically produces superotemporal displacement. The inferonasal displacement in this case therefore supports homocystinuria.
The fair complexion and light-colored/coarse hair are additional clinical clues that can occur in homocystinuria.
The underlying disorder is associated with markedly elevated plasma total homocysteine, often accompanied by increased methionine. Confirmation is made with biochemical testing and, when appropriate, molecular testing.
Why not Marfan syndrome?
Both conditions can produce a marfanoid habitus, arachnodactyly and ectopia lentis, making Marfan syndrome the closest clinical differential. However, the inferonasal direction of lens subluxation, together with the other clinical clues in this case, favors homocystinuria.
Important clinical point
Homocystinuria is particularly important to recognize because affected patients have a significant risk of venous and arterial thromboembolism. This is clinically relevant when a child is being assessed before an ophthalmologic procedure.
Reference
Sacharow SJ, Levy HL. Homocystinuria due to Cystathionine Beta-Synthase Deficiency. GeneReviews®. University of Washington, Seattle. Updated September 25, 2025.
GeneReviews – Homocystinuria due to Cystathionine Beta-Synthase Deficiency
