Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes

Diana E. Benn, Anne Paule Gimenez-Roqueplo, Jennifer R. Reilly, Jérôme Bertherat, John Burgess, Karen Byth, Michael Croxson, Patricia L.M. Dahia, Marianne Elston, Oliver Gimm, David Henley, Philippe Herman, Victoria Murday, Patricia Niccoli-Sire, Janice L. Pasieka, Vincent Rohmer, Kathy Tucker, Xavier Jeunemaitre, Deborah J. Marsh, Pierre François Plouin & 1 others Bruce G. Robinson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology,anddisease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. Results: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereasSDHDmutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43SDHBand 19SDHDmutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated agerelated penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). Conclusions: Forclinical follow-up,featuresofSDHBmutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.

Original languageEnglish
Pages (from-to)827-836
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number3
DOIs
Publication statusPublished - 1 Mar 2006
Externally publishedYes

Cite this

Benn, D. E., Gimenez-Roqueplo, A. P., Reilly, J. R., Bertherat, J., Burgess, J., Byth, K., ... Robinson, B. G. (2006). Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. Journal of Clinical Endocrinology and Metabolism, 91(3), 827-836. https://doi.org/10.1210/jc.2005-1862
Benn, Diana E. ; Gimenez-Roqueplo, Anne Paule ; Reilly, Jennifer R. ; Bertherat, Jérôme ; Burgess, John ; Byth, Karen ; Croxson, Michael ; Dahia, Patricia L.M. ; Elston, Marianne ; Gimm, Oliver ; Henley, David ; Herman, Philippe ; Murday, Victoria ; Niccoli-Sire, Patricia ; Pasieka, Janice L. ; Rohmer, Vincent ; Tucker, Kathy ; Jeunemaitre, Xavier ; Marsh, Deborah J. ; Plouin, Pierre François ; Robinson, Bruce G. / Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 3. pp. 827-836.
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title = "Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes",
abstract = "Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology,anddisease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. Results: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereasSDHDmutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43SDHBand 19SDHDmutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated agerelated penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). Conclusions: Forclinical follow-up,featuresofSDHBmutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.",
author = "Benn, {Diana E.} and Gimenez-Roqueplo, {Anne Paule} and Reilly, {Jennifer R.} and J{\'e}r{\^o}me Bertherat and John Burgess and Karen Byth and Michael Croxson and Dahia, {Patricia L.M.} and Marianne Elston and Oliver Gimm and David Henley and Philippe Herman and Victoria Murday and Patricia Niccoli-Sire and Pasieka, {Janice L.} and Vincent Rohmer and Kathy Tucker and Xavier Jeunemaitre and Marsh, {Deborah J.} and Plouin, {Pierre Fran{\cc}ois} and Robinson, {Bruce G.}",
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Benn, DE, Gimenez-Roqueplo, AP, Reilly, JR, Bertherat, J, Burgess, J, Byth, K, Croxson, M, Dahia, PLM, Elston, M, Gimm, O, Henley, D, Herman, P, Murday, V, Niccoli-Sire, P, Pasieka, JL, Rohmer, V, Tucker, K, Jeunemaitre, X, Marsh, DJ, Plouin, PF & Robinson, BG 2006, 'Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 3, pp. 827-836. https://doi.org/10.1210/jc.2005-1862

Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. / Benn, Diana E.; Gimenez-Roqueplo, Anne Paule; Reilly, Jennifer R.; Bertherat, Jérôme; Burgess, John; Byth, Karen; Croxson, Michael; Dahia, Patricia L.M.; Elston, Marianne; Gimm, Oliver; Henley, David; Herman, Philippe; Murday, Victoria; Niccoli-Sire, Patricia; Pasieka, Janice L.; Rohmer, Vincent; Tucker, Kathy; Jeunemaitre, Xavier; Marsh, Deborah J.; Plouin, Pierre François; Robinson, Bruce G.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 3, 01.03.2006, p. 827-836.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes

AU - Benn, Diana E.

AU - Gimenez-Roqueplo, Anne Paule

AU - Reilly, Jennifer R.

AU - Bertherat, Jérôme

AU - Burgess, John

AU - Byth, Karen

AU - Croxson, Michael

AU - Dahia, Patricia L.M.

AU - Elston, Marianne

AU - Gimm, Oliver

AU - Henley, David

AU - Herman, Philippe

AU - Murday, Victoria

AU - Niccoli-Sire, Patricia

AU - Pasieka, Janice L.

AU - Rohmer, Vincent

AU - Tucker, Kathy

AU - Jeunemaitre, Xavier

AU - Marsh, Deborah J.

AU - Plouin, Pierre François

AU - Robinson, Bruce G.

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology,anddisease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. Results: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereasSDHDmutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43SDHBand 19SDHDmutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated agerelated penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). Conclusions: Forclinical follow-up,featuresofSDHBmutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.

AB - Context: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma/paraganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Objective: Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. Design, Setting, and Participants: The International SDH Consortium studied 116 individuals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Main Outcome Measures: Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology,anddisease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. Results: SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereasSDHDmutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43SDHBand 19SDHDmutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively; P = 0.3). However, when all mutation carriers were included (n = 112), the estimated agerelated penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). Conclusions: Forclinical follow-up,featuresofSDHBmutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.

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