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Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

Muth, A.; Crona, J.; Gimm, O.; Elmgren, A.; Filipsson, K. LU ; Stenmark Askmalm, M. LU ; Sandstedt, J.; Tengvar, M. and Tham, E. (2019) In Journal of Internal Medicine 285(2). p.187-204
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
molecular genetics, neuroendocrine tumours, pheochromocytoma
in
Journal of Internal Medicine
volume
285
issue
2
pages
187 - 204
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • scopus:85060165378
ISSN
0954-6820
DOI
10.1111/joim.12869
language
English
LU publication?
yes
id
e4e9bebd-7483-4ae7-b125-6fe7cf831990
date added to LUP
2019-01-29 14:53:18
date last changed
2019-02-20 11:45:10
@article{e4e9bebd-7483-4ae7-b125-6fe7cf831990,
  abstract     = {<p>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.</p>},
  author       = {Muth, A. and Crona, J. and Gimm, O. and Elmgren, A. and Filipsson, K. and Stenmark Askmalm, M. and Sandstedt, J. and Tengvar, M. and Tham, E.},
  issn         = {0954-6820},
  keyword      = {molecular genetics,neuroendocrine tumours,pheochromocytoma},
  language     = {eng},
  number       = {2},
  pages        = {187--204},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma},
  url          = {http://dx.doi.org/10.1111/joim.12869},
  volume       = {285},
  year         = {2019},
}