Rare kidney disease diagnostic advances recognized for clinical impact
Recent discoveries are transforming how doctors diagnose Birt-Hogg-Dubé syndrome, a rare inherited condition that increases the risk of kidney tumors. By closing gaps in genetic testing and improving tumor classification, the research enables more accurate diagnosis and better-informed care for patients and families. The impact of the study was recently recognized when European Urology named it the top translational paper of 2025.
Originally published in April 2025 by a group of Mayo Clinic physicians and scientists, “Renal Neoplasia in Brit-Hogg-Dube Syndrome: Integrated Histopathologic, Bulk, and Single-cell Transcriptomic Analysis,” set out to refine cancer screening criteria and strengthen genetic testing strategies.
“The recognition is gratifying, but what matters most to our team is what this work means for patients and the clinicians caring for them,” says Sounak Gupta, M.B.B.S., Ph.D., lead author of the study, vice chair of research and innovation in the Division of Anatomic Pathology, and vice chair of oncology practice in the Division of Laboratory Genetics and Genomics at Mayo Clinic in Rochester.
Among the takeaways benefiting patients and clinicians are:
- Genetic testing gaps: The research revealed that existing testing failed to identify the entire spectrum of variants in the pathogenic folliculin gene (FLCN). Genetic variation in the gene has been identified as the underlying cause of Birt-Hogg-Dubé syndrome. Expanding testing to identify the entire spectrum of FLCN variants will help more people receive an accurate diagnosis.
- Symptoms matter more than age: A top takeaway was that symptoms matter more than age in informing testing for the syndrome. Doctors should focus less on how old someone is and more on whether they have multiple or bilateral kidney tumors, which is a strong clue for inherited risk.
- Comprehensive guidance to classify tumors: Two-thirds of patients in the study were diagnosed only after their kidney tumors were removed, making proper diagnosis for these tumors critical. The researchers also found that kidney tumors associated with Birt-Hogg-Dubé syndrome are not a blend of two known tumor types but instead represent a unique tumor type. Still, these tumors often resemble other kidney cancers. The team used advanced genetic analysis to develop a comprehensive approach to reliably distinguish kidney tumors in patients with FLCN variants and Birt-Hogg-Dubé syndrome from similar kidney cancers.
- Improved risk insight: Most kidney tumors related to Birt-Hogg-Dubé syndrome were found to be slow-growing, but the study also helps identify rare tumors that may behave more aggressively and need closer monitoring.
The discoveries in this study are already driving tangible changes. For example, Mayo Clinic Laboratories updated its Birt-Hogg-Dube syndrome test (Mayo ID: BHDZ) to fill the FLCN testing gap identified in the study, and it launched two new tests to help assess and screen kidney tumors (Mayo IDs: GPNMB and SOX9).
“This is a great example of how innovation builds on itself,” says Dr. Gupta. “Previously developed tests supported this research that led to more discoveries to further improve how we diagnosis this syndrome.”
The study marks an important step forward in recognizing and managing Birt-Hogg-Dubé syndrome. By improving genetic testing, clarifying tumor classification, and identifying which tumors need closer monitoring, the research gives clinicians more precise guidance. As these discoveries move into clinical practice, they promise more accurate diagnoses and better care for patients.
