Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

Research output: Contribution to journalReview article

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Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. / Muth, A.; Crona, J.; Gimm, O.; Elmgren, A.; Filipsson, K.; Stenmark Askmalm, M.; Sandstedt, J.; Tengvar, M.; Tham, E.

In: Journal of Internal Medicine, Vol. 285, No. 2, 2019, p. 187-204.

Research output: Contribution to journalReview article

Harvard

Muth, A, Crona, J, Gimm, O, Elmgren, A, Filipsson, K, Stenmark Askmalm, M, Sandstedt, J, Tengvar, M & Tham, E 2019, 'Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma', Journal of Internal Medicine, vol. 285, no. 2, pp. 187-204. https://doi.org/10.1111/joim.12869

APA

Muth, A., Crona, J., Gimm, O., Elmgren, A., Filipsson, K., Stenmark Askmalm, M., Sandstedt, J., Tengvar, M., & Tham, E. (2019). Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. Journal of Internal Medicine, 285(2), 187-204. https://doi.org/10.1111/joim.12869

CBE

Muth A, Crona J, Gimm O, Elmgren A, Filipsson K, Stenmark Askmalm M, Sandstedt J, Tengvar M, Tham E. 2019. Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. Journal of Internal Medicine. 285(2):187-204. https://doi.org/10.1111/joim.12869

MLA

Vancouver

Author

Muth, A. ; Crona, J. ; Gimm, O. ; Elmgren, A. ; Filipsson, K. ; Stenmark Askmalm, M. ; Sandstedt, J. ; Tengvar, M. ; Tham, E. / Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. In: Journal of Internal Medicine. 2019 ; Vol. 285, No. 2. pp. 187-204.

RIS

TY - JOUR

T1 - Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

AU - Muth, A.

AU - Crona, J.

AU - Gimm, O.

AU - Elmgren, A.

AU - Filipsson, K.

AU - Stenmark Askmalm, M.

AU - Sandstedt, J.

AU - Tengvar, M.

AU - Tham, E.

PY - 2019

Y1 - 2019

N2 - Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.

AB - Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.

KW - molecular genetics

KW - neuroendocrine tumours

KW - pheochromocytoma

U2 - 10.1111/joim.12869

DO - 10.1111/joim.12869

M3 - Review article

C2 - 30536464

AN - SCOPUS:85060165378

VL - 285

SP - 187

EP - 204

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 1365-2796

IS - 2

ER -