Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.

Objective: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations.

Design: Retrospective case-series.

Patients: Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres.

Measurements: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.

Results: Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension.

Conclusion: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.