Branchio-otorenal (BOR) syndrome is an autosomal dominant disorder with incomplete penetrance and variable expression characterized by branchial, otic, and renal anomalies. Mutations in the EYA1 gene have been associated with BOR syndrome. In order to demonstrate the utility and limitations of EYA1 testing, clinical features and test results in our BOR syndrome patients were reviewed. A retrospective chart review was conducted on 8 patients identified with BOR syndrome based on diagnostic criteria described by Chang and Smith et al (2004) and in whom EYA1 testing was completed. The clinical features of EYA1 mutation-positive and EYA1 mutation-negative patients were then compared. EYA1 mutations, S251X and W541X, were identified in 2 of the 8 patients. Features present in both EYA1 mutation-positive patients were hearing loss, external ear anomalies (ie, microtia and simple or cupped ears), and branchial anomalies. These findings were less common in the EYA1 mutation-negative patients: hearing loss 83% (5/6), external ear anomalies 67% (4/6), and branchial anomalies 50% (3/6). Preauricular pits, renal anomalies, inner or middle ear malformations, asymmetric crying facies, and a family history suggestive of BOR syndrome were present in at least one of the EYA1 mutation-positive patients. In the EYA1 mutation-negative patients, 83% (5/6) had a family history suggestive of BOR syndrome, 67% (4/6) had preauricular pits, and 17% (1/6) had asymmetric crying facies. Imaging of the temporal bones and renal ultrasound were completed in 5 of the 6 EYA1 mutation-negative patients. Inner or middle ear malformations and renal anomalies were identified in 80% (4/5) and 60% (3/5), respectively. Preauricular tags were present in 50% (3/6) of the EYA1 mutation-negative patients and none of the patients with identified mutations. Although this is a small study, EYA1 mutations are more likely identified in patients with branchial anomalies. Other common features, including preauricular pits, renal anomalies, and various ear malformations, were not alone highly predictive. Asymmetric crying facies, which was present in 2 of the 8 patients, may also be a more commonly associated feature in BOR syndrome than previously described. This study illustrates the various major and minor phenotypic features reported in individuals with BOR syndrome and the continued challenge in identifying genetic changes responsible for this condition and other forms of syndromic hearing loss.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.