Phaeochromocytoma, new genes and screening strategies

Summary Following recent advances in the genetics of phaeochromocytomas and paragangliomas, the members of the European Network for the Study of Adrenal Tumours (ENS@T) Phaeochromocytoma Working Group have decided to share their genotyping data and to propose European recommendations for phaeochromocytoma/functional paraganglioma (PH/FPGL) genetic testing. Germline DNA from 642 patients was analysed by ENS@T teams. In 166 patients (25·9%) the disease was familial and caused by germline mutations in VHL (56), SDHB (34), SDHD (31), RET (31) or NF1 (14), causing von Hippel‐Lindau disease, SDHB‐ or SDHD‐PH/FPGL syndromes, multiple endocrine neoplasia type 2 (MEN 2) and type 1 neurofibromatosis (NF1), respectively. In almost 60% of inherited cases it was possible to formulate a probable genetic diagnosis based on family history and/or typical syndromic presentation. Genetic testing revealed mutations in 12·7% of cases with an apparently sporadic presentation. Several clinical characteristics, such as young age at onset, the presence of bilateral, extra‐adrenal or multiple tumours or a malignant tumour, should be seen as indications for genetic testing. The ENS@T Phaeochromocytoma Working Group recommends the genetic testing of all patients with PH and FPGL and suggests a practice algorithm for the management of their exploration.