Hereditary paraganglioma target's diverse paraganglia

Paragangliomas are highly vascularised and often heritable tumours derived from paraganglia, a diffuse neuroendocrine system dispersed from skull base to the pelvic floor. The carotid body, a small oxygen sensing organ located at the bifurcation of the carotid artery in the head and neck and the adrenal medulla in the abdomen, are the most common tumour sites. It now appears that mutations in SDHB, SDHC, and SDHD, which encode subunits of mitochondrial complex 11 (succinate dehydrogenase; succinate-ubiquinone oxidoreductase), are responsible for the majority of familial paragangliomas and also for a significant fraction of non-familial tumours. Germline mutations in complex 11 genes are associated with the development of paragangliomas in diverse anatomical locations, including phaeochromocytomas, a finding that has important implications for the clinical management of patients and genetic counselling of families. Consequently, patients with a paraganglioma tumour, including phaeochromocytoma, and a complex 11 germline mutation should be diagnosed with hereditary paraganglioma, regardless of family history, anatomical location, or multiplicity of tumours. This short review attempts to bring together relevant genetic data on paragangliomas with a particular emphasis on head and neck paragangliomas and phaeochromocytomas.