# Otofaciocervical Syndrome and Its Overlap with Branchiootorenal Spectrum: An Integrated Literature Analysis of EYA1-Related Disorders, Including a Novel Case with an 8q13.2q13.3 Deletion

## TL;DR

This paper explores the connection between two rare genetic disorders, Otofaciocervical Syndrome and Branchiootorenal Spectrum Disorders, showing they are part of the same condition linked to the EYA1 gene.

## Contribution

The study confirms that Otofaciocervical Syndrome and Branchiootorenal Spectrum Disorders are allelic disorders caused by EYA1 gene defects.

## Key findings

- All EYA1 variant types can cause either Otofaciocervical Syndrome, Branchiootorenal Spectrum Disorders, or hybrid phenotypes.
- Renal anomalies are consistently present in Otofaciocervical Syndrome patients with EYA1 variants.
- The findings suggest that Otofaciocervical Syndrome and Branchiootorenal Spectrum Disorders are part of a single EYA1-related diagnostic spectrum.

## Abstract

Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial, auditory, and shoulder girdle anomalies. Its significant phenotypic overlap with branchiootorenal spectrum disorders (BORSD)—both linked to EYA1 (EYA transcriptional coactivator and phosphatase 1) gene defects—has raised questions about whether they are distinct entities or part of a single clinical spectrum. We report a novel OTFCS patient with a de novo microdeletion spanning EYA1 and review all published cases of EYA1-related disorders. Our analysis reveals that all EYA1 variant types (truncating, missense, CNV, etc.) can cause BORSD, OTFCS, or hybrid phenotypes, firmly supporting their status as allelic disorders. Crucially, all reported OTFCS patients with EYA1 variants had renal anomalies, a feature previously considered a hallmark of BORSD. We conclude that BORSD and OTFCS constitute a single EYA1-related diagnostic continuum. This reclassification mandates the development of follow-up protocols that integrate renal, otologic, and skeletal surveillance in EYA1-related disorders, including OTFCS, and refines prognostic and genetic counseling.