Journal of Pediatric Surgery (2009) 44, 623–625
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From a branchial fistula to a branchiootorenal syndrome: a case report and review of the literature Emrah Senel a,⁎, Hatice Kocak b , Fatih Akbiyik a , Guleser Saylam c , Basak Nadide Gulleroglu d , Saliha Senel e a
Department of Pediatric Surgery, Diskapi Childrenʼs Hospital, 06110 Ankara, Turkey Department of Genetics, Diskapi Childrenʼs Hospital, 06110 Ankara, Turkey c Department of Pediatric Ear Nose Throat, Diskapi Hospital, 06110 Ankara, Turkey d Department of Pediatric Radiology, Diskapi Childrenʼs Hospital, 06110 Ankara, Turkey e Department of Pediatrics, Dr Sami Ulus Childrenʼs Hospital, 06110 Ankara, Turkey b
Received 25 August 2008; revised 5 October 2008; accepted 8 October 2008
Key words: Branchiootorenal syndrome; Branchial anomalies; Hearing impairment; Preauricular pit
Abstract Branchial abnormalities constitute 32% to 45% of all neck pathologies in children. They may be a part of branchiootorenal (BOR) syndrome, which is characterized by branchial arch anomalies, preauricular pits, hearing impairment, and renal malformations. Typically, the management of a branchial fistula does not necessarily require an extensive diagnostic workup. However, in patients with a branchial fistula associated with external ear anomalies on physical examination and/or a history of hearing loss and a similar history and findings in other family members, an additional workup should be performed to eliminate the possibility of BOR syndrome. The aim of this report is to make pediatric surgeons aware of the BOR syndrome in patients presenting with branchial arch anomalies. © 2009 Elsevier Inc. All rights reserved.
Cysts and sinuses of the neck constitute one of the most intriguing areas of pediatric pathology. The classic approach to most neck anomalies does not necessarily require an extensive workup, and the lesion can often be excised safely in a day surgery unit [1]. Occasionally, a branchial anomaly may be a part of branchiootorenal (BOR) syndrome, which was first described by Melnick et al [2] and Fraser et al [3]. It is characterized by branchial arch anomalies (branchial clefts, fistula, cysts), hearing impairment (malformations of the auricle with preauricular pits, conductive, or sensorineural hearing impairment), and renal malformations (urinary tract malformation, renal hypoplasia or agenesis,
renal dysplasia, renal cysts). It is a clinically and genetically heterogeneous disease that is transmitted in an autosomal dominant manner [4]. Only 1 of the 186 articles concerning BOR in the medical literature has been published in a pediatric surgery journal [5]. The aim of this report is to make pediatric surgeons aware of the BOR syndrome in patients presenting with branchial arch anomalies. Herein, we report the first Turkish family with BOR syndrome.
⁎ Corresponding author. Tel.: +90 312 5969696; fax: +90 312 3472330. E-mail address:
[email protected] (E. Senel).
A 6-year-old girl, the proband (IV-10), was referred to our pediatric surgery department because of bilateral second
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1. Case report
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branchial fistulae. Her father, who also had similar branchial fistulae, accompanied her. Physical examination of the neck revealed bilateral second branchial fistulae and bilateral preauricular pits. She had no history of otorrhea or otitis media but had a history of hearing loss. Conventional audiometry in the frequency range of 0.125 to 8 kHz and high frequency audiometry in the frequency range of 9 to 16 kHz were performed. The hearing thresholds were consistent with a mild conductive hearing loss for the left ear and moderate mixed hearing loss for the right ear. She had no history of renal pathology, but ultrasound examination revealed unilateral renal agenesis on the right side. Temporal bone computed tomography (CT) was performed to detect any middle and inner ear anomalies. The CT showed bilaterally enlarged internal auditory canals (IACs) that were not funnel shaped. Cochlear apical turns and horizontal semicircular canals were hypoplastic bilaterally. The right malleus and incus were hypoplastic. Microarray analysis detected an abnormality in the DNA of the peripheral blood specimen. Based on microarray analysis, the proband has a deletion of 8q13.3 within the EYA1 gene (OMIM 601653). Physical examination of the father (III-7), who was 44 years old, revealed bilateral preauricular fistula between the helix and tragal cartilage and also bilateral second branchial fistulae. The rest of physical examination was normal. Pure tone audiogram showed moderate and mixed hearing loss on the right ear and moderate hearing loss on the left ear. Ultrasound examination revealed no renal abnormality. Computed tomography of temporal bone revealed that IAC was enlarged bilaterally but not funnel shaped. Bilateral cochlear apical turns and the right basal turn were hypoplastic. Bilateral horizontal semicircular canals, left superior, and posterior semicircular canals were hypoplastic. The right incus was hypoplastic, and malleus and incus were dysplastic on the left side. The proband was operated upon in our pediatric surgery department for bilateral branchial fistula, and she was then referred to the pediatric nephrology and pediatric ear-nosethroat (ENT) departments. Pediatric nephrology recommended regular follow-up visits, and an operation was
Fig. 1
Pedigree of Turkish family with BOR syndrome.
scheduled for hearing loss by the pediatric ENT department. The father was also referred to an adult ENT department and an operation planned for his hearing loss as well. We have learned about 6 family members with branchial fistula or hearing loss other than the proband and father, according to information from the father and a family pedigree that was performed (Fig. 1). We attempted to examine the rest of the members of pedigree but could not acquire their consent.
