Int Arch Otorhinolaryngol 2014; 18(01): 068-076
DOI: 10.1055/s-0033-1358659
Review Article
Thieme Publicações Ltda Rio de Janeiro, Brazil

Anatomical Changes and Audiological Profile in Branchio-oto-renal Syndrome: A Literature Review

Tâmara Andrade Lindau
1  Department of Speech Pathology, Universidade Estadual Paulista - UNESP, Marília, São Paulo, Brazil
,
Ana Cláudia Vieira Cardoso
1  Department of Speech Pathology, Universidade Estadual Paulista - UNESP, Marília, São Paulo, Brazil
,
Natalia Freitas Rossi
1  Department of Speech Pathology, Universidade Estadual Paulista - UNESP, Marília, São Paulo, Brazil
,
Célia Maria Giacheti
1  Department of Speech Pathology, Universidade Estadual Paulista - UNESP, Marília, São Paulo, Brazil
› Author Affiliations
Further Information

Address for correspondence

Célia Maria Giacheti, PhD
Department of Speech Pathology, Universidade Estadual Paulista UNESP
Av. Hygino Muzzi Filho, 737, Marília, São Paulo 14525-900
Brazil   

Publication History

27 August 2013

04 September 2013

Publication Date:
05 November 2013 (online)

 

Abstract

Introduction Branchio-oto-renal (BOR) syndrome is an autosomal-dominant genetic condition with high penetrance and variable expressivity, with an estimated prevalence of 1 in 40,000. Approximately 40% of the patients with the syndrome have mutations in the gene EYA1, located at chromosomal region 8q13.3, and 5% have mutations in the gene SIX5 in chromosome region 19q13. The phenotype of this syndrome is characterized by preauricular fistulas; structural malformations of the external, middle, and inner ears; branchial fistulas; renal disorders; cleft palate; and variable type and degree of hearing loss.

Aim Hearing loss is part of BOR syndrome phenotype. The aim of this study was to present a literature review on the anatomical aspects and audiological profile of BOR syndrome.

Data Synthesis Thirty-four studies were selected for analysis. Some aspects when specifying the phenotype of BOR syndrome are controversial, especially those issues related to the audiological profile in which there was variability on auditory standard, hearing loss progression, and type and degree of the hearing loss. Mixed loss was the most common type of hearing loss among the studies; however, there was no consensus among studies regarding the degree of the hearing loss.


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Introduction

The etiology of hearing loss has been investigated in molecular and genetics medical centers.[1] Anatomical and physiological changes in the auditory system have been described as part of the phenotype of numerous genetic syndromes, including the previously studied branchio-oto-renal (BOR) syndrome.[2]

The features of this clinical condition were first described in 1864 when Heusinger presented the initial reports on the association between branchial fistulas, preauricular fistulas, and hearing loss.[3] However, these features combined with auricular malformations and renal anomalies, thus comprising the phenotype of a specific condition, were described almost 110 years after the first clinical reports, and it was called BOR syndrome.[4] [5] [6]

Different classifications have been applied to this condition over the years, including Melnick-Fraser syndrome. This nomenclature originates from the first phenotype descriptions by these authors, “ear pits deafness syndrome”[7] and “branchio-oto-ureteral syndrome.”[8] However, contemporary studies have adopted the term “BOR syndrome” in a systematic way.

The clinical characteristics that compose the BOR syndrome phenotype can be classified according to the occurrence of larger and smaller anomalies. The larger or more frequent anomalies are: (1) hearing loss (sensorineural, conductive, or mixed), (2) preauricular pits, (3) renal anomalies ranging from mild hypoplasia to agenesis, (4) brachial fistulae, and (5) stenosis of the external auditory canal. The smaller or less frequent anomalies are: (1) lacrimal duct aplasia, (2) short or cleft palate, (3) retrognathia, (4) congenital hip dysplasia, (5) facial nerve paralysis, (6) gustatory lacrimation, and (7) pancreatic cyst.[9]

Such anomalies are used as criteria to diagnose BOR syndrome. In other words, the presence of three major deficiencies, or the combination of two major and two smaller anomalies, or the presence of a major anomaly associated with presence of another first degree family member diagnosed with the syndrome.[10]

One of the most mentioned characteristics as part of the BOR syndrome phenotype is progressive hearing loss, which can be mixed, conductive, or sensorineural and can range from mild to profound.[9] [11] In some patients, the hearing loss has a fluctuating pattern.[12] [13] [14] [15] Studies have reported the occurrence of congenital cholesteatoma among the less common characteristics.[16] [17] [18]

