Townes-Brocks syndrome with overlapping features of hemifacial microsomia

Yadavalli Guruprasad; Dinesh Singh Chauhan

doi:10.4103/0975-8844.113693

CASE REPORT

Year : 2013 | Volume : 5 | Issue : 1 | Page : 42-46

Townes-Brocks syndrome with overlapping features of hemifacial microsomia

Yadavalli Guruprasad, Dinesh Singh Chauhan
Department of Oral and Maxillofacial Surgery, AME'S Dental College Hospital and Research Centre, Raichur, Karnataka, India

Date of Web Publication

20-Jun-2013

Correspondence Address:
Yadavalli Guruprasad
Department of Oral and Maxillofacial Surgery, AME'S Dental College Hospital and Research Centre,Raichur - 584 103, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0975-8844.113693

Abstract

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder with multiple malformations and variable expression. Major findings include external ear anomalies, hearing loss, limb deformity, imperforate anus, and renal malformations. Intelligence is usually normal, although mild moderate mental retardation has been reported. It can be difficult to differentiate clinically between hemifacial microsomia (HFM) and Townes-Brocks syndrome (TBS). The distinction is important because TBS is inherited as an autosomal dominant trait, whereas HFM is sporadic. We report a classical case of TBS with overlapping features of hemifacial microsomia in an 11 year old boy who presented with unilateral anotia with hearing defect, renal agenesis and imperforate anus by birth.

Keywords: Anotia, chromosome 16q12.1, hemifacial microsomia, imperforate anus, renal agenesis, Townes-Brocks syndrome

How to cite this article:
Guruprasad Y, Chauhan DS. Townes-Brocks syndrome with overlapping features of hemifacial microsomia. J Orofac Sci 2013;5:42-6

How to cite this URL:
Guruprasad Y, Chauhan DS. Townes-Brocks syndrome with overlapping features of hemifacial microsomia. J Orofac Sci [serial online] 2013 [cited 2023 Jun 9];5:42-6. Available from: https://www.jofs.in/text.asp?2013/5/1/42/113693

Introduction

Hemifacial microsomia (HFM) and Townes-Brocks syndrome (TBS) have overlapping phenotypic features, and it can be difficult to differentiate between these two disorders. The classic triad of TBS includes anal anomalies (such as imperforate anus), hand and thumb anomalies, and auricular anomalies. Craniofacial abnormalities, including mandibular asymmetry, are rare in TBS. HFM with expanded spectrum (sometimes referred to as oculo-auricular-vertebral spectrum or "Goldenhar syndrome") includes mandibular hypoplasia, cranial nerve weakness, auricular, vertebral, and ocular anomalies, most commonly epibulbar dermoids.

It is essential to accurately diagnose TBS because it is inherited in an autosomal dominant fashion and, thus, has a 50% rate of transmission to offspring. HFM, on the other hand, is thought to be sporadic, and a 2-3% recurrence rate is generally quoted to families with an affected child.

Townes-Brocks syndrome (TBS) is an autosomal dominant multiple malformation syndrome characterized by external ear malformations with sensorineural hearing loss, thumb anomalies, and anorectal malformation. Intelligence is usually normal, although mild-moderate mental retardation has been reported. Townes and Brocks first described the syndrome in 1972. The gene for Townes-Brocks syndrome was mapped to 16q12. ^[1] through identifying subjects with TBS and cytogenetic abnormalities. ^{[1],[2],[3],[4]} Mutations in a candidate gene, SALL1, have been found in one family and in an isolated case with typical features of this syndrome. Diagnostic criteria suggested for TBS include two or more of the following: (1) anorectal malformation (imperforate anus, anteriorly placed anus, anal stenosis); (2) hand malformation (preaxial polydactyly, triphalangeal thumb, bifid thumb); (3) external ear malformation (microtia, "satyr" or "lop" ear, preauricular tags or pits) with sensorineural hearing loss; (4) a relative with the syndrome. REAR syndrome (renal-ear-anal-radial) has also been a term used to describe this condition. ^[5] We report a classical case of TBS in an 11 year old boy who presented with unilateral anotia with hearing defect, renal agenesis and imperforate anus by birth with overlapping features of hemifacial microsomia.

