Approximately 40% of the tumors of the autonomic nervous system, pheochromocytomas and paragangliomas (PCC/PGL), are associated with an underlying inherited mutation, more than any other tumor type. Thus, germline mutation testing is recommended for all patients with PCC/PGL. Strong evidence supports an association of susceptibility for PCC/PGL with germline mutations in 10 genes (FH, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, and VHL); mutations in an additional 5 genes also have been associated with disease susceptibility but with lower levels of evidence (EGLN1 [PHD2], EPAS1 [HIF2A], KIF1B, MET, and SDHAF2).¹ Even for genes in which an association between mutation and disease has been well established, the frequency of mutations is quite rare; thus, a paucity of data exist on which to base clinical recommendations for patients regarding the risk for developing the first PCC/PGL (eg, if they are identified though familial mutation testing), additional primary PCC/PGLs, metastatic disease, and other tumor types.

大约 40% 的自主神经系统肿瘤、嗜铬细胞瘤和副神经节瘤 (PCC/PGL) 与潜在的遗传突变相关，比任何其他肿瘤类型都多。因此，建议对所有 PCC/PGL 患者进行种系突变检测。强有力的证据支持 PCC/PGL 易感性与 10 个基因（FH、MAX、NF1、RET、SDHA、SDHB、SDHC、SDHD、TMEM127和VHL）中的种系突变相关；另外 5 个基因的突变也与疾病易感性有关，但证据水平较低（EGLN1 [PHD2]，EPAS1 [HIF2A]、KIF1B、MET和SDHAF2）。¹即使对于突变与疾病之间的关联已得到充分确定的基因，突变的频率也相当罕见；因此，缺乏数据可作为临床建议的基础，即患者出现第一个 PCC/PGL 的风险（例如，如果通过家族突变检测发现）、其他原发性 PCC/PGL、转移性疾病和其他肿瘤类型。