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Branchio-oculo-facial syndrome with the atresia of external ear
International Journal of Pediatric Otorhinolaryngology (2005) 69, 1575—1578
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CASE REPORT
Branchio-oculo-facial syndrome with the atresia of external ear Ozcan Ozturk *, Abdurrahman Tokmak, Levent Demirci, Fatma Silan, Ender Guclu Department of Otorhinolaryngology, Duzce Medical Faculty, 81010 Duzce, Turkey Received 23 February 2005; accepted 14 April 2005
KEYWORDS Branchio-oculo-facial syndrome; External ear atresia; Preauricular pit; Maxillar hypoplasia; Mandibular hypoplasia
Summary We report an 8-year-old child with branchio-oculo-facial syndrome. He showed atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, mild ptosis on the left side, lacrimal duct obstruction, unilateral branchial cyst, hypertrichosis of the neck, left foot showed mild syndactily of fourth and fifth toes and dental abnormalities. His mother had pseudocleft of the lip which led to the diagnosis. The importance of serial observations in patients with rare genetic disorders is emphasized. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Previous reports branchio-oculo-facial syndrome (BOFS) have delineated a newly recognized autosomal dominant branchio-oculo-facial syndrome of pseudocleft of the lip, lacrimal duct obstruction, malformations of the ear and nose, linear skin lesions behind the ears, and variable presence of coloboma, microphtalmia, upslanting palpebral fissures, auricular pits, lip pits, high-arched palate, dental anomalies, sebaceos cysts of the scalp, premature greying of the hair in adults, hand anomalies, growth retardation, and developmental delay [1—4]. Extracraniofacial malformations are uncommon. Neurodevelopment is usually normal although * Corresponding author. Tel.: +90 5325988086; fax: +90 3805414105. E-mail address: [email protected] (O. Ozturk).
retardation may occur. Autosomal dominant inheritance due to a single mutant gene is the likely etiology suggested by several instances of vertical transmission, including male-to-male transmission. No reported BOFS patients have had a chromosome abnormality [5—7].
2. Clinical report The patient is a 8-year-old boy born as the second child of a 32-year-old mother and 36-year-old father. The parents are not consangineous. Pregnancy and terme delivery were normal. Birth parameters were normal: weight was 4.400 kg and length was 50 cm. The first child is a 11-year-old girl and the third child is a 2.5-year-old boy. These children were normal. He showed atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, dental abnormalities, mild ptosis on the left
0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.04.013
1576
Fig. 1 Atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, mild ptosis on the left side.
side, lacrimal duct obstruction, unilateral branchial cyst, left foot showed mild partial syndactily of fourth and fifth toes, hypertrichosis of the neck (Figs. 1 and 2). Computed tomographic scans of the temporal bones showed aetresia of the external ear, tympanic cavity was not present, ossicular chain was not intakt and the pneumatization of the middle ear and mastoid bones was absent (Fig. 3). We observed normal inner ears and normal bilateral internal auditory canals. The patient had only bone conduction at the left ear. Hearing threshold of the right ear was within normal limits (Figs. 4 and 5). Skeletal X-ray films, kidney ultrasonography and haematoligical parameters were normal. Chromosomal examination on a peripheral blood lymphocyte culture revealed a 46, Y, normal male karyotype. His psychomotor development was borderline. His family members were also examined and his mother had a pseudocleft of the lip (Fig. 6).
O. Ozturk et al.
Fig. 2
Hypertrichosis of the neck.
monic anomalies in the branchio-oculo-facial syndrome [6]. Supra-auricular skin defects are less common and mentioned to be present in 14% of the patients. Craniofacial findings in BOFS patients are variable and include broad nasal bridge, flattened nasal tip, sparse hair with premature graying, cleft lip the presence of a pseudocleft (54%). Also, the
3. Discussion Postauricular and cervical skin defects with or without sinus fistule have been reported as pathogno-
Fig. 3 The view of computed tomographic scan of the temporal bone.
Branchio-oculo-facial syndrome with the atresia of external ear
Fig. 4
Fig. 5
1577
Normal odiologic diagram of the right ear.
