SDHC phaeochromocytoma and paraganglioma: A UK-wide case series
Sophie T. Williams
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Search for more papers by this authorProdromos Chatzikyriakou
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Search for more papers by this authorPaul V. Carroll
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorBarbara M. McGowan
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorAnand Velusamy
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorGemma White
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorRupert Obholzer
Department of Ear, Nose, Throat Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorScott Akker
Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorNicola Tufton
Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorRuth T. Casey
Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Department of Medical Genetics, University of Cambridge, Cambridge, UK
Search for more papers by this authorEamonn R. Maher
Department of Medical Genetics, University of Cambridge, Cambridge, UK
Search for more papers by this authorSoo-Mi Park
Department of Clinical Genetics, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorMary Porteous
South East Scotland Genetic Service, Western General Hospital, Edinburgh, Scotland, UK
Search for more papers by this authorRebecca Dyer
South East Scotland Genetic Service, Western General Hospital, Edinburgh, Scotland, UK
Search for more papers by this authorTricia Tan
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Search for more papers by this authorFlorian Wernig
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Search for more papers by this authorAngela F. Brady
North West Thames Regional Genetics Service, Northwick Park Hospital, London, UK
Search for more papers by this authorMonika Kosicka-Slawinska
North West Thames Regional Genetics Service, Northwick Park Hospital, London, UK
Search for more papers by this authorBenjamin C. Whitelaw
Department of Endocrinology, King's College Hospital, London, UK
Search for more papers by this authorHuw Dorkins
Department of Clinical Genetics, Leicester Royal Infirmary, Leicester, UK
Search for more papers by this authorFiona Lalloo
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester, UK
Search for more papers by this authorPaul Brennan
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorJoseph Carlow
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorRichard Martin
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorAnna L. Mitchell
Department of Endocrinology, Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle, UK
Search for more papers by this authorRachel Harrison
Department of Clinical Genetics, Nottingham University Hospitals NHS Trust, Nottingham, UK
Search for more papers by this authorLara Hawkes
Department of Clinical Genetics, Churchill Hospital, Oxford, UK
Search for more papers by this authorJohn Newell-Price
Department of Oncology and Metabolism, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Search for more papers by this authorAlan Kelsall
Department of Oncology and Metabolism, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Search for more papers by this authorRebecca Igbokwe
Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, UK
Search for more papers by this authorJulian Adlard
Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
Search for more papers by this authorSchaida Schirwani
Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
Search for more papers by this authorRosemarie Davidson
Department of Clinical Genetics, Queen Elizabeth University Hospital, Glasgow, Scotland, UK
Search for more papers by this authorPatrick J. Morrison
Department of Medical Genetics, Belfast City Hospital, Belfast, Northern Ireland, UK
Search for more papers by this authorTeng-Teng Chung
Department of Endocrinology, University College London Hospital NHS Foundation Trust, London, UK
Search for more papers by this authorChristopher Bowles
Exeter Genomics Laboratory, Royal Devon and Exeter Hospital, Exeter, UK
Search for more papers by this authorCorresponding Author
Louise Izatt
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
Correspondence Louise Izatt, Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Email: [email protected]
Search for more papers by this authorSophie T. Williams
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Search for more papers by this authorProdromos Chatzikyriakou
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Search for more papers by this authorPaul V. Carroll
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorBarbara M. McGowan
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorAnand Velusamy
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorGemma White
Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorRupert Obholzer
Department of Ear, Nose, Throat Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
Search for more papers by this authorScott Akker
Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorNicola Tufton
Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorRuth T. Casey
Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Department of Medical Genetics, University of Cambridge, Cambridge, UK
Search for more papers by this authorEamonn R. Maher
Department of Medical Genetics, University of Cambridge, Cambridge, UK
Search for more papers by this authorSoo-Mi Park
Department of Clinical Genetics, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
Search for more papers by this authorMary Porteous
South East Scotland Genetic Service, Western General Hospital, Edinburgh, Scotland, UK
Search for more papers by this authorRebecca Dyer
South East Scotland Genetic Service, Western General Hospital, Edinburgh, Scotland, UK
Search for more papers by this authorTricia Tan
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Search for more papers by this authorFlorian Wernig
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Search for more papers by this authorAngela F. Brady
North West Thames Regional Genetics Service, Northwick Park Hospital, London, UK
Search for more papers by this authorMonika Kosicka-Slawinska
North West Thames Regional Genetics Service, Northwick Park Hospital, London, UK
Search for more papers by this authorBenjamin C. Whitelaw
Department of Endocrinology, King's College Hospital, London, UK
Search for more papers by this authorHuw Dorkins
Department of Clinical Genetics, Leicester Royal Infirmary, Leicester, UK
Search for more papers by this authorFiona Lalloo
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester, UK
Search for more papers by this authorPaul Brennan
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorJoseph Carlow
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorRichard Martin
Northern Genetics Service, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK
Search for more papers by this authorAnna L. Mitchell
Department of Endocrinology, Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle, UK
Search for more papers by this authorRachel Harrison
Department of Clinical Genetics, Nottingham University Hospitals NHS Trust, Nottingham, UK
Search for more papers by this authorLara Hawkes
Department of Clinical Genetics, Churchill Hospital, Oxford, UK
Search for more papers by this authorJohn Newell-Price
Department of Oncology and Metabolism, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Search for more papers by this authorAlan Kelsall
Department of Oncology and Metabolism, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Search for more papers by this authorRebecca Igbokwe
Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, UK
Search for more papers by this authorJulian Adlard
Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
Search for more papers by this authorSchaida Schirwani
Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
Search for more papers by this authorRosemarie Davidson
Department of Clinical Genetics, Queen Elizabeth University Hospital, Glasgow, Scotland, UK
Search for more papers by this authorPatrick J. Morrison
Department of Medical Genetics, Belfast City Hospital, Belfast, Northern Ireland, UK
Search for more papers by this authorTeng-Teng Chung
Department of Endocrinology, University College London Hospital NHS Foundation Trust, London, UK
Search for more papers by this authorChristopher Bowles
Exeter Genomics Laboratory, Royal Devon and Exeter Hospital, Exeter, UK
Search for more papers by this authorCorresponding Author
Louise Izatt
Department Medical Molecular Genetics, King's College London, Guy's Hospital, London, UK
Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
Correspondence Louise Izatt, Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Email: [email protected]
Search for more papers by this authorAbstract
Objective
Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported.
Design
This retrospective case series collated data from 18 UK Genetics and Endocrinology departments.
Patients
Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included.
Measurements
Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation.
Results
We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11–79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79–0.99) in probands, and 0.16 (CI: 0–0.31) in non-probands, respectively.
Conclusions
This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
| Filename | Description |
|---|---|
| cen14594-sup-0001-20210920_Figure_S1_BLAST_Human_Succinate_dehydrogenase_SDHC_D0VWV4_LEGEND.pdf210.7 KB | Supplementary Information. |
| cen14594-sup-0002-20210729_Figure_S2_Cumulative_tumour_risk_in_SDHC_LEGEND.pdf107.3 KB | Supplementary Information. |
| cen14594-sup-0003-20210729_Supplementary_Table_1_Patients_with_multiple_SDHC.pdf23.1 KB | Supplementary Information. |
| cen14594-sup-0004-20210729_Supplementary_Table_2_Tumours_in_Non_proband_SDHC_cases.pdf22.5 KB | Supplementary Information. |
| cen14594-sup-0005-20210729_Supplementary_Table_3_Clinical_characteristics_and_disease.pdf183.9 KB | Supplementary Information. |
| cen14594-sup-0006-20210920_Appendix_SDHC_phaeochromocytoma_and_paraganglioma_REF.pdf150.7 KB | Supplementary information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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