A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma.

The identification of 9 susceptibility genes for paraganglioma/ pheochromocytomabetween 2001and 2010 has led to the development of routine genetic tests. To study the evolution in genetic screeningfor paraganglioma/ pheochromocytomaover the past decade, we carried out a retrospective study on the tests performed in our laboratory from January 2001 to December 2010. A genetic testfor paraganglioma/ pheochromocytomawas assessed for 2 499 subjects, 1 620 index cases, and 879 presymptomatic familial genetic tests. A germline mutationin a PGL/PCC susceptibility gene was identified in 363 index cases(22.4%): 269 in SDHx genes (137 in SDHB, 100 in SDHD, 30 in SDHC , 2 in SDHA), 64 in VHL , 23 in RET , and 7 in TMEM127 . A presymptomatic paraganglioma/ pheochromocytomatest was positive in 427 subjects. Advances in molecular screening techniques led to an increase in the total number of mutation-carriers diagnosed each year. Overall, during the last decade, our laboratory identified a germline mutationin 44.7% of patients with a suspect hereditary PGL/PCC and in 8% of patients with an apparently sporadic PGL/PCC. During the past decade, the discoveries of new paraganglioma/ pheochromocytomasusceptibility genes and the subsequent progress of molecular screening techniques have enabled us to diagnose a hereditary paraganglioma/ pheochromocytomain about 22% of patients tested in routine practice. This genetic testingis of major importance for the follow-up of affected patients and for the genetic counsellingof their families.