The paediatric patient with paraganglioma syndrome
Pheochromocytomas and paragangliomas (PCC/PGL) are rare tumours of the adrenal gland or derived from sympathetic and parasympathetic paraganglia occurring sporadically or as part of a familial cancer syndrome. Up to 20% of them are diagnosed in children, and they are not genetically well characterized. As most are functional tumors, children more often present with signs and symptoms related to hypertension. In fact, sustained hypertension is found in more than 6090% of paediatric pheochromocytoma cases, whereas it is reported in only 50% of adult cases.
Originally, it was suggested that 10% of PCCs are hereditary, but current advances in molecular genetics have shown that germline mutations occur in up to 3040% of PCC/PGLs. There are several features to take into account to suspect a hereditary tumor syndrome. Among them, the family history, the presence of multiple tumours or the age of onset are important clues to estimate the risk of a hereditary tumor syndrome. In this regards, 40% to 59% of PCCs patients younger than 18 years have germline mutations in some of the PCC/PGL susceptibility genes, and this proportion increases to 70% for those presenting before 10 years of age. According to data available, VHL is the most commonly (42%) mutated gene, followed by SDHB, SDHD, RET, and NF1. In some cases PCC/PGL presenting during childhood represents an early manifestation of an adult disease caused by predisposing germline mutations. Therefore, genetic testing should be performed in every child with PCC/PGL, because a proper characterization of the underlying mutation is a key factor in estimating the risk for development of malignant disease and contralateral tumour, which may also guide the follow-up and clinical management.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.