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

Helen Hanson; Miranda Durkie; Fiona Lalloo; Louise Izatt; Terri P. McVeigh; Jackie A. Cook; Carole Brewer; James Drummond; Treena Cranston; Samantha Butler; Ruth Casey; Tricia Tan; Daniel Morganstein; Diana M. Eccles; Marc Tischkowitz; Clare Turnbull; Emma Roisin Woodward; Eamonn R. Maher

doi:10.1136/jmedgenet-2021-108355

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

Helen Hanson
, Miranda Durkie
, Fiona Lalloo
, Louise Izatt
, Terri P. McVeigh
, Jackie A. Cook
, Carole Brewer
, James Drummond
, Treena Cranston
, Samantha Butler
, Ruth Casey
, Tricia Tan
, Daniel Morganstein
, Diana M. Eccles
, Marc Tischkowitz
, Clare Turnbull
, Emma Roisin Woodward
, Eamonn R. Maher

St George's University Hospitals NHS Foundation Trust
Sheffield Diagnostic Genetics Service
Central Manchester University Hospitals NHS Foundation Trust
Comenius University
University of Edinburgh
Cambridge University Hospital Foundation Trust
Churchill Hospital
Cambridge University Hospitals NHS Foundation Trust
Imperial College London
Royal Marsden Hospital NHS Trust
University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
University of Southampton
Manchester University NHS Foundation Trust
St Mary's Hospital, Stannington
University College Birmingham
Birmingham Women's NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

21 Citations (SciVal)

108 Downloads (Pure)

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.

Original language	English
Pages (from-to)	107-111
Number of pages	5
Journal	Journal of Medical Genetics
Volume	60
Issue number	2
Early online date	8 Mar 2022
DOIs	https://doi.org/10.1136/jmedgenet-2021-108355
Publication status	Published - 24 Jan 2023

Bibliographical note

Funding

HH and FL are supported by Cancer Research CRUK Catalyst Award, CanGene-CanVar (C61296/A27223). RC is supported by GIST Support UK. ERW is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). ERM thanks the NIHR Cambridge Biomedical Research Centre for support. The University of Cambridge has received salary support (ERM) from the NHS in the East of England through the Clinical Academic Reserve.

Funders	Funder number
Cancer Research CRUK	C61296/A27223
GIST Support UK
Manchester Biomedical Research Centre	IS-BRC-1215-20007
National Institute for Health and Care Research

Keywords

Humans
Genetic Testing
Paraganglioma/genetics
Pheochromocytoma/genetics
Germ-Line Mutation/genetics
Adrenal Gland Neoplasms/genetics
United Kingdom
Genetic Predisposition to Disease
Electron Transport Complex II/genetics

Access to Document

10.1136/jmedgenet-2021-108355

H Hanson et al_UK recommendations for SDHA germline genetic testing and surveillance in clinical practice
Copyright © Author(s) (or their employer(s)), 2023. Re-use permitted under CC BY. Published by BMJ.
Final published version, 364 KBLicence: CC BY 4.0

Cite this

Hanson, H., Durkie, M., Lalloo, F., Izatt, L., McVeigh, T. P., Cook, J. A., Brewer, C., Drummond, J., Cranston, T., Butler, S., Casey, R., Tan, T., Morganstein, D., Eccles, D. M., Tischkowitz, M., Turnbull, C., Woodward, E. R., & Maher, E. R. (2023). UK recommendations for SDHA germline genetic testing and surveillance in clinical practice. Journal of Medical Genetics, 60(2), 107-111. https://doi.org/10.1136/jmedgenet-2021-108355

@article{c967b8e6568947a7b3e0a9775aa1b2c5,

title = "UK recommendations for SDHA germline genetic testing and surveillance in clinical practice",

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.",

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author = "Helen Hanson and Miranda Durkie and Fiona Lalloo and Louise Izatt and McVeigh, \{Terri P.\} and Cook, \{Jackie A.\} and Carole Brewer and James Drummond and Treena Cranston and Samantha Butler and Ruth Casey and Tricia Tan and Daniel Morganstein and Eccles, \{Diana M.\} and Marc Tischkowitz and Clare Turnbull and Woodward, \{Emma Roisin\} and Maher, \{Eamonn R.\}",

note = "Copyright {\textcopyright} Author(s) (or their employer(s)), 2023. Re-use permitted under CC BY. Published by BMJ.",

year = "2023",

month = jan,

day = "24",

doi = "10.1136/jmedgenet-2021-108355",

language = "English",

volume = "60",

pages = "107--111",

journal = "Journal of Medical Genetics",

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Hanson, H, Durkie, M, Lalloo, F, Izatt, L, McVeigh, TP, Cook, JA, Brewer, C, Drummond, J, Cranston, T, Butler, S, Casey, R, Tan, T, Morganstein, D, Eccles, DM, Tischkowitz, M, Turnbull, C, Woodward, ER & Maher, ER 2023, 'UK recommendations for SDHA germline genetic testing and surveillance in clinical practice', Journal of Medical Genetics, vol. 60, no. 2, pp. 107-111. https://doi.org/10.1136/jmedgenet-2021-108355

TY - JOUR

T1 - UK recommendations for SDHA germline genetic testing and surveillance in clinical practice

AU - Hanson, Helen

AU - Durkie, Miranda

AU - Lalloo, Fiona

AU - Izatt, Louise

AU - McVeigh, Terri P.

AU - Cook, Jackie A.

AU - Brewer, Carole

AU - Drummond, James

AU - Cranston, Treena

AU - Butler, Samantha

AU - Casey, Ruth

AU - Tan, Tricia

AU - Morganstein, Daniel

AU - Eccles, Diana M.

AU - Tischkowitz, Marc

AU - Turnbull, Clare

AU - Woodward, Emma Roisin

AU - Maher, Eamonn R.

PY - 2023/1/24

Y1 - 2023/1/24

N2 - 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.

AB - 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.

KW - Humans

KW - Genetic Testing

KW - Paraganglioma/genetics

KW - Pheochromocytoma/genetics

KW - Germ-Line Mutation/genetics

KW - Adrenal Gland Neoplasms/genetics

KW - United Kingdom

KW - Genetic Predisposition to Disease

KW - Electron Transport Complex II/genetics

UR - https://www.scopus.com/pages/publications/85131106728

UR - https://jmg.bmj.com/content/60/2/107

U2 - 10.1136/jmedgenet-2021-108355

DO - 10.1136/jmedgenet-2021-108355

M3 - Article

C2 - 35260474

SN - 0022-2593

VL - 60

SP - 107

EP - 111

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 2

ER -

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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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