American Journal of Medical Genetics 124A:397–401 (2004) Clinical Report Retinoblastoma, Pinealoma, and Mild Overgrowth in a Boy With a Deletion of RB1 and Neighbor Genes on Chromosome 13q14 Cristina Skrypnyk 1,2 and Oliver Bartsch 1 * 1 Institute of Clinical Genetics, Dresden University of Technology, Dresden, Germany 2 Department of Genetics, University of Oradea, Oradea, Romania We report on a 10-year-old boy with a normal karyotype and a chromosome 13q14 deletion of the retinoblastoma gene (RB1) by fluor- escence in situ hybridization (FISH). He showed subtle signs of overgrowth, includ- ing macrocephaly, hepatomegaly, and ingu- inal hernia. The boy also had cryptorchism and mild developmental delay. In his first months of life, variant Wiedemann–Beckwith syndrome was tentatively suspected and he was included in a careful tumor prevention program. At the age of 11 months, bifocal retinoblastoma of the left eye was diagnos- ed. Pinealoma was suspected at the age of 19 months and was removed by neurosur- gery at the age of 29 months. At 4 years and 4 months, the deletion of the RB1 gene was suspected on clinical grounds and was diag- nosed by FISH and molecular studies. At that time, he was a near-normal healthy playful kindergarten child, height 107 cm (0.3 SD), OFC 52.5 cm (þ0.8 SD), developmental age 3 – 3.5 years. The combination of retinoblas- toma, pinealoma, and deletion of the RB1 gene diagnosed by FISH has not been re- ported previously. The deletion spans at least 370–420 kb in size and is predicted to include proximal and distal neighbor genes. This report may assist in establishing the clinical signs of the contiguous gene syn- drome at the RB1 locus on 13q14. ß 2003 Wiley-Liss, Inc. KEY WORDS: retinoblastoma; pinealoma; RB1; chromosome 13q14; contiguous gene syndrome INTRODUCTION Retinoblastoma (RB; MIM *180200), the most fre- quent eye tumor of infancy and early childhood (1 in 12,000 children), is among the best understood of human diseases and results from mutations deleting or inacti- vating both alleles of the RB1 tumor-suppressor gene on chromosome 13q14 (Knudson’s two-hit model of carci- nogenesis in familial cancer syndromes) [Naumova and Sapienza, 1994]. The RB1 protein is in the control of the cell cycle and down-regulates the E2F transcription factor. About 40% of RB patients have a germline RB1 mutation, and therefore a high risk (penetrance about 90%) for bilateral or multifocal retinoblastoma, and a small but substantial risk for other tumors including pinealoma and osteosarcoma. The association of bilat- eral RB with pinealoma or another midline intracranial neoplasm has been named trilateral retinoblastoma [Bader et al., 1982], and was reported in approximately 5% of patients [De Potter et al., 1994]. The proportions of mutation types in hereditary RB are well known, com- prising 68% patients with a molecular mutation, 10% with a gross sized molecular deletion, and 5% with a deletion of the entire RB1 gene [Kloss et al., 1991; Dryja et al., 1993; Lohmann et al., 1996]. At the genomic DNA level, seven gross deletions of RB1 have been described [human gene mutation database], including one deletion of the entire RB1 gene [Dryja et al., 1993] and six deletions spanning one or two exons of RB1 [Kato et al., 1994; Bremner et al., 1997; Zayaczek et al., 1998, 1999]. We report on clinical, FISH, and molecular findings in a 10-year-old boy with retinoblastoma, pinealoma, mild MCA/MR syndrome, and a germline RB1 deletion diag- nosed by FISH. The combination has not been reported previously. Grant sponsor: The Saxonian Minister of Science and Culture for the support of CS; Grant number: 4.7531.50-04-0370-02/8. *Correspondence to: Dr. Oliver Bartsch, Institut fu ¨ r Klinische Genetik, Technische Universita ¨ t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. E-mail: obartsch@rcs.urz.tu-dresden.de Received 12 June 2002; Accepted 2 June 2003 DOI 10.1002/ajmg.a.20410 ß 2003 Wiley-Liss, Inc.