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Pediatric paraganglioma: An early manifestation of an adult disease secondary to germline mutations
Author(s) -
Mora Jaume,
Cascón Alberto,
Robledo Mercedes,
Catala Albert
Publication year - 2006
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20680
Subject(s) - germline mutation , men1 , medicine , germline , neurofibromatosis , sdhb , paraganglioma , multiple endocrine neoplasia , multiple endocrine neoplasia type 2 , pheochromocytoma , disease , germline mosaicism , mutation , endocrine system , oncology , genetics , pathology , gene , biology , hormone
Background Paraganglioma (PGL) and phaeochromocytoma (PCC) are chemotherapy and radiation‐resistant neuroendocrine tumors that arise from sympathetic tissue, and rarely occur in children. PCC may be associated with predisposing (germline) conditions like the multiple endocrine neoplasia type 2 (MEN2; OMIM 164761), von Hippel‐Lindau syndrome (VHL; OMIM 193300), and rarely neurofibromatosis type 1 syndrome (NF1; OMIM 162200) and multiple endocrine neoplasia type 1 (MEN1; OMIM 131100). PGL, on the other hand, may be related to predisposing germline conditions like the familial PGL syndrome and the NF1 syndrome. In adult studies, one of the highest predisposing factors for germline mutation among patients presenting apparently sporadic PCC/PGL was their age at presentation. The aim of this study was to determine the rate of germline mutations among the rare patients presenting with sporadic PGL during childhood. Procedure In this study, we report the genetic analysis for predisposing conditions for the only three PGL cases retrospectively identified at our pediatric institution in the last 20 years. Results None had NF1 clinical associated lesions. Mutation screening of genes associated to VHL ( VHL) , MEN ( RET) , and familial PGL ( SDH‐B, ‐C, and ‐D) showed that all cases had germline deletions in the SDHB gene. We report a novel mutation, c.778 del C. Importantly, several non‐symptomatic relatives were found to be carriers, thus ensuring them a clinical follow‐up. Conclusion According to our findings, PGL presenting during childhood represents an early manifestation of an adult disease caused by predisposing germline mutations. These results underline the importance of genetic studies in pediatric PGLs. Pediatric Blood Cancer 2006;47:785–789. © 2005 Wiley‐Liss, Inc.