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ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Adrenal Endocrinology
Volume 15 - 2024 |
doi: 10.3389/fendo.2024.1442691
Genotype and clinical phenotype characteristics of MAX germline mutation-associated pheochromocytoma/paraganglioma syndrome
Provisionally accepted- 1 Department of Urology, The 903rd Hospital of The Chinese People’s Liberation Army, Hangzhou, China
- 2 Department of Urology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Enze Hospital, Taizhou Enze Medical Center (Group), Hangzhou, Jiangsu Province, China
- 3 Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
- 4 Department of Urology, First Hospital of Jiaxing, Jiaxing, China
Objective: The aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation–associated pheochromocytoma (PCC) and paraganglioma (PGL). Methods: We retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously. Results: There were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study. Conclusion: MAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell–derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.
Keywords: Multiple Endocrine Neoplasia, Pheochromocytoma, Paraganglioma, Genealogy, MAX gene
Received: 02 Jun 2024; Accepted: 15 Aug 2024.
Copyright: © 2024 Lian, Lu, Xudong, Zhang, Wang, He, Yu, Li, Wang, Chen and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jun Lu, Department of Urology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Enze Hospital, Taizhou Enze Medical Center (Group), Hangzhou, Jiangsu Province, China
Yiming Zhang, Department of Urology, The 903rd Hospital of The Chinese People’s Liberation Army, Hangzhou, China
Wei Wang, Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
Yi He, Department of Urology, First Hospital of Jiaxing, Jiaxing, China
Feiping Li, Department of Urology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Enze Hospital, Taizhou Enze Medical Center (Group), Hangzhou, Jiangsu Province, China
Junwei Wang, Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China
Wei-Ying Chen, Department of Urology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Enze Hospital, Taizhou Enze Medical Center (Group), Hangzhou, Jiangsu Province, China
Xiao-ping Qi, Department of Urology, The 903rd Hospital of The Chinese People’s Liberation Army, Hangzhou, China
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