Clinical and imaging correlations of Treacher Collins syndrome:

Report of two cases

Marina H. C. G. Magalhães, DDS, PhD,a Cristiane Barbosa da Silveira,b
Carla Ruffeil Moreira, DDS, MSc,c and Marcelo Gusmão Paraíso Cavalcanti, DDS, PhD,d
São Paulo, SP, Brazil
UNIVERSITY OF SÃO PAULO

Mandibulofacial dysostosis (Treacher Collins Syndrome) is an autosomal dominant genetic disorder that
probably derives from inhibition of the facial structures from the first and second branchial arches. The facial pattern
of the syndrome is a convex facial profile with a prominent nose above a retruded chin. The eyes are deformed by
antimongoloid slant of the palpebral fissures and facial bones are hypoplastic. The alterations are caused by mutation
in gene 5q32-33.1, which encodes the nucleolar phosphoprotein treacle. Computed tomography images are able to
demonstrate craniofacial bones, allowing the morphological analysis of these bones in individuals with complex
deformities. The purpose of this paper is to present the results of a clinical and computed tomography investigation of
two patients with Treacher Collins syndrome. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:836-42)

Mandibulofacial dysostosis (MFD), or Treacher Collins
syndrome, is an autosomal dominantly inherited disor-
der that arises from aberrations in the development of
the facial structures derived from the first and second
branchial arches during histodifferentiation morpho-
genesis between approximately the 20th day and the
12th week of intrauterine life.1
Although MFD was first reported in 1846 by Thomp-
son,2 it is known by the eponym of a British ophthal-
mologist named Treacher Collins, who reported 2 cases
of the syndrome in 1900.3 Later, in 1944, Franceschetti
and Klein4 wrote an extensive revision of the described
cases and proposed the term “mandibulofacial dysos-
tosis,” which is recognized in the literature. The inci-
dence is estimated at 1 in 50000 live births,5 and in
approximately 40% of cases, the transmission is of
autosomal dominant character with penetrance close to
100%, and variable expressivity.
In cases of full expression of the syndrome, the
diagnosis is easily made based on clinical characteris-
tics alone. These occur as a result of the destruction of
This research was funded by CAPES, Brasilia, Brazil (C. R. M.) for
PhD scholarship.
a
Associate Professor, Oral Pathology, Dentistry School, University of
São Paulo.
b
Undergraduate Student, Dentistry School, University of São Paulo.
c
PhD Student, Bauru School of Dentistry, University of São Paulo.
d
Associate Professor, Oral Radiology, Dentistry School, University
of São Paulo.
Received for publication Dec 16, 2005; returned for revision Mar 9,
2006; accepted for publication Apr 22, 2006.
1079-2104/$ - see front matter
© 2007 Mosby, Inc. All rights reserved.
doi:10.1016/j.tripleo.2006.04.011
the neural crest cells before they migrate to form the
facial processes.6 Normally derived structures of the
first and second branchial arches exhibit malformation.
Mandibulofacial dysostosis can be recognized at birth
given the characteristic facial appearance, or may be
noticed after the first months of life. The wide variation
in the phenotypic expression of different patients, to-
gether with the fact that more than 60% of cases arise
from new mutations, can complicate the diagnosis of
mild cases and raise challenges for genetic counsel-
ors.7,8 This suggests that modifying factors are impor-
tant for phenotypic expression. Based on these findings,
Teber et al.9 defined minimal diagnostic criteria such as
downward slanting palpebral fissures and hypoplasia of
the zygomatic arch. The most common clinical mani-
festations of MFD are summarized on Table I.
In syndromic and nonsyndromic craniofacial anom-
alies, computed tomography (CT) has been used to
determine and document abnormal anatomic structures.
This allows both diagnosis and development of the
correct treatment plan. Further, it permits assessment of
the results obtained after surgical intervention of these
complex disorders.10-14 Santos et al.10 pointed out the
value of CT in diagnosis and treatment planning in
patients with Goldenhar syndrome by using three-di-
mensional reconstructed images from CT.
The aim of this study is to describe 2 cases of MFD
with full expression and to discuss the clinical charac-
teristics and the computed tomography findings.
CASE REPORTS
Case 1
A 7-year-old white female came to the Special Care Den-
tistry Center at the School of Dentistry in 1996 for dental

