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Review
. 2022 Jun 28;2(1):R65-R77.
doi: 10.1530/EO-22-0044. eCollection 2022 Jan.

Pheochromocytoma and paraganglioma: germline genetics and hereditary syndromes

Christie G Turin  1 , Molly M Crenshaw  2 , Lauren Fishbein  1   3
Affiliations
Review

Pheochromocytoma and paraganglioma: germline genetics and hereditary syndromes

Christie G Turin et al. Endocr Oncol. .

Abstract

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately 15-25% of PCC/PGL can become metastatic. Up to 30-40% of patients with PCC/PGL have a germline pathogenic variant in a known susceptibility gene for PCC/PGL; therefore, all patients with PCC/PGL should undergo clinical genetic testing. Most of the susceptibility genes are associated with variable penetrance for PCC/PGL and are associated with different syndromes, which include susceptibility for other tumors and conditions. The objective of this review is to provide an overview of the germline susceptibility genes for PCC/PGL, the associated clinical syndromes, and recommended surveillance.

Keywords: hereditary genetics; hereditary syndromes; paraganglioma; pheochromocytoma.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Figures

Figure 1
Figure 1
Germline PCC/PGL susceptibility gene cellular pathways.
See this image and copyright information in PMC

References

    1. Al-Sharefi A, Javaid U, Perros P, Ealing J, Truran P, Nag S, Kamaruddin S, Abouglila K, Cains F, Lewis L, et al.2019Clinical presentation and outcomes of phaeochromocytomas/paragangliomas in neurofibromatosis Type 1. European Endocrinology 1595–100. (10.17925/EE.2019.15.2.95) - DOI - PMC - PubMed
    1. Amar L, Pacak K, Steichen O, Akker SA, Aylwin SJB, Baudin E, Buffet A, Burnichon N, Clifton-Bligh RJ, Dahia PLM, et al.2021International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nature Reviews: Endocrinology 17435–444. (10.1038/s41574-021-00492-3) - DOI - PMC - PubMed
    1. Anderson Jr GH, Blakeman N, Streeten DH.1994The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. Journal of Hypertension 12609–615. (10.1097/00004872-199405000-00015) - DOI - PubMed
    1. Andrews KA, Ascher DB, Pires DEV, Barnes DR, Vialard L, Casey RT, Bradshaw N, Adlard J, Aylwin S, Brennan P, et al.2018Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. Journal of Medical Genetics 55384–394. (10.1136/jmedgenet-2017-105127) - DOI - PMC - PubMed
    1. Armaiz-Pena G, Flores SK, Cheng ZM, Zhang X, Esquivel E, Poullard N, Vaidyanathan A, Liu Q, Michalek J, Santillan-Gomez AA, et al.2021Genotype-phenotype features of germline variants of the TMEM127 pheochromocytoma susceptibility gene: a 10-year update. Journal of Clinical Endocrinology and Metabolism 106e350–e364. (10.1210/clinem/dgaa741) - DOI - PMC - PubMed

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