Abstract: SA-PO0652
Branchio-Oto-Renal Spectrum Disorder: Progressive Genetic Nephropathy with Expanded Phenotypic Presentation in a Nephrology Population
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Hendricks, Emily, Natera, Inc., Austin, Texas, United States
- Vance, Cassie, Natera, Inc., Austin, Texas, United States
- Pereira, Tanya, Boston Children's Health Physicians, Hawthorne, New York, United States
- Pitman, Tessa R., Natera, Inc., Austin, Texas, United States
- Westemeyer, Margaret, Natera, Inc., Austin, Texas, United States
- Raible, Darbey, Natera, Inc., Austin, Texas, United States
- Hager, Megan M., Natera, Inc., Austin, Texas, United States
- Conway, Mary E., Natera, Inc., Austin, Texas, United States
- Punj, Sumit, Natera, Inc., Austin, Texas, United States
- Stein, Quinn, Natera, Inc., Austin, Texas, United States
Background
Branchio-Oto-Renal Spectrum Disorder (BORSD) is a rare autosomal dominant condition caused predominantly by variants in EYA1, with an estimated prevalence of 1 in 40,000 and is characterized by hearing loss, branchial anomalies, and renal malformations. Here, we aimed to evaluate the prevalence of BORSD in a large chronic kidney disease (CKD) population and assess the (extra)renal features, diagnostic patterns, and CKD progression.
Methods
Patients who underwent genetic testing with the RenasightTM test and had a positive result for a (likely) pathogenic (P/LP) variant in EYA1 were identified. A survey was sent to the providers to gather additional information regarding renal anomalies, syndromic features, and family history. CKD staging information was obtained from surveys or test requisition forms (TRFs).
Results
Among 142,820 individuals tested, 58 had P/LP variants in EYA1. Among 42 cases with reported CKD stage; 45.2% (n=19) had CKD1-2 and 47.6% (n=20) had CKD3-CKD5/ESRD; and 7.4% (n=3) had CKD of an unspecified stage. The average age among cases with CKD 1-2 and CKD 3-5 was 19.4 and 35.0 years, respectively.
Of 33 surveyed cases, 54.5% were suspected or known to have BORSD at the time of testing. Renal structural kidney anomalies were present in 45.5%, including agenesis (27.3%), dysplasia (36.3%), and hypoplasia (33.3%); proteinuria was reported in 30.3%. Extra-renal features included hearing loss (51.5%), branchial anomalies (18.2%), and preauricular pits/tags (31.3%). Atypical features reported such as developmental delay (6.1%), could suggest phenotypic expansion. Family history of renal disease was noted in 57.6% of cases.
Conclusion
BORSD may be significantly underrecognized in adult CKD populations, particularly those without syndromic features. In this CKD cohort, the prevalence of BORSD was 1:2,380, with the condition suspected in about half of cases prior to testing, underscoring the importance of broader genetic screening. The patients who had later CKD stages were in their fourth decade of life, suggesting that BORSD is a progressive genetic nephropathy. These findings support early detection and long-term monitoring through nephrology-genetics collaboration.
Funding
- Commercial Support – Natera, Inc.