Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition characterized by multiple cutaneous and uterine leiomyomas and renal cell cancer (RCC). HLRCC is caused by germline pathogenic/likely pathogenic (P/LP) variants in the fumarate hydratase (FH) gene on chromosom...

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Main Authors: John J Orrego, Joseph A Chorny
Format: Article
Language:English
Published: Bioscientifica 2024-12-01
Series:Endocrinology, Diabetes & Metabolism Case Reports
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Online Access:https://edm.bioscientifica.com/view/journals/edm/2024/4/EDM-24-0073.xml
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author John J Orrego
Joseph A Chorny
author_facet John J Orrego
Joseph A Chorny
author_sort John J Orrego
collection DOAJ
description Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition characterized by multiple cutaneous and uterine leiomyomas and renal cell cancer (RCC). HLRCC is caused by germline pathogenic/likely pathogenic (P/LP) variants in the fumarate hydratase (FH) gene on chromosome 1q42.3, encoding the mitochondrial enzyme responsible for the conversion of fumarate to malate in the Krebs cycle. 0.6–3.1% of individuals with pheochromocytoma/paraganglioma (PCC/PGL) carry a germline variant in the FH gene. Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do. We described a female-to-male transgender with HLRCC who presented with large symptomatic uterine leiomyomas in the third decade of life and was diagnosed with a PCC 19 years after hysterectomy and with cutaneous leiomyomas and an aggressive form of RCC in the sixth decade of life. With the publication of this case and the review of the existent literature, and until more information becomes available, we would like to emphasize that clinicians should be aware of the possible connection between HLRCC and PCC/PGL, that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and finally that patients with HLRCC should be screened for PCC/PGL.
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spelling doaj-art-9a74973df4fa4060b7a66171c28169e92024-12-26T09:33:23ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732024-12-012024410.1530/EDM-24-00731Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variantsJohn J Orrego0Joseph A Chorny1Department of Endocrinology and Metabolism, Kaiser Foundation Health Plan of Colorado, Denver, Colorado, USADepartment of Pathology, Kaiser Foundation Health Plan of Colorado, Denver, Colorado, USAHereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition characterized by multiple cutaneous and uterine leiomyomas and renal cell cancer (RCC). HLRCC is caused by germline pathogenic/likely pathogenic (P/LP) variants in the fumarate hydratase (FH) gene on chromosome 1q42.3, encoding the mitochondrial enzyme responsible for the conversion of fumarate to malate in the Krebs cycle. 0.6–3.1% of individuals with pheochromocytoma/paraganglioma (PCC/PGL) carry a germline variant in the FH gene. Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do. We described a female-to-male transgender with HLRCC who presented with large symptomatic uterine leiomyomas in the third decade of life and was diagnosed with a PCC 19 years after hysterectomy and with cutaneous leiomyomas and an aggressive form of RCC in the sixth decade of life. With the publication of this case and the review of the existent literature, and until more information becomes available, we would like to emphasize that clinicians should be aware of the possible connection between HLRCC and PCC/PGL, that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and finally that patients with HLRCC should be screened for PCC/PGL.https://edm.bioscientifica.com/view/journals/edm/2024/4/EDM-24-0073.xmlendocrine cancersadrenalrare diseases/syndromes
spellingShingle John J Orrego
Joseph A Chorny
Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
Endocrinology, Diabetes & Metabolism Case Reports
endocrine cancers
adrenal
rare diseases/syndromes
title Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
title_full Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
title_fullStr Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
title_full_unstemmed Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
title_short Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants
title_sort hereditary leiomyomatosis and renal cell cancer hlrcc pheochromocytoma pcc paraganglioma pgl and germline fumarate hydratase fh variants
topic endocrine cancers
adrenal
rare diseases/syndromes
url https://edm.bioscientifica.com/view/journals/edm/2024/4/EDM-24-0073.xml
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AT josephachorny hereditaryleiomyomatosisandrenalcellcancerhlrccpheochromocytomapccparagangliomapglandgermlinefumaratehydratasefhvariants