Describe retinoblastoma with its genetics, presentation and management.

Nature and Genetics

• Retinoblastoma is the commonest primary intraocular malignancy of childhood, arising from primitive retinal cells.
• It occurs in 1 in 15,000 to 20,000 live births, and is curable when caught early and fatal when not.
• The RB1 tumour suppressor gene lies on chromosome 13q14, and the disease is the origin of knudson’S two-hit hypothesis: both copies must be inactivated for a tumour to arise
• Sporadic (60%) — both hits are somatic and occur in a single cell; the disease is therefore unilateral, unifocal, later in onset and not heritable
• Germline (40%) — the first hit is inherited or arises in the germ cell and is present in every cell, so a second hit anywhere in the retina produces a tumour. The disease is therefore bilateral and multifocal, earlier in onset, and heritable with 45% risk to offspring
• Germline patients carry two further risks that determine lifelong care: trilateral retinoblastoma — an associated pineal or suprasellar primitive neuroectodermal tumour.
• Presentation — leucocoria (a white pupillary reflex) in 60%, often first noticed by a parent or in a photograph; and strabismus in 20%, when the tumour destroys central vision
• Any squint IN A child requires A dilated fundus examination, and this is the single most important practical rule in the subject
• IN INDIA the presentation IS often far advanced — with proptosis, orbital extension, buphthalmos, a fungating mass or metastatic disease. Survival in the developed world exceeds 95%.
• Other presentations — a red painful eye with secondary glaucoma; pseudohypopyon of tumour cells; hyphaema; and pseudo-uveitis
• Signs — a white or cream retinal mass with calcification (which is highly characteristic), dilated feeder vessels, vitreous seeds and subretinal seeds, and exudative retinal detachment
• Differential diagnosis OF leucocoria — congenital cataract; coats disease (unilateral, boys, telangiectasia with massive lipid exudation, no calcification); persistent fetal vasculature (unilateral, microphthalmic eye); toxocariasis; retinopathy of prematurity; retinal dysplasia; and endophthalmitis
• Investigation — examination under anaesthesia with indirect ophthalmoscopy, indentation and fundus drawing or photography of both eyes; B-scan ultrasound.
• CT is avoided wherever possible.
• Biopsy IS absolutely contraindicated, since penetrating the globe seeds tumour into the orbit and converts a curable intraocular disease into a lethal extraocular one. The diagnosis is made clinically and radiologically