UK recommendations for SDHA germline genetic testing and surveillance in clinical practice. Issue 2 (8th March 2022)

• Record Type: Journal Article
• Authors: Hanson, Helen; Durkie, Miranda; Lalloo, Fiona; Izatt, Louise; McVeigh, Terri P; Cook, Jackie A; Brewer, Carole; Drummond, James; Butler, Samantha; Cranston, Treena; Casey, Ruth; Tan, Tricia; Morganstein, Daniel; Eccles, Diana M; Tischkowitz, Marc; Turnbull, Clare; Woodward, Emma Roisin; Maher, Eamonn R
• Other Names: author non-byline.; Donaldson Alan author non-byline.; Pelz Frauke author non-byline.; George Angela author non-byline.; Kulkarni Anju author non-byline.; Halliday Dorothy author non-byline.; Snape Katie author non-byline.; Ong Kai-Ren author non-byline.; Harrison Rachel author non-byline.; Adlard Julian author non-byline.; Greenhalgh Lynn author non-byline.; Murray Jennie author non-byline.; Kumar Ajith author non-byline.; Martin Richard author non-byline.; Goudie David author non-byline.; Davison Rosemarie author non-byline.; Rea Gillian author non-byline.; Miedzybrodzka Zosia author non-byline.; Barwell Julian author non-byline.; Side Lucy author non-byline.
• Is Part Of: Journal of medical genetics. Volume 60:Issue 2(2023)
• Page Start: 107
• Page End: 111
• Publication Date: 2022-03-08
• Subjects: endocrinology -- genetic counselling -- genetic predisposition to disease -- genetic testing; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2021-108355
• Languages: English
• ISSNs: 1468-6244

Abstract

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.