title: Risk assessment of maternally inherited SDHD paraganglioma and phaeochromocytoma.
abstract: Germline mutations in the SDHD tumour suppressor gene (11q23.1) predispose to phaeochromocytomas and paragangliomas (PPGL) mainly on a paternal transmission. However, PPGL have been recently reported in three carriers of a maternally inherited SDHD mutation.
  
  
  
  To assess the risk of PPGL occurrence on maternal transmission of SDHD mutation.
  
  
  
  Pedigrees of 80 SDHD-related families have been reviewed. 35 asymptomatic subjects carrying a maternally transmitted SDHD mutation were identified. 20 of them accepted to benefit from a PPGL imaging screening.
  
  
  
  A unique histologically proven biochemically negative phaeochromocytoma has been diagnosed in a 35-year-old woman. Molecular investigations carried out on tumour tissue revealed that the loss of heterozygosity encompassed the paternally derived q arm and the maternally derived p arm of chromosome 11.
  
  
  
  This study demonstrates that the risk of developing PPGL for a subject carrying a germline SDHD mutation on the maternal allele remains a rare scenario but does exist. Our data suggest an adjustment of current genetic counselling and clinical care recommendations for at-risk subjects. A targeted familial genetic test should be proposed from the age of 18 years to every subject having a mother carrying a germline SDHD mutation and a first medical workup, including imaging, should be recommended to SDHD-positive mutation carriers.
authors.affiliation: Service de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.|Faculté de Médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.|INSERM, UMR970, Paris-Centre de Recherche Cardiovasculaire, Paris, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.affiliation: Service de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Jean-Michaël
authors.initials: JM
authors.lastname: Mazzella
authors.affiliation: Service d'Endocrinologie, Centre Hospitalier Universitaire de Nantes, Hôpital Nord Laënnec, Nantes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Drui
authors.affiliation: Faculté de Médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.|INSERM, UMR970, Paris-Centre de Recherche Cardiovasculaire, Paris, France.|Unité d'Hypertension artérielle, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.affiliation: Faculté de Médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service d'Endocrinologie "Centre de référence maladies rares de la surrénale", Paris, France.|Centre Expert National COMETE-Cancer de la surrénale, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: Service de Génétique Médicale, unité d'Oncogénétique, Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.affiliation: Centre Hospitalier Universitaire de Reims, Département d'Endocrinologie, Diabétologie et Nutrition, Reims, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Delemer
authors.affiliation: Service d'Endocrinologie-Diabétologie-Nutrition, Centre Hospitalier Universitaire de Rennes, Hôpital Sud, Rennes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guilhem
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Département d'Oto-rhino-laryngologie et de Chirurgie de la tête et du cou, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Herman
authors.affiliation: Service d'Endocrinologie-Diabétologie-Nutrition, Centre Hospitalier Universitaire de Brest, Hôpital de la Cavale Blanche, Brest, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Kerlan
authors.affiliation: Département d'Endocrinologie, Centre Hospitalier Universitaire de Bordeaux, Hôpital de Haut-Lévêque, Pessac, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
authors.affiliation: Centre Hospitalier Universitaire de Grenoble, Hôpital Nord, Service d'Endocrinologie-Diabétologie-Nutrition, Grenoble, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Wion
authors.affiliation: Service de Psychiatrie de l'Adulte et du Sujet Agé, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité de Psychiatrie de Liaison, Paris, France.
authors.forename: Khadija
authors.initials: K
authors.lastname: Lahlou-Laforet
authors.affiliation: Faculté de Médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.|INSERM, UMR970, Paris-Centre de Recherche Cardiovasculaire, Paris, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Favier
authors.affiliation: Service de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.|Faculté de Médecine, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.|INSERM, UMR970, Paris-Centre de Recherche Cardiovasculaire, Paris, France.|Centre Expert National COMETE-Cancer de la surrénale, Paris, France.
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D000072741:Maternal Inheritance / Q000235:genetics; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase
keywords: Adrenal disorders; Cancer: endocrine; Genetic screening/counselling; Genetics; Molecular genetics