Dear Editor:

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors that arise from the adrenal medulla or from the extra-adrenal sympathetic and parasympathetic paraganglia respectively. Now we know that more than 30% of patients develop extra-adrenal tumors (Cascon et al. 2009b, Mannelli et al. 2009), the percentage of malignant cases depends on tumor location and/or genetic background (from ∼3% in RET- or VHL-related cases to 31% described for SDHB mutation carriers; Welander et al. 2011), and the probability of carrying a germline mutation in one of the PCC/PGL susceptibility genes is approaching 50%. Regarding the latter, up to four genes (SDHAF2, SDHA, TMEM127, and MAX) have recently been incorporated into the ‘catalog’ of PCC/PGL susceptibility genes (Hao et al. 2009, Burnichon et al. 2010, Qin et al. 2010, Comino-Mendez et al. 2011). Before the discovery of these genes, 30–40% of PCC/PGL cases were thought to be hereditary with autosomal inheritance caused by germline mutations affecting one of six major susceptibility genes: RET, VHL, SDHB, SDHC, SDHD, and NF1 (Cascon et al. 2009b, Mannelli et al. 2009). Recent international collaborations, focused on establishing the involvement of the novel identified genes, suggested that overall they could explain an additional 6% of the negative-tested patients (Bayley et al. 2010, Yao et al. 2010, Burnichon et al. 2012). In addition to this high and heterogeneous genetic predisposition, there is a unknown percentage of familial cases (i.e. with familial antecedents of PCC/PGL and/or with other clinical characteristics suggesting a hereditary disease) that do not harbor mutations in any of the susceptibility genes mentioned earlier.

Although PCCs/PGLs are infrequently diagnosed during childhood, it is possible to find pediatric …