836
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Volume 103, Number 6
Table I. Most frequent clinical characteristics of man-
dibulofacial dysostosis
● Antimongoloid slant of the palpebral fissure
● Malar hypoplasia
● Mandibular hypoplasia
● Coloboma
● Total or partial absence of lower eyelashes
● External ear malformations
● Conductive hearing loss
● Cleft palate
● Shortened soft palate
● Tongue-shaped process of hair in the face
● Macrostomia
● Malocclusion
● Enamel hypoplasia
● Open bite
● Congenital cardiac malformations (Tetralogia de Fallot)
● Cervical vertebrae malformation
● Kidney malformations
● Extremity malformations
● Oligofrenia (5% of cases)
● Obstructive apnea (25% of cases)
● Curved inferior mandible border
treatment. During the medical history, an ear surgical proce-
dure to correct facial aesthetics, closing of cleft palate, and a
hard palate expansion when the patient was 2 years old was
noted. In addition, when she was 5 years old, the correction of
eyelid coloboma was carried out followed by orbital recon-
struction with calvarial bone grafts. She had age-appropriate
mental development.
The extraoral examination revealed a narrow face with an
external ear abnormality, absence of opening from the exter-
nal to the internal ear, conduction deafness with 50% reduc-
tion in hearing, microtia, inferior palpebral coloboma, anti-
mongoloid slant of both palpebral fissures, and a prominent
nose. This condition had not progressed over time. On the
intraoral exam, an accentuated anterior open bite, trismus, and
narrowing of the soft palate were noted. Oral hygiene was
poor and was associated with dental caries and gingivitis
(Fig. 1).
In the succeeding 9 years, the patient had no further orth-
odontic therapy or surgical procedure. The mouth opening
improved, but the maxillomandibular discrepancy had in-
creased (Fig. 2). Considering the limitation of mouth opening,
the patient was generally in good health. Speech and language
development was delayed and abnormal probably due to
bilateral partial hearing loss.
Subsequently, the patient was imaged using coronal and
axial CT, which showed mandibular micrognathia, bilat-
eral mandibular condylar hypoplasia, and bone resorption
on the internal portion of the left condyle (Fig. 3, A). Other
findings included absence of the coronoid processes, hyp-
oplasia of the maxilla and malar bones, narrowing of the
frontal bone, hypertrophy of both maxillary sinus walls,
atresia of both auricular conducts, (Fig. 3, B) and fusion of
C1 with C2 (Fig. 3, C).
Examination of the soft tissue revealed diminished devel-
Magalhães et al. 837
opment of the temporal and masseter muscles (Fig. 3, D) on
the left side, with a decrease in oropharyngeal space. Using
information from the clinical examination and radiographic
imaging, a comprehensive treatment plan was developed.
This included presurgical orthodontic preparation of the den-
tition for maxillary expansion and distraction surgery of the
maxilla, as well as bilateral sagittal split osteotomy for ad-
vancement and rotation of the mandible.
Case 2
A 13-year-old black male patient came to the Special Care
Dentistry Center at the School of Dentistry for routine dental
treatment. The diagnosis of MFD was established based on
clinical criteria by geneticists. Physical examination of the
patient showed antimongoloid slants of the palpebral fissures,
mandibular and zygomatic hypoplasia, coloboma of the lower
eyelid, absence of lower eyelashes, abnormal external ears,
50% bilateral conductive hearing loss, and hair on the lateral
side of the face (Fig. 4). The oral examination revealed an
anterior open bite and dental caries on the upper right and left
first molars.
The patient was then submitted to axial and coronal CT
examinations. Mandibular hypoplasia of the condylar region
and coronoid processes (Fig. 5, A) were noted, as were
maxillary hypoplasia (Fig. 5, B); bilateral zygomatic hypopla-
sia (Fig. 5, C); atresia of both auricular canals; narrowing of
the frontal bone; hypertrophy of the nasal conchae (Fig. 5, D);
bilateral diminished development of the temporal, masseter,
and pterygoid muscles; and a decreased oropharyngeal space.
The patient has been followed for 1 year. During this time,
orthodontic expansion of the maxilla in preparation for or-
thognathic surgical procedure has been progressing satisfac-
torily.
The clinical and radiographic findings of both patients are
summarized in Tables II and III.
Depending on the severity of the abnormality of the middle
ear, found on CT, the treatment of this condition may involve
reconstructive surgical procedure of the outer ear and/or the
middle ear, or the provision of suitable hearing aids. In the
present cases, CT was not essential in establishing the diag-
nosis, but was important in surgical planning. After the or-
thognathic surgical procedure, CT reexamination allows ob-
jective documentation of the results of the surgical procedure.
DISCUSSION
The adult with fully expressed MFD has a convex
facial profile with a prominent nose and a retruding
chin. The eyes are deformed by antimongoloid slants of
the palpebral fissures, hypoplastic lower eyelids, partial
absence of eyelash, and inferolateral dystopia. There
are colobomas of the lower lids and lateral canthi.
Tongues of hair extend onto the cheeks, which them-
selves are deformed by underlying osseous clefts. The
external ears are absent or malpositioned and hearing is
impaired.6 All of the aforementioned describe clinical
characteristics present in both our patients (Table II).
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838 Magalhães et al. June 2007

