Metastatic medulloblastoma in an adolescent with Simpson–Golabi–Behmel syndrome

Abstract

We describe the case of a 12-year-old Hispanic male with a clinical and molecular diagnosis of Simpson-Golabi-Behmel Syndrome (SGBS) who subsequently developed metastatic medulloblastoma. While individuals with SGBS have been documented to have increased risk for intra-abdominal tumors such as Wilms tumor and neuroblastoma, medulloblastomas, or CNS tumors in general, have not been reported in patients with this syndrome. Our patient was clinically diagnosed with SGBS as an infant. He presented with many of the common features of the syndrome, such as cleft palate, macroglossia, post-axial polydactyly, "coarse" facial features, and ventricular septal defects (VSDs). Molecular testing performed in April 2009 confirmed the SGBS diagnosis. This testing detected a large intragenic deletion in the GPC3 gene (more than 500 kb, 8 exons) extending from intron 2, 37 kb downstream of exon 2, to the 5' end of the gene, deleting exons 1 and 2. However, subsequent testing by gene-centric high-density array comparative genomic hybridization (aCGH) detected a deletion encompassing only exon 2. Therefore, the exact 5' boundary of the deletion cannot currently be determined, due to an apparent complex rearrangement upstream of exon 1. We present this case of metastatic medulloblastoma as a unique malignancy in a patient with SGBS.

Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

“…One case of medulloblastoma in SGBS has been reported (39). Currently, there do not appear to be specific genotype-phenotype correlations, and deletions and truncation mutations have been reported with and without tumor development.…”

“…Tumor screening similar to BWS screening has previously been used in these patients (40). Some have also suggested utilizing the β-HCG tumor marker due to previous reports of germ cell tumors in SGBS, however this is not a widespread recommendation (34,39). No screening recommendations have been made for CNS tumors in SGBS.…”

Metachronous Medulloblastoma in a Child With Successfully Treated Neuroblastoma: Case Report and Novel Findings of DNA Sequencing

“…Analyses of 9,432 long-term neuroblastoma survivors in 3 major studies indicated that 96 patients developed second cancers, including carcinomas, soft tissue sarcomas, glioblastomas, meningioma, melanomas, and hematologic malignancies, but none developed medulloblastoma (Table 3). [5][6][7] Neuroblastoma and, less commonly, medulloblastoma, have been reported in patients with cancer predisposition syn- [22][23][24] Our patient did not have clinical stigmata of these conditions and her genetic testing was negative for these syndromes.…”

Glypican4 promotes cardiac specification and differentiation by attenuating canonical Wnt and Bmp signaling

“…In vitro, the Wnt-promoting factor R-spondin 3 was shown to interact with Syndecans and Glypican3 (Ohkawara et al, 2011), suggesting a complex interaction of heparan sulphate proteoglycans and Wnt signaling components at the cell membrane. Interestingly, human SGBS patients have a tendency to develop pre-and postnatal tumors, such as Wilm's tumor, hepatoblastomas, neuroblastomas and gonadoblastomas (Golabi et al, 1993;Rodríguez-Criado et al, 2005;Thomas et al, 2012;Mateos et al, 2013). The development of these tumors has been brought into correlation with a misregulation of canonical Wnt signaling (Honecker et al, 2004;Lapunzina, 2005;Liu et al, 2008;Armengol et al, 2011), indicating that the lack of glypicans might result in a misregulation of canonical Wnt signaling in SGBS patients.…”