Retinoblastoma is the most common intraocular malignancy in children and is the prototype inherited cancer predisposition syndrome. About 60% of new patients exhibit unilateral ocular involvement with familial inheritance pattern. The remaining patients have a heritable form of retinoblastoma, which is often associated with bilateral ocular involvement, germline transmission to offspring, and second primary tumors.^[1] In most retinoblastoma families, the penetrance (the proportion of individuals with a germline mutation in the RB gene who develop clinical manifestations of the disease) is about 90%.^[2] However, about one in seven families will exhibit reduced penetrance as low as 30–60%. This chapter will focus on features that are specific to low-penetrance retinoblastoma (Box 49.1). The features of retinoblastoma in general are covered in  Chapter 48.

The diseased-eye ratio (DER), …