Genetic/Etiologic Bases of Branchio-Oto-Renal Syndrome

The estimated rate of BOR syndrome is 1:40,000.[4] [5] [6] [9] [19] BOR syndrome presents a pattern of autosomal-dominant inheritance and is considered the most common syndromic hearing loss form of genetic etiology with high penetrance and variable expressivity.[4] [8] [19] [20] [21] In addition to the autosomal-dominant, mitochondrial inheritance,[22] some patients present with “new” mutations.[7] [23] Deletions of various sizes have been found in individuals with BOR syndrome.[24] [25] [26]

The first chromosomal region associated with the syndrome was 8q12–22, identified from linkage studies in families that had multiple members affected.[27] Subsequently, the detailed genetic study of this region allowed researchers to determine the chromosomal region 8q13.3 was associated with the syndrome.[24] The EYA1 gene, which is responsible for the development of the branchial arches, auditory system, and kidneys, is located in this region.[25] [28]

EYA1 gene mutations have been reported in most cases of BOR syndrome.[2] [29] However, studies described that in many cases of clinically diagnosed BOR syndrome, the screening for alterations in the EYA1 gene was negative, which also showed that other genes are involved in the BOR syndrome etiology, indicating a condition with genetic heterogeneity.[10] [30] [31]

Missense mutations and small deletions in the SIX1 gene, located on chromosome region 14q23.1, were also reported by several studies that described families affected by BOR syndrome.[28] [32] [33] [34] [35] [36] However, intrafamilial phenotypic variability can be observed in all families studied that showed mutations in SIX1.[22]


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General Clinical Features of Branchio-Oto-Renal Syndrome

Based on the reviewed studies, the most common triad of BOR syndrome findings is: (1) hearing loss and preauricular fistulas located near the helix, (2) branchial fistulas typically found on the anterior border of the sternocleidomastoid muscle, and (3) a variability of renal anomalies, which often present no symptoms. Branchial fistulas are usually located next to the first branchial arch. However, a rare case was described where the subject had four branchial fistulas located at the first and second branchial arches.[37] [38]

A retrospective analysis of seven individuals diagnosed with BOR syndrome has shown that besides the applicant phenotype, other clinical features were found in these individuals, such as gustatory lacrimation, imperforate anus, otosclerosis, and congenital vocal cord paresis.[39]

The manifestations of BOR syndrome can also be composed of craniofacial abnormalities such as microcephaly,[39] hemifacial microsomy,[40] long face syndrome associated with lacrimal duct stenosis,[5] [7] [14] [17] [41] [42] overbite palate,[17] and retrognathia.[39] The presence of micrognathia,[43] hypodontia,[39] and microdontia associated with malformations of permanent molars[44] were also reported. Lacrimal duct stenosis, although rare, has been described in some studies,[6] [7] and its occurrence is associated with gustatory lacrimation.[39] [41]

One study described the presence of cardiac manifestation—mitral valve prolapse—in a family diagnosed with BOR syndrome (one family member had tachycardia). These symptoms were not reported in previous studies. This manifestation was identified in five of seven patients with BOR syndrome in this family, whereas hearing loss was present in all of them. Other previously described features such as branchial fistula, preauricular appendices, external ear malformation, renal anomalies, and anomalies of the lacrimal duct were found in this family.[45]

Limited kidney functions, bifid renal pelvis, hypoplasia, and renal cysts associated with urinary tract infections appeared in one study.[20] Another study reported that such infections and glomerulonephritis episodes may be associated with normal renal anatomy and physiology.[16] However, a case with a bifid kidney, double ureter, and vesicoureteric reflux[46] as well as two patients who reported congenital hydronephrosis were described.[40] Only one case has been described with severe reduction in kidney volume without family history of this condition,[47] and there was another case with renal agenesis.[48]

From 1975 to 2013, several authors have described specific phenotypes in individuals diagnosed with BOR syndrome: these articles are summarized in [Table 1]. Most of these studies describe isolated patients or a familial nucleus and show varied expressiveness.