Fig. 1. Clinical aspect of patient 1 when she was 7 years old. Narrowed face with an external ear abnormality, A and B.
Accentuated anterior open bite and limitation of the mouth opening, C and D.

Fig. 2. Current clinical appearance. A and B, Increased maxillomandibular discrepancy. C and D, Increased mouth opening.

The clinical aspects associated with CT findings of breathing. The retruding chin and associated abnormal
mandibular and maxillary hypoplasia are presented in curvature of the mandibular body results in posterior
Tables II and III. Hypoplasia of the maxilla is accom- and anterior open bite. This hinders normal mastication
panied by a high palatal vault and predisposes to mouth and mouth opening.
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Volume 103, Number 6 Magalhães et al. 839

Fig. 3. A, CT coronal slice showing hypoplasia and bone resorption on the internal portion of the left condyle. B, CT axial slice
demonstrating atresia of both auricular conducts and hyperdensity of the right temporal bone. C, CT coronal slice depicting
junction of C1 and C2. D, CT axial slice showing a left masseter muscle hypotrophy.

Fig. 4. A and B, Clinical appearance of patient 2, demonstrating antimongoloid slants of the palpebral fissures, mandibular and
zygomatic hypoplasia, coloboma of the lower lid, and absence of lower eyelid cilia. C and D, Anterior open bite and narrowed palate.

The structural abnormalities observed in MFD may complex, and a differential diagnosis is needed to es-
compromise the airway and also diminish hearing. This tablish the correct treatment and evaluate clinical out-
has an effect on resonance, voice quality, and articula- comes.15
tion. The speech abnormalities of these patients are The syndrome should be differentiated from other
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840 Magalhães et al. June 2007

Fig. 5. A, CT coronal slice showing a bilateral condylar hypoplasia. B, CT axial slice depicting maxillary hypoplasia. C, CT
coronal slice showing a bilateral zygomatic hypoplasia. D, CT coronal view demonstrating narrowed frontal bone and conchae
hypertrophy.

Table II. Clinical aspects observed in both cases Table III. Radiographic aspects showed in computed
Clinical findings Case 1 Case 2 tomography in both cases
Antimongoloid slant of the palpebral fissure ⫹ ⫹ Radiographic characteristics Case 1 Case 2
Coloboma ⫹ ⫹ Mandibular hypoplasia ⫹ ⫹
Absence of eyelashes ⫹ ⫹ Bilateral condilar hypoplasia ⫹ ⫹
Malar hypoplasia ⫹ ⫹ Coronoid process absence/hypoplasia ⫹ ⫹
Retrusive mandible ⫹ ⫹ Maxilar bone hypoplasia ⫹ ⫹
Lower implantation of the external ear ⫹ ⫹ Malar bone hypoplasia ⫹ ⫹
External ear deformity ⫹ ⫹ Narrowed frontal bone ⫹ ⫹
Absence of communication between internal ⫹ ⫺ Maxillary sinus walls hypertrophy ⫹ ⫺
and external acoustic meatus Auricular canals atresia ⫹ ⫹
Narrowed palate ⫹ ⫹ C1–C2 fusion ⫹ ⫺
Cleft palate ⫹ ⫹ Temporal muscle hypotrophy ⫹ ⫹
Open bite ⫹ ⫹ Masseter muscle hypotrophy ⫹ ⫹
Shortened soft palate ⫹ ⫺ Lateral pterygoid hypotrophy ⫺ ⫹
Blind fistula ⫺ ⫺ Decreased oropharyngeal space ⫹ ⫹
Facial implantation of hair ⫺ ⫹ Conchae hypertrophy ⫺ ⫹
Narrowed frontal bone ⫹ ⫹
⫹, presence; ⫺, absence.
⫹, presence; ⫺, absence.

