Genetic and Surgical Management of Branchio-Oto-Renal Syndromes

Branchio-oto-renal (BOR) syndromes encompass a spectrum of autosomal dominant conditions characterised by branchial arch anomalies, ear malformations with varying degrees of hearing loss, and renal dysplasia. Genetic management has advanced through the identification of pathogenic variants in the EYA1 and SIX gene families, aided by next-generation sequencing approaches that detect both point mutations and structural rearrangements. Early molecular diagnosis enables personalised counselling and surveillance of renal function. Surgical management requires a multidisciplinary strategy: excision of branchial clefts and preauricular sinuses to prevent recurrent infections, middle ear reconstruction when feasible, and cochlear implantation for severe sensorineural deficits. This integrated approach improves auditory rehabilitation, reduces morbidity, and informs long-term monitoring of renal outcomes.

Research from Nature Portfolio

Recent studies have expanded understanding of SIX1 variants in atypical presentations, identifying novel heterozygous variants that underlie non-syndromic hearing loss and attenuated branchio-otic features. Functional analyses reveal that mutant SIX1 proteins exhibit varying deficiencies in DNA binding and transcriptional activation within the EYA1–SIX1 regulatory complex. These findings refine genotype–phenotype correlations and underscore the necessity of molecular assessment to guide diagnosis and inform potential therapeutic targets.

Genetic and Surgical Management of Branchio-Oto-Renal Syndromes publication trend

The graph below shows the total number of articles in genetic and surgical management of branchio-oto-renal syndromes across all publications each year (not limited to Nature Index journals).

Technical terms

Branchio-oto-renal syndrome (BOR): A hereditary disorder characterised by branchial arch defects, ear malformations and renal anomalies.

EYA1: A gene encoding a transcriptional co-activator essential for embryonic development of the ear and kidney.

SIX1: A homeodomain transcription factor that forms a regulatory complex with EYA1 to control gene expression in otic and branchial tissues.

Whole-genome sequencing (WGS): A high-throughput method for comprehensive detection of genomic variants across the entire DNA sequence.

Multiplex ligation-dependent probe amplification (MLPA): A technique for identifying copy-number variations in specific genomic regions.

Cochlear implantation: A surgical intervention that places an electronic device to stimulate the auditory nerve, bypassing damaged cochlear structures.

Supra-auricular approach: A surgical technique for excision of preauricular sinuses involving an incision above the ear to ensure complete tract removal.

References

1. Genomic Landscape of Branchio-Oto-Renal Syndrome through Whole-Genome Sequencing: A Single Rare Disease Center Experience in South Korea. International Journal of Molecular Sciences (2024).
2. Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea. Scientific Reports (2023).
3. Supra-auricular versus Sinusectomy Approaches for Preauricular Sinuses. International Archives of Otorhinolaryngology (2016).
4. Mutational Analysis of EYA1, SIX1 and SIX5 Genes and Strategies for Management of Hearing Loss in Patients with BOR/BO Syndrome. PLOS ONE (2013).