HN04 GENETICS OF HEAD AND NECK PARAGANGLIOMA

Paragangliomas (PGL) of the head and neck are rare tumours derived from neural crest origin that occur in both sporadic and hereditary forms. Genetic predisposition to paraganglioma affects up to 50% of all patients with head and neck paraganglioma. Patients with familial paraganglioma tend to present at a younger age and with multiple tumours. In the past, familial cases were attributed phenotypically to particular groupings, such as PGL type 1. Recent advances have identified mutations in genes encoding the three SDH subunits (SDHB, SDHC, SDHD) as responsible for the majority of familial head and neck paraganglioma. Succinate dehydrogenase is a mitochondrial enzyme complex with an important role in both the Kreb’s cycle and the mitochondrial electron transport chain. These mutations lead to the overexpression of several hypoxia‐inducible genes resulting in cellular proliferation and the development of paragangliomas. Understanding the relationship between mutations of SDHB, SHDC and SDHD and clinical manifestations of familial paraganglioma is important in the management, genetic testing and appropriate genetic counselling of individuals.