diseases such as Nager acrofacial dysostosis, which
presents involvement of superior extremities in ad-
dition to facial abnormalities, and Goldenhar syn-
drome, which is characterized by hemifacial micro-
somia and vertebral abnormalities somewhat similar
to MFD.1
Santos et al.10 published clinical-embryological and
radiological correlations of Goldenhar syndrome by
using three-dimensional CT. They noted atresia of the
pinna, unilateral clefting, ocular disturbances, and bi-
lateral ear and skin tags in patients with Goldenhar
syndrome. The CT findings in MFD are shown in Table
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Volume 103, Number 6
III. Analysis of the CT findings, in combination with
the clinical characteristics, permits the differentiation
of MFD from other craniofacial anomalies.
Early diagnosis of MFD allows prompt and appro-
priate treatment of aesthetic and functional deficiencies
in these patients. If this can be done early, it is possible
to take advantage of anticipated growth during normal
skeletal maturation and to obtain better therapeutic
results. Ameliorating the outward signs of MFD gives
these patients the opportunity to have an improved
social life. An experienced multidisciplinary team of
orthodontists and maxillofacial surgeons is necessary
for good results since the method of choice in the
treatment of MFD is distraction osteogenesis associated
with preoperative and postoperative orthodontic treat-
ment.16
Through the increased diagnostic quality of its im-
ages, CT has become the examination of choice for
confirming the working diagnoses of craniofacial syn-
dromes. The value of CT in the quantitative and qual-
itative analysis of this condition is pivotal, since it
provides a wealth of information, and the high quality
of the images allows clear recognition of the alterations
in the craniofacial complex. Using CT, greater detail
and clinical conception of syndrome-related alterations
present in patients with craniofacial anomalies is per-
mitted.10-14
In MFD patients, CT images demonstrate atresia of
both internal auditory canals and hypoplasia of the
zygomatic bone.13 Computed tomography has taken a
leading role in both diagnosis and surgical correction of
craniofacial dysmorphology, including MFD.13-14
Cranio-orbito-zygomatic measurements obtained from
CT agree with the clinically observed morphology of
MFD.14
Computed tomography imaging is useful in both
diagnosis and planning of surgical intervention. Axial
and coronal images should be obtained to accurately
delineate the bony labyrinth, middle ear, and facial
nerves. The scan can help identify contraindications to
surgical procedure, such as gross anomalies of the inner
ear. In addition, quantitative volumetric analysis of CT
scans is an accurate method to measure the amount of
bone generated in patients during distraction osteogen-
esis of the mandible or maxilla.17
According to Posnick et al.,14 CT showed neither
hypotelorism nor hypertelorism of the orbits with
MFD. The measurements carried out in the upper mid-
face structures confirmed the degree of hypoplasia of
the zygomas. Posnick et al.14 observed that patients
with MFD have a narrow upper face, narrow forehead
and temporal region, and a decreased intercoronal dis-
tance, even though the reason for the latter was unclear.
Magalhães et al. 841
Both related cases presented the CT findings of hypo-
plastic and narrowed bones (Table III).
Jahrsdoerfer et al.18 described 3 radiographic find-
ings that are characteristic of a MFD patient: (1) ab-
sence of mastoid pneumatization, (2) ossicular disjunc-
tion, and (3) a bony cleft in the lateral aspect of the
temporal bone just anterior to the mastoid. These were
visualized on three-dimensional images. The patients
presented did not show these characteristic CT findings
(Table III), although they presented many other char-
acteristics of MFD (Tables I-III).
Other studies reported hypoplastic zygomatic
arches, hypoplastic mandible with retrognathism, ab-
sent external auditory canal, atresia, or abnormalities
of the ears.13,18,19 These were present in our 2 pa-
tients (Table III).
Pron et al.20 described CT imaging of the temporal
bone, with special attention for the external auditory
canal and the ossicular chain in relation to audiologic
abnormalities in MFD patients. One of the present
patients exhibited a relationship between CT findings
and deafness. According to Kaga et al.,13 CT confirmed
the clinical diagnosis and provided morphological to-
pography of abnormal skull and facies in MFD patients.
In conclusion, there is a correlation between the
clinical and radiological findings in MFD patients.
Computed tomography was extremely useful in the
diagnosis and recognition of facial characteristics and
allowed appropriate treatment planning and postsurgi-
cal reevaluation. Computed tomography images can be
used as an anatomical and a morphological “map” to
help in the diagnosis, treatment planning, and the post-
surgical management of patients with MFD syndrome.
We thank Dr. Margareth Romao for grammatical
assistance. The Section Editor acknowledges with thanks
the outstanding efforts put forward by Dr. Robert Wood
(Toronto, Canada) in scientifically editing the submitted
manuscript.
REFERENCES
1. Gorlin RJ, Cohen MMJr, Levin LS. Syndromes of the head and
neck. 3rd ed. New York: Oxford; 1990. p. 649-51.
2. Thomson A. Notice of several cases of malformation of the
external ear, together with experiments on the state of hearing in
such persons. Mont J Med Sci 1846-1847;7:420.
3. Collins ET. Cases with symmetrical congenital notches in the
outer part of each lower lid and defective development of the
malar bones. Trans Ophthal Soc UK 1933;20:190-2.
4. Franceschetti A, Klein D. Mandibulo-facial dysostosis: new he-
reditary syndrome. Acta Ophthal 1949;27:143-224.
5. National Organization for Rare Disorders Rare Disease Database
[serial on the Internet]. 1999 [cited 2003 Sept 11]. Available
from: http://www.rarediseases.org.
6. Van Vierzen PB, Joosten FBM, Marres HAM, Cremers CWRJ,
Ruijs JHJ. Mandibulofacial dysostosis: CT findings of the tem-
poral bones. Eur J Radiol 1995;21:53-7.
 OOOOE
842 Magalhães et al. June 2007

