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Branchiootic syndrome—a clinical case report and review of the literature
Journal of Pediatric Surgery (2012) 47, 1604–1606
www.elsevier.com/locate/jpedsurg
Branchiootic syndrome—a clinical case report and review of the literature Imad Amer ⁎, Adam Falzon, Natasha Choudhury, Khalid Ghufoor Department of Paediatric ENT, Royal London Hospital, London, United Kingdom Received 31 December 2011; revised 2 May 2012; accepted 3 May 2012
Key words: Branchio-otorenal; Branchial fistula; Second branchial arch anomaly
Abstract Branchiootoic syndrome is part of the spectrum of brachiootorenal disorders. Brachiootorenal disorder is a rare autosomal dominant condition, characterized by malformations of the outer, middle, and inner ear, which are associated with branchial and renal anomalies. We describe a case of bilateral branchiootoic syndrome and discuss the anatomy of second branchial cleft fistulae and the surgical management of this uncommon condition. We report the case of a 6-year-old girl referred to our department with bilateral intermittently discharging neck swellings. Clinical examination revealed bilateral branchial fistulae and preauricular sinuses, on a background of a positive family history of branchial fistulae. A magnetic resonance imaging scan confirmed the diagnosis of bilateral second branchial cleft fistulae. In view of her symptoms, she underwent bilateral branchial fistula excision and tonsillectomy with an uneventful postoperative recovery. © 2012 Elsevier Inc. All rights reserved.
Branchiootorenal syndrome (BOR) is a rare autosomal dominant condition with 1 incidence in 40,000, characterized by malformations of the outer, middle, and inner ear and branchial and renal malformations [1]. An association between preauricular pits, hearing impairment, and branchial fistulae was first recognized by Heusinger in 1864 [2]; however, BOR was not comprehensively described as a discreet entity until the late 1970s, following further descriptions by Melnick et al [3] and Fraser et al [4]. Conversely, branchiootoic syndrome (BOS) is used to describe affected individuals who demonstrate the aforementioned otoic and branchial anomalies without the associated renal findings [1]. There is recent emerging literature regarding the genetic basis for these conditions. There are 3 reported genetic ⁎ Corresponding author. Tel.: +44 7980895830. E-mail address: [email protected] (I. Amer). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2012.05.016
mutations that are associated with BOR [5]. These include mutations of the EYA1, SIX1, and SIX5 genes. The most commonly associated genetic mutation is in the EYA1 gene, which is thought to occur in approximately 40% of people with this condition. EYA1 and SIX1 mutations have also been found in some people with BOS [5]. The incidence of this condition has been estimated to be 1:40,000 and has been reported in 2% of profoundly deaf children [6], thus making BOR one of the more common causes of autosomal dominant syndromic hearing impairment [7]. The surgical management of branchial arch anomalies requires a thorough understanding of their embryological origin and should include careful perioperative anatomical delineation with imaging, before surgical intervention is considered. Surgical excision should include dissection of the full length of the tract with tonsillectomy, in cases where the tract is confirmed to be extending into the ipsilateral tonsillar fossa.
Branchiootic syndrome
1605
1. Case report Recurrent bilateral neck swellings associated with intermittent discharge prompted the referral of a 6-year-old girl to our department. The child was otherwise well, with no other known comorbidities and reported no other ear, nose, and throat symptoms. During the consultation, the child's mother reported having had similar problems in her adolescent years, requiring surgical intervention later for a unilateral second branchial arch fistula. On examination, the child was noted to have bilateral palpable cysts with nondischarging pits along the anterior border of the sternocleidomastoid muscle at the junction of the middle and lower thirds as well as bilateral preauricular sinuses. A clinical diagnosis of bilateral branchial fistulae was made; this was supported by a magnetic resonance imaging (MRI) scan (Fig. 1). A renal ultrasound confirmed no associated renal malformations, thus confirming a diagnosis of BOS. In view of her recurrent symptoms, the child underwent bilateral branchial fistulae excision and tonsillectomy.
