A 2-year-old boy from rural Maharashtra presents with leukocoria and eye pain. Fundoscopy reveals a large intraocular mass with vitreous seeding. Regarding retinoblastoma, all of the following are true EXCEPT:

Explanation

## Inheritance Pattern of RB1 Mutations **Key Point:** The RB1 gene mutation follows an **autosomal dominant** pattern of inheritance in familial retinoblastoma, NOT autosomal recessive. This is a critical distinction that is frequently tested. ## Retinoblastoma: Key Facts | Feature | Details | |---------|----------| | **Unilateral vs Bilateral** | Unilateral ~60%, Bilateral ~40% (heritable form) | | **Inheritance Pattern** | Autosomal **dominant** with incomplete penetrance (~90%) | | **RB1 Gene** | Tumor suppressor gene; loss of both alleles required ("two-hit" hypothesis) | | **Familial Risk** | 50% of offspring of affected individuals | ## Clinical Presentations & Management **High-Yield:** The classic presentation is **leukocoria** (white pupil reflex, "cat's eye reflex") followed by strabismus and eye pain. ### Treatment Algorithms by Stage ```mermaid flowchart TD A[Retinoblastoma diagnosed]:::outcome --> B{Unilateral or Bilateral?}:::decision B -->|Unilateral| C{Advanced disease<br/>no light perception?}:::decision B -->|Bilateral| D[Chemoreduction +<br/>focal therapy]:::action C -->|Yes| E[Enucleation]:::action C -->|No| F[Chemotherapy +<br/>focal therapy]:::action E --> G[Histopathology &<br/>adjuvant Rx]:::action F --> H[Monitor response]:::action ``` **Clinical Pearl:** Enucleation (surgical removal of the eye) is reserved for: - Advanced unilateral disease (International Classification Group D–E) - No light perception or secondary glaucoma - Failed chemoreduction ### Trilateral Retinoblastoma **Mnemonic: TRI-lateral = Bilateral eyes + pineal (third) gland** - Occurs in ~5% of bilateral retinoblastoma cases - Pineal involvement is a **pinealoblastoma** (same histology, different location) - Associated with heritable RB1 mutations - Requires MRI brain screening in all bilateral cases **Warning:** Do NOT confuse trilateral with metastatic disease. Trilateral is a second primary tumor, not metastasis. ## Why Option 1 is Wrong The RB1 mutation is inherited in an **autosomal dominant** pattern, not autosomal recessive. This is the fundamental genetic principle underlying familial retinoblastoma and explains why 50% of offspring of an affected parent carry the mutation. [cite:Parson's Diseases of the Eye 22e Ch 12]