Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non‐syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma. (6th April 2013)

• Record Type: Journal Article
• Authors: Jafri, Mariam; Whitworth, James; Rattenberry, Eleanor; Vialard, Lindsey; Kilby, Gail; Kumar, Ajith V.; Izatt, Louise; Lalloo, Fiona; Brennan, Paul; Cook, Jackie; Morrison, Patrick J.; Canham, Natalie; Armstrong, Ruth; Brewer, Carole; Tomkins, Susan; Donaldson, Alan; Barwell, Julian; Cole, Trevor R.; Atkinson, A. Brew; Aylwin, Simon; Ball, Steve G.; Srirangalingam, Umasuthan; Chew, Shern L.; Evans, Dafydd Gareth R; Hodgson, Shirley V.; Irving, Richard; Woodward, Emma; Macdonald, Fiona; Maher, Eamonn R.
• Is Part Of: Clinical endocrinology. Volume 78:Number 6(2013:Jun.)
• Page Start: 898
• Page End: 906
• Publication Date: 2013-04-06
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12074
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12074-abs-0001"> <title>Summary</title> <sec id="cen12074-sec-0001" sec-type="section"> <title>Objectives</title> <p>Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated <italic>VHL</italic>, <italic>SDHB</italic> and <italic>SDHD</italic> mutation testing in cohorts of patients with non‐syndromic PPGL and head and neck paraganglioma (HNPGL).</p> </sec> <sec id="cen12074-sec-0002" sec-type="section"> <title>Design</title> <p>Prospective, observational evaluation of NHS practice.</p> </sec> <sec id="cen12074-sec-0003" sec-type="section"> <title>Patients</title> <p>Individuals with PPGL/HNPGL referred to a supraregional genetics testing service over a 10‐year period.</p> </sec> <sec id="cen12074-sec-0004" sec-type="section"> <title>Measurements</title> <p>Clinical (age, tumour site, malignancy, etc.), mutation frequencies and characteristics.</p> </sec> <sec id="cen12074-sec-0005" sec-type="section"> <title>Results</title> <p>A total of 501 probands with PPGL (<italic>n</italic> = 413) or HNPGL (<italic>n</italic> = 88) were studied. Thirty‐one percent of patients with PPGL presented had a pathogenic mutation in <italic>SDHB</italic>, <italic>SDHD</italic> or <italic>VHL</italic>. Mutation detection rates were highest in those with a positive family history (62%), malignancy (53%), multiple tumours (33%) or PGL (44%). Twenty‐eight percent of individuals with a single sporadic phaeochromocytoma had a mutation. Overall, 63% of patients with HNPGL had a mutation (92% of those with a family history, 89% of those with multicentric tumours and 34% of those with a single sporadic HNPGL). Penetrance was calculated in 121 <italic>SDHB</italic> mutation‐positive probands and 187 of their mutation‐positive relatives. Most relatives were asymptomatic and lifetime penetrance in non‐proband <italic>SDHB</italic> mutation carriers was <50%.</p> </sec> <sec id="cen12074-sec-0006" sec-type="section"> <title>Conclusions</title> <p>Practice‐based evaluations of genetic testing in PPGL reveal high mutation detection rates. Although clinical criteria can be used to prioritize mutation testing, mutations were detected in 'low risk groups' indicating a need for comprehensive and inexpensive genetic testing strategies for PPGL and HNPGL.</p> </sec> </abstract>