A Case of Branchio-oto Syndrome Caused by EYA1 Mutation

Abstract

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchiogenic malformations, hearing loss, and renal malformations. Subjects with BOR syndrome who do not have renal malformations are said to have branchio-oto syndrome (BOS). Here, we present a case of BOS caused by an EYA1 mutation.

A five-month-old boy was brought to our hospital for an audiologic assessment. He had hypoplasia of the right pinna and preauricular pits in the crus of the helix on both sides. Conditioned orientation response audiometry and auditory steady state response examination revealed bilateral moderate hearing loss. High-resolution computed tomography suggested the absence of the long process of the incus, cochlear hypoplasia (incomplete partition, type-II), and hypoplasia of the lateral semicircular canals of both ears. His grandfather also had preauricular pits in the crus of the helix on both sides and bilateral severe-to-profound mixed hearing loss. Physical examination revealed branchial fistulae. His mother had surgical scars on the crus of the helix of both sides and in the neck due to the excision of preauricular and branchial fistulae. Pure-tone audiometry revealed bilateral moderate sensorineural hearing loss. On the basis of these findings, we suspected that the family suffered from BOS. Genetic analysis identified a heterozygous nonsense mutation, p.Arg264X, in the EYA1 gene, mutation of which is known to cause BOR syndrome and BOS. The results showed that the boy had BOS caused by an EYA1 mutation.

BOR syndrome and BOS are inherited in an autosomal dominant manner. Clinicians should inform the family members that the offspring of an affected subject are at a 50% risk of inheriting the pathogenic variant. Extreme variability is observed in the presence, severity, and type of branchial anomalies and otologic/renal abnormalities, even among individuals of the same family. Otologists and audiologists should be familiar with BOR syndrome and BOS, since the initial consultation in most cases of these hereditary disorders may be with otologists/audiologists.