Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.
OBJECTIVE: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations. DESIGN: Retrospective case-series. PATIENTS:...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
2008
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| _version_ | 1826258196774256640 |
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| author | Srirangalingam, U Walker, L Khoo, B MacDonald, F Gardner, D Wilkin, T Skelly, R George, E Spooner, D Monson, J Grossman, AB Akker, SA Pollard, P Plowman, N Avril, N Berney, D Burrin, J Reznek, R Kumar, V Maher, E Chew, S |
| author_facet | Srirangalingam, U Walker, L Khoo, B MacDonald, F Gardner, D Wilkin, T Skelly, R George, E Spooner, D Monson, J Grossman, AB Akker, SA Pollard, P Plowman, N Avril, N Berney, D Burrin, J Reznek, R Kumar, V Maher, E Chew, S |
| author_sort | Srirangalingam, U |
| collection | OXFORD |
| description | OBJECTIVE: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations. DESIGN: Retrospective case-series. PATIENTS: Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres. MEASUREMENTS: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management. RESULTS: Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension. CONCLUSION: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease. |
| first_indexed | 2024-03-06T18:30:11Z |
| format | Journal article |
| id | oxford-uuid:0958e865-b210-41dd-ad14-28dcf7ddd798 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:30:11Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:0958e865-b210-41dd-ad14-28dcf7ddd7982022-03-26T09:18:09ZClinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0958e865-b210-41dd-ad14-28dcf7ddd798EnglishSymplectic Elements at Oxford2008Srirangalingam, UWalker, LKhoo, BMacDonald, FGardner, DWilkin, TSkelly, RGeorge, ESpooner, DMonson, JGrossman, ABAkker, SAPollard, PPlowman, NAvril, NBerney, DBurrin, JReznek, RKumar, VMaher, EChew, SOBJECTIVE: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations. DESIGN: Retrospective case-series. PATIENTS: Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres. MEASUREMENTS: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management. RESULTS: Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension. CONCLUSION: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease. |
| spellingShingle | Srirangalingam, U Walker, L Khoo, B MacDonald, F Gardner, D Wilkin, T Skelly, R George, E Spooner, D Monson, J Grossman, AB Akker, SA Pollard, P Plowman, N Avril, N Berney, D Burrin, J Reznek, R Kumar, V Maher, E Chew, S Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title | Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title_full | Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title_fullStr | Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title_full_unstemmed | Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title_short | Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. |
| title_sort | clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase b sdh b gene mutation carriers |
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