Balkan Journal of Medical Genetics

CASE REPORT OF A NOVEL MUTATION OF THE EYA1 GENE IN A PATIENT WITH BRANCHIO-OTO-RENAL SYNDROME
Spahiu L, Merovci B, Ismaili Jaha V, Batalli Këpuska A, Jashari H
*Corresponding Author: Dr. Besart Merovci, Pediatric Clinic, University Clinical Center of Kosovo, Pristina, Republic of Kosovo. Tel: +377-44-161-538. E-mail: m_besart@hotmail.com
page: 91

DISCUSSION

The incidence of BOR is estimated between 1:40,000 to 1:700,000. However, the incidence is higher among deaf children [2]. Fraser et al. [3] reported that 2.0% of deaf patients and 6.0% of ESRD patients have genetically proven BOR syndrome. Furthermore, more than 80 disorders presenting with sensorineural deafness and renal disturbances have been reported. Thus, phenotypic criteria should often be complemented with genetic analysis to avoid misdiagnosis. Major phenotypic anomalies that occur in more than 20.0% of patients are: sensorineural or mixed hearing impairment (95.4%), followed by malformed auricles (86.8%), second branchial arch fistula/cyst (86.5%), preauricular sinus (87.0%), and renal anomalies ranging from mild hypoplasia to complete absence (58.3%) [4]. In addition, phenotypic anomalies occurring in less than 20.0% of patients are considered minor, i.e., pre-auricular tags, lacrimal duct aplasia, retrognathia, short palate, palatoschisis, facial paralysis, meatal atresia, etc. Likewise, at least three major criteria or two major and two minor criteria or one major criteria plus an affected first degree relative must be fulfilled to meet the clinical criteria for a BOR syndrome diagnosis [5]. Branchial fistulae, pre-auricular tags and conductive hearing impairment were present in all three members of the presented family. Also, renal abnormalities in the form of unilateral hypoplasia (father and sister) and bilateral hypoplasia (our patient) corresponding with BOR syndrome diagnosis were confirmed. However, variable phenotypic expressivity within families due to reduced penetrance has been observed [6]. Pierides et al. [1] followed 20 members of a three-generation Greek- Cypriot family for nearly three decades, and found only four members manifesting with all four BOR syndrome features of brachial fistulae, hearing loss, pre-auricular pits and renal abnormalities leading to renal failure. In 1992, the BOR gene was mapped to chromosome 8q12-22 [7]. Five years later, the BOR gene was identified as the human homologue of the Drosophila eyes absent gene (eya) and called it EYA1 [8]. However, mutations and deletions of the EYE1 gene have been identified in only about 40.0% of individuals with the BOR phenotype. Mutations of other genes such as SIX1 and SIX5 have also been related to BOR syndrome, but at a much lower incidence [9-11]. At least 80 mutations of the EYE1 gene resulting in BOR syndrome [12], suggests that the type of mutation has a dosage effect, explaining the variable ex-pressivity within families. Further studies are needed to better understand the phenotypical expressivity of BOR syndrome. Branchial anomalies account for up to 45.0% of neck pathologies. It is usually the main complaint that families seek medical attention for [13]. Hence, BOR syndrome should always be considered in patients with branchial fistula and/or external ear anomalies or similar findings in other family members. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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