Clinical and molecular features of renal and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS): Case series and literature review

Ruth T. Casey*, Anne Y. Warren, Jose Ezequiel Martin, Benjamin G. Challis, Eleanor Rattenberry, James Whitworth, Katrina A. Andrews, Thomas Roberts, Graeme R. Clark, Hannah West, Philip S. Smith, France M. Docquier, Fay Rodger, Vicki Murray, Helen L. Simpson, Yvonne Wallis, Olivier Giger, Maxine Tran, Susan Tomkins, Grant D. StewartSoo Mi Park, Emma R. Woodward, Eamonn R. Maher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Context: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. Objective: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. Design: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. Results: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. Conclusion: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition.

Original languageEnglish
Pages (from-to)4013-4022
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
Early online date28 Jul 2017
Publication statusPublished - Nov 2017


Dive into the research topics of 'Clinical and molecular features of renal and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS): Case series and literature review'. Together they form a unique fingerprint.

Cite this