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. 2023 Feb;60(2):107-111.
doi: 10.1136/jmedgenet-2021-108355. Epub 2022 Mar 8.

UK recommendations for SDHA germline genetic testing and surveillance in clinical practice

Helen Hanson  1   2 , Miranda Durkie  3 , Fiona Lalloo  4 , Louise Izatt  5 , Terri P McVeigh  6 , Jackie A Cook  7 , Carole Brewer  8 , James Drummond  9 , Samantha Butler  10 , Treena Cranston  11 , Ruth Casey  12   13 , Tricia Tan  14 , Daniel Morganstein  15 , Diana M Eccles  16 , Marc Tischkowitz  13 , Clare Turnbull  2 , Emma Roisin Woodward  4   17 , Eamonn R Maher  13 ; UK Cancer Genetics Centres
Collaborators, Affiliations

UK recommendations for SDHA germline genetic testing and surveillance in clinical practice

Helen Hanson et al. J Med Genet. 2023 Feb.

Abstract

SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.

Keywords: endocrinology; genetic counselling; genetic predisposition to disease; genetic testing.

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Conflict of interest statement

Competing interests: RC has received speakers' honoraria from Novartis and Ipsen; DM has received speakers' honoraria from Roche and MSD and speakers' honoraria and consulting fees from Bristol Myers Squib.

References

    1. Boikos SA, Pappo AS, Killian JK, LaQuaglia MP, Weldon CB, George S, Trent JC, von Mehren M, Wright JA, Schiffman JD, Raygada M, Pacak K, Meltzer PS, Miettinen MM, Stratakis C, Janeway KA, Helman LJ. Molecular subtypes of KIT/PDGFRA wild-type gastrointestinal stromal tumors. JAMA Oncol 2016;2. 10.1001/jamaoncol.2016.0256 - DOI - PMC - PubMed
    1. Casey RT, Ascher DB, Rattenberry E, Izatt L, Andrews KA, Simpson HL, Challis B, Park S-M, Bulusu VR, Lalloo F, Pires DEV, West H, Clark GR, Smith PS, Whitworth J, Papathomas TG, Taniere P, Savisaar R, Hurst LD, Woodward ER, Maher ER. SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity. Mol Genet Genomic Med 2017;5:237–50. 10.1002/mgg3.279 - DOI - PMC - PubMed
    1. van der Tuin K, Mensenkamp AR, Tops CMJ, Corssmit EPM, Dinjens WN, van de Horst-Schrivers ANA, Jansen JC, de Jong MM, Kunst HPM, Kusters B, Leter EM, Morreau H, van Nesselrooij BMP, Oldenburg RA, Spruijt L, Hes FJ, Timmers HJLM,. Clinical aspects of SDHA-related pheochromocytoma and paraganglioma: a nationwide study. J Clin Endocrinol Metab 2018;103:438–45. 10.1210/jc.2017-01762 - DOI - PubMed
    1. Bausch B, Schiavi F, Ni Y, Welander J, Patocs A, Ngeow J, Wellner U, Malinoc A, Taschin E, Barbon G, Lanza V, Söderkvist P, Stenman A, Larsson C, Svahn F, Chen J-L, Marquard J, Fraenkel M, Walter MA, Peczkowska M, Prejbisz A, Jarzab B, Hasse-Lazar K, Petersenn S, Moeller LC, Meyer A, Reisch N, Trupka A, Brase C, Galiano M, Preuss SF, Kwok P, Lendvai N, Berisha G, Makay Özer, Boedeker CC, Weryha G, Racz K, Januszewicz A, Walz MK, Gimm O, Opocher G, Eng C, Neumann HPH, European-American-Asian Pheochromocytoma-Paraganglioma Registry Study Group . Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SdhA, TMEM127, Max, and SDHAF2 for gene-informed prevention. JAMA Oncol 2017;3:1204–12. 10.1001/jamaoncol.2017.0223 - DOI - PMC - PubMed
    1. Benn DE, Zhu Y, Andrews KA, Wilding M, Duncan EL, Dwight T, Tothill RW, Burgess J, Crook A, Gill AJ, Hicks RJ, Kim E, Luxford C, Marfan H, Richardson AL, Robinson B, Schlosberg A, Susman R, Tacon L, Trainer A, Tucker K, Maher ER, Field M, Clifton-Bligh RJ. Bayesian approach to determining penetrance of pathogenic SDH variants. J Med Genet 2018;55:729–34. 10.1136/jmedgenet-2018-105427 - DOI - PMC - PubMed

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