Metastatic retinoblastoma: single institution experience over two decades.

BACKGROUND: Metastatic spread in retinoblastoma is a rare occurrence in developed countries but still associated with a poor prognosis. PATIENTS AND METHODS: Medical records of all metastatic retinoblastoma diagnosed during a 20-year period were retrospectively reviewed. RESULTS: Six patients out of 104 presented a metastatic disease with an incidence at diagnosis of 2%. Three had a metastatic disease at diagnosis, one patient a trilateral retinoblastoma and two a metastatic spread after enucleation. All but one were sporadic retinoblastoma. Central nervous system (CNS) involvement was reported in five patients, while one patient had an intraorbital lesion, and bone and bone marrow spread. Different treatment strategies were administered based on local treatment plus chemotherapy and radiotherapy with or without high-dose chemotherapy. An ifosfamide/carboplatin/etoposide regimen was administered in three patients resulting in a partial response. Out of six patients, four died, and two patients are alive at 60 and 63 months from diagnosis. Both children with a long follow-up were treated with high-dose chemotherapy. All but one of the patients with CNS involvement died; the survivor was a patient with pineal involvement. CONCLUSION: This retrospective review confirms a curable strategy based on local treatment and conventional plus high-dose chemotherapy. Patients with CNS involvement remain incurable.

Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at Exon 8 is associated with a highly variable phenotype.

BACKGROUND: Renal-coloboma syndrome (RCS) is an autosomal dominant disorder characterized by renal abnormalities and optic nerve defects, caused by heterozygous mutations of the PAX2 gene. This gene encodes for the PAX2 developmental nuclear transcription factor, which is primarily expressed during embryogenesis in kidneys, eyes, ears and in the central nervous system. The aim of the present study was to characterize PAX2 mutations in a renal coloboma syndrome family with a highly variable phenotype. METHODS: DNA screening was performed by direct sequencing. RESULTS: Five subjects over three generations presented with renal hypodysplasia or horseshoe kidneys in association with bilateral optic nerve colobomas in four cases, one patient with early-onset renal failure had no detectable eye defects. All five subjects carried a novel PAX2 mutation consisting in a frameshift mutation located in Exon 8 (G91 I del), which causes premature termination of translation and loss of the PAX2 transactivation domain. CONCLUSION: This is the first report of a PAX2 mutation located in Exon 8. The variability of clinical symptoms may be explained by the limited disruption of the protein sequence at the transactivation domain.