Case Report

An 11 year old male patient was referred to department of oral and maxillofacial surgery with a chief complaint of asymmetry of the face with congenital absence of right ear [Figure 1] and [Figure 2]. The patient was born of non-consanguineous marriage to a mother with no antenatal complications. On further evaluation through history from parents revealed that the child was born with absence of right kidney along with absence of anal opening which was surgically treated immediately after birth. Orthopantomogram (OPG) showed hypoplastic mandible on the left side with absence of well formed condyle and coronoid process along with absence of external auditory canal [Figure 3]. Further examination led to presence of mild right thumb and index finger syndactyly. The patient was suspected for syndromic disorder and all the past investigative records were evaluated. Cross-table lateral radiograph with the baby in prone position taken on second day after birth showed a radio-opaque marker placed on the anal dimple, showing an air-fluid level with a short distance between the air-filled rectum and the marker suggestive of imperforate anus [Figure 4]. Cross-table lateral radiograph with the baby in prone position taken with barium enema confirmed the diagnosis of imperforate anus [Figure 5]. Contrast enhanced CT scan showed absence of right kidney [Figure 6]. Differential diagnosis included hemifacial microsomia, Goldenhar syndrome (Oculoauriculovertebral syndrome) and Branchiootorenal (BOR) syndrome because some clinical features were overlapping with the present case. With all the clinical features and reviewing the past and present investigative records a diagnosis of Townes-Brocks syndrome was made.

Figure 1: Extraoral view showing anotia on the right side causing asymmetry of the face

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Figure 2: Right lateral view showing anotia with a skin tag

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Figure 3: Orthopantomogram showing hypoplastic mandible on the right side with absence of well formed condyle and coronoid process. Note the absence of external auditory canal

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Figure 4: Cross-table lateral radiograph with the baby in prone position taken on second day after birth shows a radio-opaque marker placed on the anal dimple. Image shows an air-fluid level with a short distance between the air-filled rectum and the marker suggestive of imperforate anus

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Figure 5: Cross-table lateral radiograph with the baby in prone position taken with barium enema confirming imperforate anus

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Figure 6: Contrast enhanced CT scan view showing absence of right kidney

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Discussion

The Townes-Brocks syndrome derives its eponymous title from the names of the two authors who, in 1972, described variable anal, hand, foot, and ear anomalies in a father and five of his seven children. Shortly afterwards, similar abnormalities were documented in 19 subjects from four generations of a large Australian family. Subsequent reports of both familial and isolated cases have established the Townes-Brocks syndrome as a discrete entity and enabled fuller delineation of the phenotype of what appears to be a relatively rare disorder. ^[1],[5]

TBS is estimated to occur in 1:250,000 live born but may be misdiagnosed because its defects overlap with those of other genetic diseases. TBS is inherited in an autosomal dominant manner. Penetrance seems complete, but expressivity is highly variable. SALL1 is the only gene known to be associated with TBS; about half of cases are caused by de novo mutations. SALL1 encodes sal-like protein 1, a C2H2 zinc finger transcription factor of the SAL type. Sal-like protein 1 appears to be an essential developmental regulator, which interacts with SALL4 and is regulated by TBX5. The majority of reported mutations in SALL1 are nonsense and frameshift mutations that positioned in exon 2 of the gene and resulted in premature stop codons. Both haploinsufficiency and dominant-negative effects of mutated SALL1 protein have been proposed for the pathogenesis of TBS. ^[5],[6]

TBS is characterized by anal, auricular, renal and hand anomalies. Anal abnormalities have been reported to occur in 95-97% of patients with TBS. The most common anal anomaly reported is imperforate anus, varying in degree from a skin covered opening to more severe grades of imperforation. ^[7] There is often a rectovaginal or rectourethral fistula. Anal stenosis without imperforate anus has also been reported. ^[8] Excess perianal skin was also noted in several members of a large kindred with probable TBS reported by Reid and Turner. ^[9] Unilateral and bilateral auricular anomalies include "lop" or "satyr" ear, microtia, auricular pits, and tags, and sensorineural and/or conductive hearing loss. ^[10] Hearing loss is common in TBS, ranging from mild to profound. ^[11],[12] It is usually congenital and primarily sensorineural, although a small conductive component is often present. ^[13] At least in some patients it is progressive, and is worse in the high frequencies. ^[14],[15] Structural middle ear anomalies have been reported and include hypoplastic malleus head and abnormally shaped oval window and incus. ^[16] Renal anomalies are often seen, but less consistently so, and include hypoplastic or dysplastic kidneys, renal agenesis, multicystic kidneys, posterior urethral valves, and vesicoureteral reflux. Other associated anomalies of the genitourinary system are bifid scrotum and hypospadias. ^[17]

