TY - JOUR
T1 - SDHC phaeochromocytoma and paraganglioma: a UK-wide case series
AU - Williams, Sophie T.
AU - Chatzikyriakou, Prodromos
AU - Carroll, Paul V.
AU - McGowan, Barbara M.
AU - Velusamy, Anand
AU - White, Gemma
AU - Obholzer, Rupert
AU - Akker, Scott
AU - Tufton, Nicola
AU - Casey, Ruth T.
AU - Maher, Eamonn R.
AU - Park, Soo-Mi
AU - Porteous, Mary
AU - Dyer, Rebecca
AU - Tan, Tricia
AU - Wernig, Florian
AU - Brady, Angela F.
AU - Kosicka-Slawinska, Monika
AU - Whitelaw, Benjamin C.
AU - Dorkins, Huw
AU - Lalloo, Fiona
AU - Brennan, Paul
AU - Carlow, Joseph
AU - Martin, Richard
AU - Mitchell, Anna L.
AU - Harrison, Rachel
AU - Hawkes, Lara
AU - Newell-Price, John
AU - Kelsall, Alan
AU - Igbokwe, Rebecca
AU - Adlard, Julian
AU - Schirwani, Schaida
AU - Davidson, Rosemarie
AU - Morrison, Patrick J.
AU - Chung, Teng-Teng
AU - Bowles, Christopher
AU - Izatt, Louise
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - gastrointestinal tumour
KW - paraganglioma
KW - phaeochromocytoma
KW - rare diseases
KW - succinate dehydrogenase
UR - https://onlinelibrary.wiley.com/doi/10.1111/cen.14594
U2 - 10.1111/cen.14594
DO - 10.1111/cen.14594
M3 - Article
C2 - 34558728
SN - 0300-0664
VL - 96
SP - 499
EP - 512
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 4
ER -