Branchial Cyst
Branchial fistula Fig. 2 Left brachial sinus, including cystic component, dissected via an elliptical incision in the neck.
taining the integrity of the tract medial to the tonsil. This was then delivered in its entirety via the oral cavity (see Figs. 3 and 4). The child made an uneventful postoperative recovery.
3. Discussion 2. Surgical approach The surgical approach began with delineation of the tracts by gentle cannulation of their external openings with a 20Gauge cannula, through which the tracts were infiltrated with blue methlyene dye to facilitate visualization of their full length up to their internal opening (fistulagram). An elliptical incision was made, centered around the skin of the pits on the anterior neck and the tract carefully dissected toward the carotid bifurcation (Fig. 2). Care was taken to identify and preserve the hypoglossal and glossopharyngeal nerve, which were in close proximity to the tract. On approaching the superomedial extent of the tract, tonsillectomy was performed while carefully main-
We describe a case of a young child seen in our department with bilateral branchial fistulae, which was confirmed on MRI to be second branchial cleft fistulae, associated with preauricular sinuses. Further investigation excluded any renal impairment, and therefore, a diagnosis of BOS was made. In view of her ongoing symptoms, she underwent bilateral branchial fistula excision and tonsillectomy. Branchiootoic syndrome represents part of the spectrum of BOR, where outer, middle, or inner ear anomalies and branchial anomalies are not associated with renal malformations. Complete fistulae with both an internal and an external opening are rare; a retrospective study by Ford et al [8], which evaluated a series of 106 patients with branchial arch anomalies, noted only 2 complete fistulae.
Branchial Cyst
Right Branchial
tonsil
Cyst Branchial fistula
Fig. 1 Magnetic resonance imaging delineating the presence of cystic components bilaterally (arrows).
Fig. 3 Right side brachial sinus being delivered intact transorally after tonsillectomy.
1606
I. Amer et al. Branchial Cyst
External
Left tonsil
sinus
Right tonsil
Branchial Cyst
Branchial fistula
Cystic component
Fig. 4 Intact left branchial fistula with intact branchial cyst and tract.
The clinical presentation in individuals affected by BOR is very variable because penetrance is high but incomplete, demonstrating variable expressivity between and within affected families [9]. The BOR phenotype is typically described to include cup-shaped pinnae, preauricular pits, branchial fistulae, and mild renal anomalies. However, preauricular tags; lacrimal duct stenosis; renal aplasia or agenesis; a constricted palate; a deep overbite; and a long, narrow face have also been described in these patients [7]. Variation in the clinical features of BOR makes it a very heterogeneous disease. Therefore, in 2004, Chang et al [10] described “major” and “minor” phenotype characteristics. They included branchial anomalies, deafness, preauricular pits, and renal anomalies as major criteria and external ear anomalies, middle ear anomalies, inner ear anomalies, preauricular tags, facial asymmetry, and palate abnormalities as minor criteria. Furthermore, they defined the clinical criteria of BOR to include affected individuals as having at least 3 major criteria, 2 major and 2 minor criteria, or 1 major criterion and affected first-degree relative with BOR [10]. An appreciation of the related embryology is crucial to understanding the surgical management and associated risks. The branchial arches, branchial clefts, and pharyngeal pouches are structures that begin to develop in the fourth week of embryonic development. These complexes represent condensations of endodermal, mesodermal, and ectodermal tissue in the primitive pharynx, and hence, each arch gives rise to a cartilaginous core, a muscular component, an artery, and a cranial nerve. The bony elements that develop from the second arch include the lesser cornu and body of the hyoid
bone (as well as the stapes, styloid process, and stylohyoid ligament). The second pharyngeal pouch in turn develops into the tonsil. Thus, anatomically, the typical second branchial fistula has its external opening at the anterior border of the junction of the middle and lower thirds of the sternocleidomastoid muscle. The tract typically pierces the platysma and ascends along the carotid sheath, passing through the carotid bifurcation (lying superficial to the internal carotid artery) and crosses over the hypoglossal and glossopharyngeal nerves. The tract then characteristically extends superiorly, ending in the upper half of the posterior faucial pillar, the supratonsillar fossa, or directly onto the tonsillar surface. The surgical management of branchial arch anomalies requires a thorough understanding of their embryological origin and should include careful perioperative anatomical delineation with computed tomography, fistulagram or MRI, or a combination of these, before surgical intervention is considered. An intraoperative fistulagram may facilitate the dissection. Surgical excision should include dissection of the full length of the tract with tonsillectomy.
