Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant
IntroductionPheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline varian...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.609263/full |
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| author | Diana Borges Duarte Lia Ferreira Ana P. Santos Cláudia Costa Jorge Lima Jorge Lima Jorge Lima Catarina Santos Mariana Afonso Manuel R. Teixeira Manuel R. Teixeira Rui Carvalho Maria Helena Cardoso |
| author_facet | Diana Borges Duarte Lia Ferreira Ana P. Santos Cláudia Costa Jorge Lima Jorge Lima Jorge Lima Catarina Santos Mariana Afonso Manuel R. Teixeira Manuel R. Teixeira Rui Carvalho Maria Helena Cardoso |
| author_sort | Diana Borges Duarte |
| collection | DOAJ |
| description | IntroductionPheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals.Case presentationThe first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene.ConclusionThis case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk. |
| first_indexed | 2024-12-14T18:58:01Z |
| format | Article |
| id | doaj.art-0b18960c80204cdaabc5ac61bbf7bf59 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-14T18:58:01Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-0b18960c80204cdaabc5ac61bbf7bf592022-12-21T22:51:02ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-03-011210.3389/fendo.2021.609263609263Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious VariantDiana Borges Duarte0Lia Ferreira1Ana P. Santos2Cláudia Costa3Jorge Lima4Jorge Lima5Jorge Lima6Catarina Santos7Mariana Afonso8Manuel R. Teixeira9Manuel R. Teixeira10Rui Carvalho11Maria Helena Cardoso12Department of Endocrinology, Centro Hospitalar Universitário do Porto (CHUP), Porto, PortugalDepartment of Endocrinology, Centro Hospitalar Universitário do Porto (CHUP), Porto, PortugalDepartment of Endocrinology, Instituto Português de Oncologia Francisco Gentil (IPOFG), Porto, PortugalDepartment of Endocrinology, Instituto Português de Oncologia Francisco Gentil (IPOFG), Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIpatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, PortugalFaculty of Medicine, University of Porto, Porto, PortugalDepartment of Genetics, Instituto Português de Oncologia Francisco Gentil (IPOFG), Porto, PortugalDepartment of Pathology, Instituto Português de Oncologia Francisco Gentil (IPOFG), Porto, PortugalDepartment of Genetics, Instituto Português de Oncologia Francisco Gentil (IPOFG), Porto, PortugalBiomedical Sciences Institute, University of Porto, Porto, PortugalDepartment of Endocrinology, Centro Hospitalar Universitário do Porto (CHUP), Porto, PortugalDepartment of Endocrinology, Centro Hospitalar Universitário do Porto (CHUP), Porto, PortugalIntroductionPheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals.Case presentationThe first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene.ConclusionThis case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk.https://www.frontiersin.org/articles/10.3389/fendo.2021.609263/fullMAX genepheochromocytomahereditaryneuroblastomaparaganglioma |
| spellingShingle | Diana Borges Duarte Lia Ferreira Ana P. Santos Cláudia Costa Jorge Lima Jorge Lima Jorge Lima Catarina Santos Mariana Afonso Manuel R. Teixeira Manuel R. Teixeira Rui Carvalho Maria Helena Cardoso Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant Frontiers in Endocrinology MAX gene pheochromocytoma hereditary neuroblastoma paraganglioma |
| title | Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant |
| title_full | Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant |
| title_fullStr | Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant |
| title_full_unstemmed | Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant |
| title_short | Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant |
| title_sort | case report pheochromocytoma and synchronous neuroblastoma in a family with hereditary pheochromocytoma associated with a max deleterious variant |
| topic | MAX gene pheochromocytoma hereditary neuroblastoma paraganglioma |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.609263/full |
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