Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas

Paraganglioma syndrome includes head and neck paraganglioma and pheochromocytoma, and is classified according to the three susceptibility genes involved, SDHB, SDHC, and SDHD. This study assessed the prevalence of germline mutations in SDHB, SDHC, and SDHD genes in a consecutive population admitted to Padova Hospital consisting of 20 patients with head and neck paraganglioma (HNP). Mutations were identified in the three genes in four affected individuals, three sporadic cases and one with family history of HNP. The novel SDHB p.R242C mutation was identified in a sporadic monolateral carotid body tumor. The SDHC p.Q147X mutation, the first to be described in Italy, was detected in a sporadic monolateral jugulotympanic paraganglioma. The SDHD p.Y114C mutation was identified in two unrelated patients, one familial case of bilateral carotid body tumor and one multiple paraganglioma. SDHB, SDHC, and SDHD molecular screening is important in all HNPs, with or without primary indicators of paraganglioma syndrome, to orient mutation-driven clinical screening for additional HNPs and pheochromocytoma.