Odiologic diagram shows no air conduction on the left ear.
ophtalmological symptoms are variable: nasolacrimal duct stenosis (74%), coloboma of the iris (46%) and micro-anophthalmia (62%). External ear abnormalities with low-set posteriorly rotated pinnae are found in 91%. Hearing loss is documented in 37% of the patients [6]. Renal abnormalies and CNS malformations are rare. Intelligence is usually normal, although mild (33%) to severe (8%) mental retardation may occur [6]. Some similarities with branchio-oto-renal (BOR) syndrome and branchio-oculo-facial syndrome have been observed. Both syndromes may have nasolacrimal duct stenosis, deafness, malformed pinnae, prehelical pits, renal anomalies, or development delays [6]. Despite this apparent overlap, there is little real phenotypic overlap. These conditions should not be confused. Unlike BOF syndrome, patients with BOR syndrome do not have the unusual erythematous, thin wrinkled skin defect of the neck or supra-infra-auricular area, cleft lip or pseudocleft and microphthalmia.
Legius et al. reported a family in which father and son had manifestations of both branchiooto-renal and BOF syndromes. They suggested that both syndromes might be due to a single gene with variable expression [8,9]. However, lip pseudocleft and haemangiomatous fistulae without kidney anomalies are peculiar to the BOF syndrome. After evaluating the available findings we suspected a bronchio-otofacial syndrome. The findings of the patient was consistent with both BOR and BOF syndromes. His family members were also examined and his mother had a pseudocleft of the lip. So, BOR syndrome was excluded and the diagnosis was established as BOF syndrome. In syndromic cases, some findings may be present in a family member and not in patient him/herself. The finding of a pseudocleft of the upper lip in our patient’s mother lead to the diagnosis. We believe that examination of the family members is essential to avoid a misdiagnosis.
1578
O. Ozturk et al.
References
Fig. 6
Patient’s mother with a pseudocleft of the lip.
[1] W.K. Lee, A.W. Root, N. Fenske, Bilateral branchial cleft sinuses associated with intrauterine and postnatal growth retardation, premature aging and unusual facial appearances: a new syndrome with dominant transmission, Am. J. Med. Genet. 11 (1982) 345—352. [2] B.D. Hall, A. de Lorimer, L.H. Foster, A new syndrome of hemangiomatous branchial clefts, lip pseudoclefts, and unusual facial appearance, Am. J. Med. Genet. 14 (1983) 135— 138. [3] A. Fujimato, M. Lipson, R.V. Lacro, N.W. Shinno, W.D. Boelter, R.L. Jones, New automosal dominant branchio-oculo-facial syndrome, Am. J. Med. Genet. 27 (1987) 943—951. [4] S. Schmerler, T. Kushnick, F. Desposito, Long term evaluation of a child with the branchio-oculo-facial syndrome, Am. J. Med. Genet. 44 (1992) 177—178. [5] A.E. Lin, H.W. Losken, R. Jaffe, A.W. Biglan, The branchiooculo-facial syndrome, Cleft Palate Craniofac. J. 28 (1991) 96—102. [6] A.E. Lin, R.J. Gorlin, I.W. Lurie, H.G. Brunner, I. Van der Burgt, I.V. Naumchik, Further delination of the branchiooculo-facial syndrome, Am. J. Med. Genet. 56 (1995) 42—59. [7] A.E. Lin, E.V. Semina, S.D. Hirsch, E.R. Roeder, C.J.R. Curry, K. Rosenbaum, Exclusion of the branchio-oto-renal syndrome locus (EYA1) from patients with branchio-oculo-facial syndrome, Am. J. Med. Genet. 91 (2000) 387—390. [8] E. Legius, J.P. Fryns, Branchio-oculo-facial and branchio-otorenal syndromes are distinct entities, Clin. Genet. 41 (1992) 223. [9] E. Legius, J.P. Fryns, I. Van der Burgt, Dominant branchial cleft syndrome with characteristics of both branchio-otorenal and branchio-oculo-facial syndrome, Clin. Genet. 37 (1990) 347—350.