The most common limb malformations are triphalangeal thumb and preaxial polydactyly with a well formed or vestigial digit. Bifurcation, ulnar deviation, or broad appearance of the distal phalanx of the thumb are also common. Finger syndactyly has been reported in some patients with TBS. ^[17] Toe anomalies occur less frequently than thumb anomalies but those described include short third toe/metatarsal, overlapping toes (typically second and fourth overlapping third), syndactyly of the third and fourth toes, and absent third toe. Hypoplasia of the thumb and radial bone abnormalities are not features of TBS and should raise the likelihood of an alternative diagnosis in isolated or familial cases. Reports of TBS in patients with hypoplastic thumbs and radial anomalies probably do not represent true TBS. ^[17],[18] Vertebral defects have been described in only one TBS patient, and it has been proposed that this feature be used to differentiate TBS from VACTERL association or other overlapping conditions with vertebral anomalies. The VACTERL association comprises v ertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal malformations, and limb defects. VACTERL is therefore an important differential diagnosis for simplex cases (i.e., a single affected individual in a family) with suspected TBS. To date, severe vertebral defects and tracheo-esophageal fistula have not been observed in persons with SALL1 mutations. ^[18],[19]

Mental retardation is not typically associated with TBS. Walpole and Hockey described a 29 year old female patient with typical features of the syndrome with severe behavioural problems and mild intellectual handicap. This was attributed to late diagnosis (aged 6) of her hearing loss. ^[19] Cameron et al., described two children with Townes-Brocks syndrome with mental retardation. One was a 9 year 8 month old female with ear anomalies, anteriorly placed anus, and supernumerary thumb. She had mild mental retardation (full scale IQ of 60). The second was an unrelated 14 year old male with a positive family history of TBS. He had an imperforate anus, small ears with preauricular tags, and normal thumbs. He had moderate mental retardation (full scale IQ of 47). Although his mother and sister also had features of TBS with thumb anomalies, both had normal intelligence. ^[20]

Our patient had the following features right anotia with loss of hearing, absence of right kidney, imperforate anus and right finger syndactyly which was conclusive of TBS. TBS coincides with a series of syndromes such as hemifacial microsomia, Goldenhar syndrome (Oculoauriculovertebral syndrome) and Branchiootorenal (BOR) syndrome.

Clinical differentiation between TBS and HFM-expanded spectrum can be confusing. TBS is characterized by the triad of anal, auricular, and hand anomalies. Anal abnormalities have been reported to occur in 95-97% of patients with TBS. Unilateral and bilateral auricular anomalies include "lop" or "satyr" ear, microtia, auricular pits, and tags, and sensorineural and/or conductive hearing loss. Renal anomalies are often seen, but less consistently so, and include hypoplastic or dysplastic kidneys, renal agenesis, multicystic kidneys, posterior urethral valves, and vesicoureteral reflux. ^[21] Other associated anomalies of the genitourinary system are bifid scrotum and hypospadias. Vertebral defects have been described in only one TBS patient, and it has been proposed that this feature be used to differentiate TBS from VATER association or other overlapping conditions with vertebral anomalies. The occurrence of intrafamilial phenotypic variability in TBS has been well described. ^[21]

HFM is characterized by asymmetrical hypoplasia of the facial skeleton, ear, and facial soft tissues. Extracraniofacial anomalies occur in approximately 50% of patients. There is significant variability in this condition, with the exception of facial asymmetry. Although there are no universally used diagnostic criteria, most studies include mandibular and auricular defects as obligatory features. ^[22]

Acknowledgment

The author would like to thank the patient for providing consent to use his photograph in this article.

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