Table 1

Description of general findings from BOR syndrome

  • Branchial anomalies

    • Branchial fistulae (first/second arches)

  • Other anomalies

    • Lacrimal duct aplasia/gustatory lacrimation

    • Palate abnormality (short/cleft)

    • Micrognathia/retrognathia

    • Facial asymmetry

    • Preauricular pits

    • Small ears and low implantation

    • Pinnae deformities

    • Facial nerve paresis

    • Microdontia/hypodontia

    • Congenital vocal cord paresis

    • Congenital hip dysplasia

    • Pancreatic duplication cyst

    • Mitral valve prolapse

  • Renal anomalies

    • Ureteral pelvic junction obstruction

    • Renal cyst

    • Renal agenesis

    • Renal hypoplasia

    • Renal aplasia

    • Double ureter

Abbreviation: BOR, branchio-oto-renal.


Hearing loss is part of the BOR syndrome phenotype. The aim of this study was to present a literature review on the anatomical aspects and audiological profile in this condition.


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Methods

This study review published studies describing BOR syndrome from 1975 to 2013. Research was performed on the following national and international databases: BIREME (Virtual Health Library—LILACS and IBECS) PubMed/MEDLINE (MEDlars onLINE), ProQuest, Web of Science (integrated into ISI Web of Knowledge), and OMIM (Online Mendelian Inheritance in Man).

The following research descriptors were used according to the criteria of the MeSH:

  1. “Branchio-Otorrenal Syndrome” and “Hearing Loss” or “Hearing Disorders”

  2. “Branchio-Oto-Renal Syndrome” and (“Hearing” or “Hearing Disorders” or “Hearing Loss”)

  3. “Branchio-Oto-Renal Syndrome”

Exclusion Criteria

This review refers to the auditory aspects of BOR syndrome and used the following criteria for the exclusion of articles: the title and summary were not related to the purpose of the review; repeated articles and articles written in languages other than English, Portuguese, or Spanish; animal studies; editorial letters, review articles, and articles in which BOR syndrome was associated with other syndromes or genetic conditions with partial phenotype of BOR syndrome; articles that cited BOR syndrome as a cause of loss of hearing; and those that were focused only on general and genetic aspects of BOR syndrome.

From the BIREME database (LILACS and IBECS) and ProQuest, six articles were found using research descriptor 1, and five articles were excluded based on the exclusion criteria. When searching the MEDLINE database, via PubMed, using research descriptor 2, 37 articles were found, 27 of which were excluded by the criteria mentioned above, and thus 10 articles remained. The last search was performed on the Web of Science database using research descriptor 3. It resulted in 96 articles, 73 of which were excluded considering the exclusion criteria, leaving 23 remaining articles.

The results concerning literature review and discussion followed the chronological order of publication, and the issues were grouped by the descriptors used in the literature.

[Fig. 1] shows the flow diagram that demonstrates the articles' selection criteria.

Zoom Image
Fig. 1 Flowchart demonstrating the process of deleting articles. Abbreviation: BOR, branchio-oto-renal syndrome.

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Literature Review

After the application of the exclusion criteria, 34 studies were selected and compiled on [Table 2], which contains the year of publication, article title, author, and number of the study participants.

Table 2

Summary of the reviewed articles' information

Article

Title

Author

Year

Sample

1

Familial branchio-oto-renal dysplasia: a new addition to the branchial arch syndromes.

Melnick et al[5]

1976

n = 4 (two generations)

2

Genetic aspects of the BOR syndrome—branchial fistulas, ear pits, hearing loss, and renal anomalies

Fraser et al[6]

1978

n = 8 (three generations)

3[a]

The earpits-deafness syndrome. Clinical and genetic aspects

Cremers, Fikkers-Van Noord[7]

1980

n = 19 (four families)

4

Temporal bone findings in a family with branchio-oto-renal syndrome (BOR)

Ostri et al[12]

1991

n = 19 (four generations)

5

Branchio-oto-renal (BOR) syndrome: variable expressivity in a five-generation pedigree

König et al[20]

1994

n = 6 (four generations)

6

Phenotypic manifestations of branchio-oto-renal syndrome

Chen et al[19]

1995

n = 32

7

Branchio-oto-renal syndrome

Millman et al[38]

1995

n = 1

8

Renal failure and deafness: branchio-oto-renal syndrome

Misra, Nolph[43]

1998

n = 1

9

Congenital cholesteatoma and malformations of the facial nerve: rare manifestations of the BOR syndrome

Graham et al[16]

1999

n = 2

10

New' manifestations of BOR syndrome

Weber, Kousseff[39]

1999

n = 7

11

Bilateral congenital cholesteatoma in branchio-oto-renal syndrome

Worley et al[17]

1999

n = 1

12

Branchio-oto-renal syndrome with generalized microdontia

Prabhu et al[44]

1999

n = 1

13

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family

Usami et al[54]

1999

n = 3 (two generations)

14

Temporal bone computed tomography findings in bilateral sensorineural hearing loss

Bamiou et al[55]

2000

n = 3

15

Branchio-oto-renal syndrome: a report on nine family groups

Bellini et al[42]

2001

n = 10 (nine families)

16

The presence of a widened vestibular aqueduct and progressive sensorineural hearing loss in the branchio-oto-renal syndrome. A family study

Stinckens et al[14]

2001

n = 12

17

Progressive fluctuant hearing loss, enlarged vestibular aqueduct, and cochlear hypoplasia in branchio-oto-renal syndrome

Kemperman et al[13]

2001

n = 2 (two generations)

18

Visualization of inner ear dysplasias in patients with sensorineural hearing loss

Klingebiel et al[57]

2001

n =  2

19

Inner ear anomalies are frequent but nonobligatory features of the branchio-oto-renal syndrome

Kemperman et al[58]

2002

n = 35 (six families)

20

A family with the branchio-oto-renal syndrome: clinical and genetic correlations

Pierides et al[46]

2002

n = 10 (two generations)

21

Temporal bone anomalies in the branchio-oto-renal syndrome: detailed computed tomographic and magnetic resonance imaging findings

Ceruti et al[15]

2002

n = 8 (four generations)

22

Síndrome branquio-oto-renal y colesteatoma congénito

Adiego et al[18]

2003

n = 1

23

Evidence of progression and fluctuation of hearing impairment in branchio-oto-renal syndrome

Kemperman et al[53]

2004

n = 32 (six families)

24

Temporal bone findings on computed tomography imaging in branchio-oto-renal syndrome

Propst et al[59]

2005

n = 21

25[a]

Non-inherited manifestation of bilateral branchial fistulae, bilateral pre-auricular sinuses and bilateral hearing loss: a variant of branchio-oto-renal syndrome

Rana et al[23]

2005

n = 1

26

Identification of a novel mutation in the EYA1 gene in a Korean family with branchio-oto-renal (BOR) syndrome

Kim et al[49]

2005

n = 2 (two generations)

27

Cochlear implantation in branchio-oto-renal syndrome—a surgical challenge

Kameswaran et al[56]

2007

n = 1

28

Branchio-oto-renal syndrome

Garg et al[47]

2008

n = 1

29

Achados genéticos, audiológicos e da linguagem oral de um núcleo familial com diagnóstico da síndrome Branquio-oto-renal (SBOR)

Furlan et al[51]

2008

n = 7 (two generations)

30

From a branchial fistula to a branchiootorenal syndrome: a case report and review of the literature

Senel et al[50]

2009

n = 1

31

Mitral valve prolapse as a new finding in branchio-oto-renal syndrome

Ayçiçek et al[45]

2010

n = 1

32

Diagnostic and surgical challenge: middle ear dermoid cyst in 12 month old with branchio-oto-renal syndrome and multiple middle-ear congenital anomalies

Johnston et al[40]

2011

n = 1

33

Young woman with branchio-oto-renal syndrome and a novel mutation in the EYA-1 gene

Nardi et al[48]

2011

n = 1

34

Congenital unilateral facial nerve palsy as an unusual presentation of BOR syndrome

Jankauskienè, Azukaitis[52]

2013

n = 1

a Syndrome manifestation as a noninherited characteristic.



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Results

Anatomical Changes and Audiological Profile

In the studies reviewed, a prevalence of mixed hearing loss was observed, followed by conductive and sensorineural hearing loss. Some studies reported that the presence of chronic or recurrent otitis media is an aggravating factor for hearing loss, which may be associated with ossicular chain malformations or alterations, or presence of cleft palate, increasing the number with conductive/mixed hearing loss.[6] [16] [20] [49] [50] [51] There was a higher recurrence of moderate and severe hearing loss among the studies' participants, probably due to the number of abnormalities found in the inner ear, which encompasses cochlear alterations to malformation of the vestibular system.

