Risk assessment of maternally inherited SDHD paraganglioma and phaeochromocytoma

• Published in: Journal of medical genetics Vol. 54; no. 2; pp. 125 - 133
• Main Authors: Burnichon, Nelly, Mazzella, Jean-Michaël, Drui, Delphine, Amar, Laurence, Bertherat, Jérôme, Coupier, Isabelle, Delemer, Brigitte, Guilhem, Isabelle, Herman, Philippe, Kerlan, Véronique, Tabarin, Antoine, Wion, Nelly, Lahlou-Laforet, Khadija, Favier, Judith, Gimenez-Roqueplo, Anne-Paule
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.02.2017; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adolescent; Adrenal disorders; Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - pathology; Adult; Cancer genetics; Cancer: endocrine; Chromosomes, Human, Pair 11 - genetics; Endocrinology and metabolism; Female; Genes; Genetic screening/counselling; Genetic Testing; Genetics; Germ-Line Mutation - genetics; Heterozygote; Human health and pathology; Humans; Life Sciences; Loss of Heterozygosity - genetics; Maternal Inheritance - genetics; Molecular genetics; Mutation; Paraganglioma - genetics; Paraganglioma - pathology; Patients; Pedigree; Pheochromocytoma - genetics; Pheochromocytoma - pathology; Risk Assessment; Succinate Dehydrogenase - genetics; Tumors; Genetics; Cancer: endocrine; Molecular genetics; Adrenal disorders; Genetic screening/counselling
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmedgenet-2016-104297

BackgroundGermline 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.ObjectiveTo assess the risk of PPGL occurrence on maternal transmission of SDHD mutation.MethodsPedigrees 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.ResultsA 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.ConclusionsThis 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.