www.elsevier.com/locate/ijporl
CASE REPORT
Branchio-oculo-facial syndrome with the atresia of external ear Ozcan Ozturk *, Abdurrahman Tokmak, Levent Demirci, Fatma Silan, Ender Guclu Department of Otorhinolaryngology, Duzce Medical Faculty, 81010 Duzce, Turkey Received 23 February 2005; accepted 14 April 2005
KEYWORDS Branchio-oculo-facial syndrome; External ear atresia; Preauricular pit; Maxillar hypoplasia; Mandibular hypoplasia
Summary We report an 8-year-old child with branchio-oculo-facial syndrome. He showed atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, mild ptosis on the left side, lacrimal duct obstruction, unilateral branchial cyst, hypertrichosis of the neck, left foot showed mild syndactily of fourth and fifth toes and dental abnormalities. His mother had pseudocleft of the lip which led to the diagnosis. The importance of serial observations in patients with rare genetic disorders is emphasized. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Previous reports branchio-oculo-facial syndrome (BOFS) have delineated a newly recognized autosomal dominant branchio-oculo-facial syndrome of pseudocleft of the lip, lacrimal duct obstruction, malformations of the ear and nose, linear skin lesions behind the ears, and variable presence of coloboma, microphtalmia, upslanting palpebral fissures, auricular pits, lip pits, high-arched palate, dental anomalies, sebaceos cysts of the scalp, premature greying of the hair in adults, hand anomalies, growth retardation, and developmental delay [1—4]. Extracraniofacial malformations are uncommon. Neurodevelopment is usually normal although * Corresponding author. Tel.: +90 5325988086; fax: +90 3805414105. E-mail address: [email protected] (O. Ozturk).
retardation may occur. Autosomal dominant inheritance due to a single mutant gene is the likely etiology suggested by several instances of vertical transmission, including male-to-male transmission. No reported BOFS patients have had a chromosome abnormality [5—7].
2. Clinical report The patient is a 8-year-old boy born as the second child of a 32-year-old mother and 36-year-old father. The parents are not consangineous. Pregnancy and terme delivery were normal. Birth parameters were normal: weight was 4.400 kg and length was 50 cm. The first child is a 11-year-old girl and the third child is a 2.5-year-old boy. These children were normal. He showed atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, dental abnormalities, mild ptosis on the left
0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.04.013
1576
Fig. 1 Atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, mild ptosis on the left side.
side, lacrimal duct obstruction, unilateral branchial cyst, left foot showed mild partial syndactily of fourth and fifth toes, hypertrichosis of the neck (Figs. 1 and 2). Computed tomographic scans of the temporal bones showed aetresia of the external ear, tympanic cavity was not present, ossicular chain was not intakt and the pneumatization of the middle ear and mastoid bones was absent (Fig. 3). We observed normal inner ears and normal bilateral internal auditory canals. The patient had only bone conduction at the left ear. Hearing threshold of the right ear was within normal limits (Figs. 4 and 5). Skeletal X-ray films, kidney ultrasonography and haematoligical parameters were normal. Chromosomal examination on a peripheral blood lymphocyte culture revealed a 46, Y, normal male karyotype. His psychomotor development was borderline. His family members were also examined and his mother had a pseudocleft of the lip (Fig. 6).
O. Ozturk et al.
Fig. 2
Hypertrichosis of the neck.
monic anomalies in the branchio-oculo-facial syndrome [6]. Supra-auricular skin defects are less common and mentioned to be present in 14% of the patients. Craniofacial findings in BOFS patients are variable and include broad nasal bridge, flattened nasal tip, sparse hair with premature graying, cleft lip the presence of a pseudocleft (54%). Also, the
3. Discussion Postauricular and cervical skin defects with or without sinus fistule have been reported as pathogno-
Fig. 3 The view of computed tomographic scan of the temporal bone.
Branchio-oculo-facial syndrome with the atresia of external ear
Fig. 4
Fig. 5
1577
Normal odiologic diagram of the right ear.
