Pediatric paraganglioma: an early manifestation of an adult disease secondary to germline mutations.
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.


METHODS
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.


CONCLUSIONS
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.
Mora
Jaume
J
Laboratori de biologia molecular dels tumors del desenvolupament i Oncologia Pediàtrica, Hospital Sant Joan de Déu de Barcelona, Spain. jmora@hsjdbcn.org
Cascón
Alberto
A
Robledo
Mercedes
M
Catala
Albert
A
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012086:Reoperation; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed