Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect.

Patients with hereditary cancer are usually diagnosed earlier than patients with non-hereditary tumours. In children with isolated unilateral retinoblastoma, some of whom have a hereditary predisposition, this rule has been subject to debate. We have analysed the clinical manifestation of disease in 188 children with completely resolved mutational status. In 24 (13%) of these patients, testing of blood DNA showed a constitutional RB1 mutation. The distribution of age at diagnosis was not different between patients with and without a constitutional mutation. However, patients with loss of the maternally inherited RB1 allele had an earlier age at diagnosis than patients with loss of the paternally inherited RB1 allele. Our data show that early age at diagnosis does not identify patients with isolated unilateral retinoblastoma that have a higher risk of being carriers of a RB1 gene mutation. Our findings suggest that, at least in some patients, age at diagnosis is modified by a parent-of-origin effect.