Odiologic diagram shows no air conduction on the left ear.
ophtalmological symptoms are variable: nasolacrimal duct stenosis (74%), coloboma of the iris (46%) and micro-anophthalmia (62%). External ear abnormalities with low-set posteriorly rotated pinnae are found in 91%. Hearing loss is documented in 37% of the patients [6]. Renal abnormalies and CNS malformations are rare. Intelligence is usually normal, although mild (33%) to severe (8%) mental retardation may occur [6]. Some similarities with branchio-oto-renal (BOR) syndrome and branchio-oculo-facial syndrome have been observed. Both syndromes may have nasolacrimal duct stenosis, deafness, malformed pinnae, prehelical pits, renal anomalies, or development delays [6]. Despite this apparent overlap, there is little real phenotypic overlap. These conditions should not be confused. Unlike BOF syndrome, patients with BOR syndrome do not have the unusual erythematous, thin wrinkled skin defect of the neck or supra-infra-auricular area, cleft lip or pseudocleft and microphthalmia.
Legius et al. reported a family in which father and son had manifestations of both branchiooto-renal and BOF syndromes. They suggested that both syndromes might be due to a single gene with variable expression [8,9]. However, lip pseudocleft and haemangiomatous fistulae without kidney anomalies are peculiar to the BOF syndrome. After evaluating the available findings we suspected a bronchio-otofacial syndrome. The findings of the patient was consistent with both BOR and BOF syndromes. His family members were also examined and his mother had a pseudocleft of the lip. So, BOR syndrome was excluded and the diagnosis was established as BOF syndrome. In syndromic cases, some findings may be present in a family member and not in patient him/herself. The finding of a pseudocleft of the upper lip in our patient’s mother lead to the diagnosis. We believe that examination of the family members is essential to avoid a misdiagnosis.
1578
O. Ozturk et al.
References
Fig. 6
Patient’s mother with a pseudocleft of the lip.
[1] W.K. Lee, A.W. Root, N. Fenske, Bilateral branchial cleft sinuses associated with intrauterine and postnatal growth retardation, premature aging and unusual facial appearances: a new syndrome with dominant transmission, Am. J. Med. Genet. 11 (1982) 345—352. [2] B.D. Hall, A. de Lorimer, L.H. Foster, A new syndrome of hemangiomatous branchial clefts, lip pseudoclefts, and unusual facial appearance, Am. J. Med. Genet. 14 (1983) 135— 138. [3] A. Fujimato, M. Lipson, R.V. Lacro, N.W. Shinno, W.D. Boelter, R.L. Jones, New automosal dominant branchio-oculo-facial syndrome, Am. J. Med. Genet. 27 (1987) 943—951. [4] S. Schmerler, T. Kushnick, F. Desposito, Long term evaluation of a child with the branchio-oculo-facial syndrome, Am. J. Med. Genet. 44 (1992) 177—178. [5] A.E. Lin, H.W. Losken, R. Jaffe, A.W. Biglan, The branchiooculo-facial syndrome, Cleft Palate Craniofac. J. 28 (1991) 96—102. [6] A.E. Lin, R.J. Gorlin, I.W. Lurie, H.G. Brunner, I. Van der Burgt, I.V. Naumchik, Further delination of the branchiooculo-facial syndrome, Am. J. Med. Genet. 56 (1995) 42—59. [7] A.E. Lin, E.V. Semina, S.D. Hirsch, E.R. Roeder, C.J.R. Curry, K. Rosenbaum, Exclusion of the branchio-oto-renal syndrome locus (EYA1) from patients with branchio-oculo-facial syndrome, Am. J. Med. Genet. 91 (2000) 387—390. [8] E. Legius, J.P. Fryns, Branchio-oculo-facial and branchio-otorenal syndromes are distinct entities, Clin. Genet. 41 (1992) 223. [9] E. Legius, J.P. Fryns, I. Van der Burgt, Dominant branchial cleft syndrome with characteristics of both branchio-otorenal and branchio-oculo-facial syndrome, Clin. Genet. 37 (1990) 347—350.