References [1] Senel E, Kocak H, Akbiyik F, et al. From a branchial fistula to a branchiootorenal syndrome: a case report and review of the literature. J Pediatr Surg 2009 Mar;44(3):623-5. [2] Heusinger CF. Hals-Kiemen-Fisteln von noch nicht beobachteter form Virchows. Arch Path Anat 1864;29:338-80. [3] Melnick M, Bixler D, Silk K, et al. Autosomal dominant branchiootorenal dysplasia. Birth Defects Orig Artic Ser 1975;11:121-8. [4] Fraser FC, Ling D, Clogg D, et al. Genetic aspects of the BOR syndrome-branchial fistulas, ear pits, hearing loss, and renal anomalies. Am J Med Genet 1978;2:241-52. [5] Stratakis CA, Lin J-P, Rennert OM. Description of large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss and ear pits and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3). Am J Med Genet 1998;79:209-14. [6] Fraser FC, Sproule JR, Halal F. Frequency of the branchio-oto-renal (BOR) syndrome in children with profound hearing loss. Am J Med Genet 1980;7:341-9. [7] Kochhar A, Fischer SM, Kimberling WJ, et al. Branchio-oto-renal syndrome. Am J Med Genet 2007;15(143A(14)):1671-8. [8] Ford GR, Balakrishnan A, Evans JNG, et al. Branchial cleft and pouch anomalies. J Laryngol Otol 1992;106:137-43. [9] Konig R, Fuchs S, Dukiet C. Branchio-oto-renal (BOR) syndrome: variable expressivity in a five-generation pedigree. Eur J Pediatr 1994;153:446-50. [10] Chang EH, Menezes M, Meyer NC, et al. Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum Mutat 2004;6:582-9.
www.elsevier.com/locate/jpedsurg
Branchiootic syndrome—a clinical case report and review of the literature Imad Amer ⁎, Adam Falzon, Natasha Choudhury, Khalid Ghufoor Department of Paediatric ENT, Royal London Hospital, London, United Kingdom Received 31 December 2011; revised 2 May 2012; accepted 3 May 2012
Key words: Branchio-otorenal; Branchial fistula; Second branchial arch anomaly
Abstract Branchiootoic syndrome is part of the spectrum of brachiootorenal disorders. Brachiootorenal disorder is a rare autosomal dominant condition, characterized by malformations of the outer, middle, and inner ear, which are associated with branchial and renal anomalies. We describe a case of bilateral branchiootoic syndrome and discuss the anatomy of second branchial cleft fistulae and the surgical management of this uncommon condition. We report the case of a 6-year-old girl referred to our department with bilateral intermittently discharging neck swellings. Clinical examination revealed bilateral branchial fistulae and preauricular sinuses, on a background of a positive family history of branchial fistulae. A magnetic resonance imaging scan confirmed the diagnosis of bilateral second branchial cleft fistulae. In view of her symptoms, she underwent bilateral branchial fistula excision and tonsillectomy with an uneventful postoperative recovery. © 2012 Elsevier Inc. All rights reserved.