2. Discussion Branchiootorenal syndrome is an automosal dominant disorder. The incidence is approximately 1 in 40,000 in the general population and 2% among profoundly deaf children [6]. At present, 89 families with BOR have been reported [7]. Reduced penetrance and variable expressivity has been observed [3]. Previous reports have shown a wide variation of clinical phenotypes between and within families [8]. Major diagnostic criteria are branchial anomalies, deafness, preauricular pits, and renal anomalies. Minor criteria are external ear anomalies, middle ear anomalies, inner ear anomalies, preauricular tags, facial asymmetry, and palate anomalies. To be classified as BOR, an affected individual must have at least 3 major criteria, 2 major criteria and at least 2 minor criteria, or one major criteria and an affected first-degree relative meeting the criteria for BOR syndrome [9]. Stinckens et al [10] reported the frequencies of the main features of BOR syndrome as follows: hearing impairment (95.4%), malformed auricles (86.8%), second branchial arch fistula/cyst (86.5%), preauricular sinus (87.0%), and renal anomalies (58.3%). Proband had shown all major criteria of BOR: bilateral branchial fistula, bilateral preauricular pits, unilateral renal agenesis, and deafness. The father had shown 3 major criteria: bilateral branchial fistula, bilateral preauricular pits, and deafness. Three loci were known to be associated with the BOR phenotype. The causative gene, EYA1, is located on the long arm of chromosome 8. Point mutations and deletions in EYA1 have been identified in approximately 40% of patients with BOR phenotype. Mutations have also been identified in the SIX1 and SIX5 genes, the products of which interact with EYA1 to form transcription factor complexes. However, the frequency of SIX1 and SIX5 is much lower [11-13]. Genetic analysis of the proband showed deletion within the EYA1 gene, which was compatible with observations in the literature. The severity of phenotype does not correlate with the type of mutation and is extremely variable even within families [7]. Hearing impairment has been reported in 95.4% of patients with BOR syndrome [10]. The hearing loss can be conductive, sensorineural, or mixed because of an otic anomaly of the outer, middle, or inner ear, and often, it is associated with preauricular tags or pits [14]. In our report, hearing impairment was detected in the proband and her
Branchial fistula to a BOR syndrome father, and according to the father, a history of hearing impairment was present in 5 of 6 affected family members. Temporal bone study on CT shows a wide variety of middle and inner ear malformations. The most common reported characteristics of BOR on CT were hypoplastic apical turn of the cochlea, facial nerve deviated to the medial side of the cochlea, funnel-shaped IAC, patulous eustachian tube, reduced middle ear cavity, a variety of ossicular anomalies, hypoplastic lateral semicircular canal, and enlarged vestibular aqueduct [14]. Facial and cochlear nerve abnormalities have also been reported in the BOR syndrome [15,16]. In addition to bilateral apical turn cochlea hypoplasia, bilateral horizontal semicircular canals, right malleus, and incus were hypoplastic, and the IAC was not funnel shaped in the proband. Bilateral horizontal semicircular canals, left superior and posterior semicircular canals, and right incus were hypoplastic; left malleus and incus were dysplastic in addition to bilateral apical turn cochlea hypoplasia in the father, which has not been previously reported. Branchial anomalies constitute 32% to 45% of all neck pathologies in children [1]. The main complaint that made the family seek attention for the child may be the branchial anomaly. On admission, our patient voiced no other complaint other than branchial fistula. Observing similar branchial anomalies in the father alerted us to obtain more detailed information about the family history and proceeded with additional workup. We recognized that 8 of the 23 family members from 4 generations had a history of branchial anomalies and/or hearing loss. The family history in patients with BOR could lead to changes in life-style strategies by identifying the condition and preventing the potential severe long-term effects of BOR. Children with BOR may be born with kidney malformations that result in renal malfunction or failure as adults, and early detection and treatment of hearing impairment could improve the quality of life of these patients. Although the classic management of a branchial fistula does not necessarily require an extensive workup, BOR should be considered in patients with branchial fistula associated with external ear anomalies on physical examination and/or a history of hearing loss and similar findings in other family members.
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