Familial paraganglioma syndromes

Paragangliomas and phaeochromocytomas may occur in syndromic or sporadic forms. The former are well recognised with multiple endocrine neoplasia (MEN) type 2 and von Hippel-Lindau syndromes. A few cases are associated with neurofibromatosis type 1. The familial paraganglioma-phaeochromocytoma syndromes are less well recognised, but as more genetic testing is performed, more cases belonging to this syndrome will be revealed. These syndromes result from mutations in one of three subunits of the succinate dehydrogenase (SDH) gene. There are four types: type 1 associated with SDHD, type 2 with an unknown gene, type 3 with SDHC and type 4 with SDHB. There are distinct genotypic-phenotypic correlations with each mutation. Patients with SDHB mutations have a positive family history in 33% of cases, present with single tumours around 30 years of age and have extra-adrenal paragangliomas mainly in the abdomen and pelvis; 20% may also have phaeochromocytomas, and tumours in these patients have a great propensity to metastasise. Patients with SDHD and SDHC mutations have a higher positive family history (66%) and have head and neck paragangliomas. SDHD patients present at 30 years with multiple tumours, while in SDHC mutation carriers, single tumours appear at around 38 years of age. A small percentage of patients with sporadic paragangliomas/phaeochromocytomas may have SDH mutations as well.