Branchiootorenal syndrome (BOR) is a rare autosomal dominant condition with 1 incidence in 40,000, characterized by malformations of the outer, middle, and inner ear and branchial and renal malformations [1]. An association between preauricular pits, hearing impairment, and branchial fistulae was first recognized by Heusinger in 1864 [2]; however, BOR was not comprehensively described as a discreet entity until the late 1970s, following further descriptions by Melnick et al [3] and Fraser et al [4]. Conversely, branchiootoic syndrome (BOS) is used to describe affected individuals who demonstrate the aforementioned otoic and branchial anomalies without the associated renal findings [1]. There is recent emerging literature regarding the genetic basis for these conditions. There are 3 reported genetic ⁎ Corresponding author. Tel.: +44 7980895830. E-mail address: [email protected] (I. Amer). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2012.05.016
mutations that are associated with BOR [5]. These include mutations of the EYA1, SIX1, and SIX5 genes. The most commonly associated genetic mutation is in the EYA1 gene, which is thought to occur in approximately 40% of people with this condition. EYA1 and SIX1 mutations have also been found in some people with BOS [5]. The incidence of this condition has been estimated to be 1:40,000 and has been reported in 2% of profoundly deaf children [6], thus making BOR one of the more common causes of autosomal dominant syndromic hearing impairment [7]. The surgical management of branchial arch anomalies requires a thorough understanding of their embryological origin and should include careful perioperative anatomical delineation with imaging, before surgical intervention is considered. Surgical excision should include dissection of the full length of the tract with tonsillectomy, in cases where the tract is confirmed to be extending into the ipsilateral tonsillar fossa.
Branchiootic syndrome
1605
1. Case report Recurrent bilateral neck swellings associated with intermittent discharge prompted the referral of a 6-year-old girl to our department. The child was otherwise well, with no other known comorbidities and reported no other ear, nose, and throat symptoms. During the consultation, the child's mother reported having had similar problems in her adolescent years, requiring surgical intervention later for a unilateral second branchial arch fistula. On examination, the child was noted to have bilateral palpable cysts with nondischarging pits along the anterior border of the sternocleidomastoid muscle at the junction of the middle and lower thirds as well as bilateral preauricular sinuses. A clinical diagnosis of bilateral branchial fistulae was made; this was supported by a magnetic resonance imaging (MRI) scan (Fig. 1). A renal ultrasound confirmed no associated renal malformations, thus confirming a diagnosis of BOS. In view of her recurrent symptoms, the child underwent bilateral branchial fistulae excision and tonsillectomy.
Branchial Cyst
Branchial fistula Fig. 2 Left brachial sinus, including cystic component, dissected via an elliptical incision in the neck.
taining the integrity of the tract medial to the tonsil. This was then delivered in its entirety via the oral cavity (see Figs. 3 and 4). The child made an uneventful postoperative recovery.
3. Discussion 2. Surgical approach The surgical approach began with delineation of the tracts by gentle cannulation of their external openings with a 20Gauge cannula, through which the tracts were infiltrated with blue methlyene dye to facilitate visualization of their full length up to their internal opening (fistulagram). An elliptical incision was made, centered around the skin of the pits on the anterior neck and the tract carefully dissected toward the carotid bifurcation (Fig. 2). Care was taken to identify and preserve the hypoglossal and glossopharyngeal nerve, which were in close proximity to the tract. On approaching the superomedial extent of the tract, tonsillectomy was performed while carefully main-
We describe a case of a young child seen in our department with bilateral branchial fistulae, which was confirmed on MRI to be second branchial cleft fistulae, associated with preauricular sinuses. Further investigation excluded any renal impairment, and therefore, a diagnosis of BOS was made. In view of her ongoing symptoms, she underwent bilateral branchial fistula excision and tonsillectomy. Branchiootoic syndrome represents part of the spectrum of BOR, where outer, middle, or inner ear anomalies and branchial anomalies are not associated with renal malformations. Complete fistulae with both an internal and an external opening are rare; a retrospective study by Ford et al [8], which evaluated a series of 106 patients with branchial arch anomalies, noted only 2 complete fistulae.
Branchial Cyst
Right Branchial
tonsil
Cyst Branchial fistula
Fig. 1 Magnetic resonance imaging delineating the presence of cystic components bilaterally (arrows).
Fig. 3 Right side brachial sinus being delivered intact transorally after tonsillectomy.
1606
I. Amer et al. Branchial Cyst
External
Left tonsil
sinus
Right tonsil
Branchial Cyst
Branchial fistula
Cystic component
Fig. 4 Intact left branchial fistula with intact branchial cyst and tract.
