SDHB, SDHC, and SDHD Mutations in Head and Neck Paragangliomas

Head and neck paragangliomas (HNPs) are characterized by the development of benign, slow-growing, and highly vascularized tumors that derive from the neuroectoderm. The most common diseased state of HNPs is the neoplastic enlargement of their components. Most HNPs are hormonally silent and are clinically recognized by their anatomical pressure effects on adjacent structures. The carotid body is the major site, followed by the jugular, tympanic, and vagal paraganglia.

A positive family history is present in 10 to 50% of cases of HNP.

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 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.