In a 6‑week‑old infant with a unilateral absent red reflex (leukocoria) in the left eye and normal development, what is the most likely diagnosis?

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Retinoblastoma

In a 6-week-old infant presenting with unilateral leukocoria (absent red reflex) and normal development, retinoblastoma is the most likely diagnosis and must be ruled out urgently, as it accounts for approximately half of all leukocoria cases in infants. 1, 2, 3

Why Retinoblastoma is the Primary Concern

Leukocoria in infants is always a danger signal requiring immediate ophthalmologic evaluation. 3 The key diagnostic considerations are:

  • Retinoblastoma is responsible for 50% of leukocoria cases in this age group, making it the single most critical diagnosis to exclude given its life-threatening nature 2, 3
  • Bilateral retinoblastoma typically presents at 18-24 months, but unilateral disease presents around 36 months on average 4, 5 — however, hereditary cases can present much earlier, even in the newborn period 4
  • The median age at diagnosis for unilateral retinoblastoma is 2 years (24 months), but presentation at 6 weeks, while earlier than typical, does not exclude the diagnosis 2

Why the Other Options Are Less Likely

Congenital Cataract (Option C)

  • Congenital cataracts are listed as a cause of leukocoria but represent a lens abnormality rather than a retinal malignancy 1
  • While possible, cataracts do not carry the same mortality risk and can be differentiated on ophthalmologic examination 1

Toxocariasis (Option A)

  • Ocular toxocariasis (larval granulomatosis) is indeed a recognized cause of leukocoria 1, 3
  • However, it typically presents later in childhood (ages 3-8 years) and is associated with exposure to contaminated soil or puppies 3
  • At 6 weeks of age with no mentioned exposure history, this is far less likely than retinoblastoma

Immediate Diagnostic Approach

The diagnosis is established by fundoscopic examination under sedation/anesthesia by a pediatric ophthalmologist, not by tissue biopsy. 1, 6 The evaluation should include:

  • Urgent ophthalmologic examination within 24 hours to maximize visual outcomes and enable early detection 4, 7
  • Fundoscopy under anesthesia is the gold standard for complete evaluation 5, 6
  • Ocular ultrasound performed by the ophthalmologist can help confirm the diagnosis 1, 6
  • MRI of head and orbits with and without IV contrast is the most useful imaging modality for evaluating suspected retinoblastoma, assessing optic nerve extension, and detecting intracranial spread 1
  • Avoid CT scanning to reduce radiation exposure, especially since 15% of unilateral cases are hereditary and these children face significantly increased risk of radiation-induced second malignancies 7, 8

Critical Management Considerations

All children diagnosed with retinoblastoma—whether unilateral or bilateral—require germline RB1 genetic testing regardless of family history. 7, 5 This is essential because:

  • Approximately 15% of unilateral retinoblastoma cases are hereditary despite appearing sporadic 7, 5
  • Up to 40% of hereditary cases arise from de novo germline mutations without any prior family history 7
  • Bilateral disease always represents hereditary retinoblastoma and requires genetic counseling regardless of test results 1, 7, 5

Common Pitfalls to Avoid

  • Do not delay referral based on the infant's young age or normal development—retinoblastoma can present in early infancy 4
  • Do not assume absence of family history excludes hereditary disease—de novo mutations are common 7, 5
  • Do not order CT as initial imaging—MRI is superior and avoids radiation exposure in a potentially hereditary cancer predisposition syndrome 1, 8
  • Do not dismiss leukocoria as benign until retinoblastoma is definitively excluded by expert ophthalmologic examination 3

Answer: B - Retinoblastoma

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Retinoblastoma.

Orphanet journal of rare diseases, 2006

Guideline

Retinoblastoma Onset and Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Retinoblastoma Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Retinoblastoma: an overview.

Indian journal of pediatrics, 2012

Guideline

Guidelines for Surveillance and Genetic Testing in Childhood Retinoblastoma

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Retinoblastoma: diagnosis and management--the UK perspective.

Archives of disease in childhood, 2015

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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