The clinical presentation in individuals affected by BOR is very variable because penetrance is high but incomplete, demonstrating variable expressivity between and within affected families [9]. The BOR phenotype is typically described to include cup-shaped pinnae, preauricular pits, branchial fistulae, and mild renal anomalies. However, preauricular tags; lacrimal duct stenosis; renal aplasia or agenesis; a constricted palate; a deep overbite; and a long, narrow face have also been described in these patients [7]. Variation in the clinical features of BOR makes it a very heterogeneous disease. Therefore, in 2004, Chang et al [10] described “major” and “minor” phenotype characteristics. They included branchial anomalies, deafness, preauricular pits, and renal anomalies as major criteria and external ear anomalies, middle ear anomalies, inner ear anomalies, preauricular tags, facial asymmetry, and palate abnormalities as minor criteria. Furthermore, they defined the clinical criteria of BOR to include affected individuals as having at least 3 major criteria, 2 major and 2 minor criteria, or 1 major criterion and affected first-degree relative with BOR [10]. An appreciation of the related embryology is crucial to understanding the surgical management and associated risks. The branchial arches, branchial clefts, and pharyngeal pouches are structures that begin to develop in the fourth week of embryonic development. These complexes represent condensations of endodermal, mesodermal, and ectodermal tissue in the primitive pharynx, and hence, each arch gives rise to a cartilaginous core, a muscular component, an artery, and a cranial nerve. The bony elements that develop from the second arch include the lesser cornu and body of the hyoid
bone (as well as the stapes, styloid process, and stylohyoid ligament). The second pharyngeal pouch in turn develops into the tonsil. Thus, anatomically, the typical second branchial fistula has its external opening at the anterior border of the junction of the middle and lower thirds of the sternocleidomastoid muscle. The tract typically pierces the platysma and ascends along the carotid sheath, passing through the carotid bifurcation (lying superficial to the internal carotid artery) and crosses over the hypoglossal and glossopharyngeal nerves. The tract then characteristically extends superiorly, ending in the upper half of the posterior faucial pillar, the supratonsillar fossa, or directly onto the tonsillar surface. The surgical management of branchial arch anomalies requires a thorough understanding of their embryological origin and should include careful perioperative anatomical delineation with computed tomography, fistulagram or MRI, or a combination of these, before surgical intervention is considered. An intraoperative fistulagram may facilitate the dissection. Surgical excision should include dissection of the full length of the tract with tonsillectomy.
References [1] Senel E, Kocak H, Akbiyik F, et al. From a branchial fistula to a branchiootorenal syndrome: a case report and review of the literature. J Pediatr Surg 2009 Mar;44(3):623-5. [2] Heusinger CF. Hals-Kiemen-Fisteln von noch nicht beobachteter form Virchows. Arch Path Anat 1864;29:338-80. [3] Melnick M, Bixler D, Silk K, et al. Autosomal dominant branchiootorenal dysplasia. Birth Defects Orig Artic Ser 1975;11:121-8. [4] Fraser FC, Ling D, Clogg D, et al. Genetic aspects of the BOR syndrome-branchial fistulas, ear pits, hearing loss, and renal anomalies. Am J Med Genet 1978;2:241-52. [5] Stratakis CA, Lin J-P, Rennert OM. Description of large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss and ear pits and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3). Am J Med Genet 1998;79:209-14. [6] Fraser FC, Sproule JR, Halal F. Frequency of the branchio-oto-renal (BOR) syndrome in children with profound hearing loss. Am J Med Genet 1980;7:341-9. [7] Kochhar A, Fischer SM, Kimberling WJ, et al. Branchio-oto-renal syndrome. Am J Med Genet 2007;15(143A(14)):1671-8. [8] Ford GR, Balakrishnan A, Evans JNG, et al. Branchial cleft and pouch anomalies. J Laryngol Otol 1992;106:137-43. [9] Konig R, Fuchs S, Dukiet C. Branchio-oto-renal (BOR) syndrome: variable expressivity in a five-generation pedigree. Eur J Pediatr 1994;153:446-50. [10] Chang EH, Menezes M, Meyer NC, et al. Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum Mutat 2004;6:582-9.