Some research verified that in addition to the auditory standards mentioned above, hearing loss could maintain a progressive and/or fluctuating pattern,[6] [13] [14] [15] [19] [46] [52] which contradicts other studies that related their standard as stable.[12] [16] [19] [53] A retrospective study identified significant hearing loss progression in 10 patients. The results demonstrated that in seven patients, the hearing loss was fluctuating; however, this fluctuation was only significant in young patients.[52] A study reported that patients with an enlarged endolymphatic sac or duct had hearing thresholds significantly higher than in those patients without such abnormalities,[52] which corroborates the study of Kemperman et al, 2001.[13]

In the literature, a description was found of three patients with BOR syndrome who also had cholesteatoma. In one of them, the cholesteatoma was in the temporal bone cavity, bilaterally, and showed no association with the facial nerve alterations. However, the other patients showed facial nerve alterations. One subject had facial nerve paralysis on the left side and in the other subject had right-side paralysis.[16] [17] [18] [54]

Cochlear implant in BOR syndrome was first used in a 3-year-old with congenital profound hearing loss and impaired language and speech development. Radiologic evaluation of the temporal bone and the inner ear showed severe dysplasia of the vestibule, ossicles, and bilaterally malformed semicircular canals and facial nerve posteriorly positioned. Three weeks after implantation, initial mapping showed positive responses. After hearing habilitation, the patient was able to recognize speech stimuli in a closed set.[55]

Radiologic studies and magnetic resonance imaging of the mastoid and middle ear showed several types of middle and inner ear pathology, among them: (1) hypoplasia, malformation and displacement of the ossicular chain, such as the junction of the hammer and anvil fixing the malleus in the tympanic membrane, and calcified oval window; (2) malformations—enlargement—and asymmetry of the semicircular canals/ducts and endolymphatic sac; and (3) cochlear hypoplasia or dysplasia.[6] [7] [14] [49] [50] [53] [56] [57] [58]

A study retrospectively assessed tomographic findings of 21 subjects (42 ears) with a clinical diagnosis of BOR syndrome, based on criteria derived from genotype and phenotype, and described the most common and easily identifiable features of BOR syndrome by visual inspection. The results of this assessment were: (1) apical cochlear hypoplasia was present in all individuals with BOR syndrome and no subject had normal hearing, (2) the facial nerve was diverted to the medial side of the cochlea in 38 of 42 ears, and (3) the inner ear channel was funnel-shaped in 36 of the 42 ears.[59]


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Discussion

The phenotypic features related to the most-mentioned anatomical ear alterations in BOR syndrome were: malformation; hyperplasia and low implantation of the ear; narrowing of the external acoustic meatus; ossicular chain abnormalities; reduced size of the middle ear cavity; otosclerosis; semicircular canal anomalies involving hypoplasia, dysplasia, and enlargement of the endolymphatic duct and sac; and cochlear hypoplasia.

The audiological profile, considering the type and degree of hearing loss and the association of the auditory system characteristics, is presented in [Table 3].

Table 3

Auditory system characteristics and description of hearing loss in BOR syndrome

Article

Type

Degree

Pattern

Anatomic changes: external, middle, and inner ear

Melnick et al[5]

Mixed

Mondini-type cochlear malformation and stapes fixation

Fraser et al[6]

Conductive/mixed

Mild to severe

Progressive

OC changes, ME fluid, otosclerosis

Cremers, Fikkers-Van Noord[7]

Conductive/mixed/sensorineural

Cochlear hypoplasia/dysplasia, narrow or wide internal auditory canal, OC anomalies, horizontal SC with reduced size

Ostri et al[12]

Mixed

Moderate to severe

Stable

Cochlear hypoplasia, SC hypoplasia and abnormal duct endolymphatic, massive OC and reduced size of ME

König et al[20]

Mixed

Severe

Malformation of OC

Chen et al[19]

Conductive/mixed/sensorineural

Mild to profound

Progressive/stable

Stenosis of the EEC, malformation of OC, cochlear hypoplasia/dysplasia and enlargement of the endolymphatic duct

Millman et al[38]

Severe

Misra, Nolph[43]

Mixed

Moderate to severe

Changes in OC

Graham et al[16]

Conductive

Moderate

Stable

Cholesteatoma, absence or abnormality of the ossicles and oval window, TM retraction

Weber, Kousseff[39]

Conductive/sensorineural

Mild to moderate

Otosclerosis

Worley et al[17]

Mixed

Moderate

Cholesteatoma, OC anomalies, otitis media—ventilation tubes

Prabhu et al[44]

Mixed

Malformed and hyperplastic right pinna and a preauricular pit on the left ear

Usami et al[54]

