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Genetic Testing in Pheochromocytoma or Functional Paraganglioma

From the Université Paris-Descartes, Faculté de Médecine; Département de Génétique and Unité d’Hypertension Artérielle, Hôpital Européen Georges Pompidou, and Service des Maladies Endocrininiennes et Mètaboliques, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris; L’Institut National de la Santé et de la Recherche Médicale (INSERM) U36, Collège de France; INSERM U567; Centre National de la Recherche Scientifique Unitè Mixte de Recherche 8104, Institut Cochin; Service de Cancérologie Endocrinienne and Service de Génétique, Institut Gustave Roussy, Villejuif, France; Service de Mèdecine Interne et Endocrinologie Hôpital Henri Mondor, Créteil, France; Unité d’Endocrinologie, Centre Hospitalier Universitaire (CHU) and INSERM Equipe Mixte 0105 Grenoble, France; Service de Medecine Interne et Hypertension Artérielle, CHU Rangueil; INSERM U558, 31059 Toulouse, France; Service d’Endocrinologie, CHU de Reims, Reims; Laboratoire de Génétique, Hôpital Edouard Herriot, Lyon; Service d’Endocrinologie, Hôpital de l’Hôtel-Dieu, CHU de Nantes, Nantes; Service d’Endocrinologie, CHU de Marseille, Marseille; Génétique Oncologique Ecole Pratique des Hautes Etudes-Unitè Mixte de Recherche 8125, Faculté de Médecine Paris-Sud; Service d’Urologie, Hôpital de Bicêtre, Le Kremlin-Bicêtre; Service d’Endocrinologie, CHU d’Angers, Angers; and Service d’Endocrinologie, Hôpital de l’Archet, CHU de Nice, Nice, France

Address reprint requests to Anne-Paule Gimenez-Roqueplo, MD, PhD, Département de Génétique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75015 Paris, France; e-mail: anne-paule.gimenez{at}hop.egp.ap-hop-paris.fr

PURPOSE: To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl).

PATIENTS AND METHODS: We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria.

RESULTS: We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant.

CONCLUSION: Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.

Supported by the Cortico et Medullosurrenale: les Tumeurs Endocrines network, with the support of Projet Hospitalier de Recherche Clinique Grant No. AOM02068 and Grants from L’Institut National de la Santé et de la Recherche Médicale (INSERM) and the Ministère Délégué à la Recherche et aux Nouvelles Technologies; the Paraglioma network, with the support of Groupement d’Intèrêt Scientifique Institut des Maladies Rares; and Groupe des Tumeurs Endocrines, with the support of Ministère de la Santé et de la Protection Sociale. L.A. holds a fellowship from the Société Française d’Hypertension Artérielle, and A.-P.G.-R. holds a Contrat d’Interface pour Hospitaliers from INSERM.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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