The Branchio-Oto-Renal Syndrome

Abstract

Publisher Summary This chapter presents information on the diagnosis, genetics, and most characteristic symptoms of branchio-oto-renal (BOR) syndrome. The BOR syndrome is a Mendelian developmental disorder with branchial, otic, and renal manifestations. Hearing loss is the major feature of BOR syndrome and occurs in 93% of patients. The age of onset varies from early childhood to young adulthood. The impairment can be conductive, sensorineural, or mixed. Branchial cysts or fistulas are seen in approximately 65% of patients. These hallmark features may be either uni- or bilateral and are usually located on the external lower third of the neck, anterior to the sternocleidomastoid muscle. The clinical diagnosis of BOR syndrome is based on the presence of two or more of the findings such as pre-auricular pits, pinnae deformities, branchial fistulas, hearing loss, and renal anomalies. Genetic testing can confirm a clinical diagnosis of BOR syndrome and provide genetic recurrence risk information to families. There are at least 61 different mutations in the EYA1 gene identified in BOR syndrome patients. The mutations include large and small deletions and nonsense, missense, frameshift, aberrant splicing and exon skipping mutations. Mutations in the EYA1 gene are detected in patients with branchial and otic anomalies, but without the renal anomalies (BO syndrome), thus demonstrating that BOR and BO syndromes are allelic. The clinical signs of BOR syndrome are indicative of an early developmental defect of the branchial arch apparatus, the otic vesicle and/or surrounding periotic mesenchyme and the mesonephros/metanephros, taking place between the 4th and 10th weeks of human embryonic development. It is therefore very likely that EYA1 and SIX1 have critical roles in the development of these tissues.