Conductive/mixed

Mild to moderate

Stable

Cochlear hypoplasia of the lateral and posterior semicircular canal, abnormal OC, soft mass density in the epitympanic and mastoid cavity

Bamiou et al[55]

Mondini-type cochlear malformation

Bellini et al[42]

Conductive/mixed/sensorineural

Stinckens et al[14]

Sensorineural

Progressive

Enlarged vestibular aqueduct, cochlear hypoplasia

Kemperman et al[13]

Sensorineural

Profound

Progressive/fluctuant

Cochlear hypoplasia, enlarged vestibular aqueduct

Klingebiel et al[57]

Dysplasia of the SC superior, cochlear hypoplasia (1.5 turn)

Kemperman et al[58]

Enlarged vestibular aqueduct, hypoplastic cochleae and labyrinths, malformed auricles

Pierides et al[46]

Progressive

Ceruti et al[15]

Sensorineural

Progressive

Cochlear hypoplasia/dysplasia, SC malformations, OC malformations

Adiego et al[18]

Mixed

Moderate

EEC stenosis, cholesteatoma, OC malformation, cochlear hypoplasia, abnormal morphology of the SC

Kemperman et al[53]

Progressive/fluctuant

Enlarged vestibular aqueduct, medial deviation of facial nerve, cochlear hypoplasia

Propst et al[59]

Cochlear hypoplasia, narrowed internal auditory canal

Rana et al[23]

Pneumatic temporal bone, partial agenesis of the EEC

Kim et al[49]

Mixed

Moderate to profound

EEC stenosis, dense mass in the mastoid and tympanic cavity, cochlear hypoplasia, enlarged vestibular aqueduct, OC malformation, otitis media

Kameswaran et al[56]

Sensorineural

Profound

Vestibular dysplasia, SC and ossicles malformation

Garg et al[47]

Moderate to profound

Furlan et al[51]

Conductive/mixed

Mild to moderate to severe

Senel et al[50]

Conductive/mixed

Mild to moderate

EEC stenosis, auricular malformation, cochlear and SC hypoplasia, OC malformation

Ayçiçek et al[45]

EE and IE malformation

Johnston et al[40]

Mixed

Moderate to severe

Cochlear hypoplasia, OC malformation, enlarged vestibular aqueduct

Nardi et al[48]

Enlarged vestibular aqueduct

Jankauskienè, Azukaitis[52]

Uncertain results of otoacoustic emission and facial nerve paralysis at the RE

Abbreviations: EE, external ear; EEC, external ear canal; IE, inner ear; ME, middle ear; OC, ossicular chain; RE, right ear; SC, semicircular canals; TM, tympanic membrane.


The analysis of these studies showed that there was a high frequency of mixed hearing loss (33.72%) followed by sensorineural (10.98%) and conductive hearing loss (7.84%); however, in 47.45% of the articles, this information was not present. The degree of hearing loss was classified as moderate in 12.94% of the articles, mild in 6.66%, severe in 6.27%, and profound in 4.73%. This information was not present in 67.84% of the articles. Only 29.4% of the studies described the hearing loss pattern, which was classified as stable, progressive, or fluctuating.


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Conclusion

Because hearing loss is mentioned in a great number of BOR syndrome studies. Deafness linked to preauricular fistula, branchial fistulae, and renal anomalies should be investigated and monitored by a multidisciplinary team, mainly otorhino-laryngologic professionals.

Due to the variable phenotypic expression described, many cases of BOR syndrome may have been underdiagnosed, and sometimes the diagnosis is delayed, even in cases where the hearing impairment is severe and interferes with the development of language and speech.

This review shows that some aspects remain controversial due to syndrome variability and the difficulty of early diagnosis, especially in issues related to the audiological profile where there is a great variability in the auditory pattern and the hearing loss progression, type, and degree. Most studies described that mixed hearing loss is the most common type; however, there is no consensus about the degree.

In the 40 years of research on BOR syndrome, studies were aimed at characterization of the phenotype of this syndrome, and the hearing loss was mentioned as part of the phenotype; however, few specific studies characterize the hearing loss standard, type, and degree.


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Address for correspondence

Célia Maria Giacheti, PhD
Department of Speech Pathology, Universidade Estadual Paulista UNESP
Av. Hygino Muzzi Filho, 737, Marília, São Paulo 14525-900
Brazil   


  
Zoom Image
Fig. 1 Flowchart demonstrating the process of deleting articles. Abbreviation: BOR, branchio-oto-renal syndrome.