7. Dixon J, Ellis I, Bottani A, Temple K, Dixon MJ. Identification
of mutations in TCOF1: use of molecular analysis in the pre- and
postnatal diagnosis of Treacher Collins syndrome. Am J Med
Genet A 2004;127:244-8.
8. Marszalek B, Wojcicki P, Kobus K, Trzeciak WH. Clinical
features, treatment and genetic background of Treacher Collins
syndrome. J Appl Genet 2002;43:223-33.
9. Teber OA, Gillessen-Kaesbach G, Fischer S, Bohringer S, Al-
brecht B, Albert A, et al. Genotyping in 46 patients with tentative
diagnosis of Treacher Collins syndrome revealed unexpected
phenotypic variation. Eur J Hum Genet 2004;12:879-90.
10. Santos DT, Miyazaki O, Cavalcanti MG. Clinical-embryological
and radiological correlations of oculo-auriculo-vertebral spec-
trum using 3D-CT. Dentomaxillofac Radiol 2003;32:8-14.
11. Vannier MW, Pilgram TK, Marsh JL, Kraemer BB, Rayne SC,
Gado MH, et al. Craniosynostosis: diagnostic imaging with
three-dimensional CT presentation. AJNR Am J Neuroradiol
1994;15:1861-9.
12. Albuquerque MAP, Cavalcanti MGP. Computed tomography
assessment of Apert syndrome. Braz Oral Res 2004;18:35-9.
13. Kaga K, Yamasoba T, Nakamura M, Kaneko M, Ino K. Aplasia
of zygomatic arch and dislocation of temporomandibular joint
capsule in Treacher-Collins syndrome: three-dimensional recon-
struction of computed tomography scans. Int J Pediatr Otorhino-
laryngol 2003;67:1189-94.
14. Posnick JC, al-Qattan MM, Moffat SM, Armstrong D. Cranio-
orbito-zygomatic measurements from standard CT scans in un-
operated Treacher-Collins syndrome patients: comparison with
normal control. Cleft Palate Craniofac J 1995;32:20-24.
15. Vallino-Napoli LD. A profile of the features and speech in
patients with mandibulofacial dysostosis. Cleft Palate Craniofac
J 2002;39:623-34.
16. Opitz C, Ring P, Stoll C. Orthodontic and surgical treatment of
patients with congenital unilateral and bilateral mandibulofacial
dysostosis. J Orofac Orthop 2004;65:150-63.
17. Lowe LH, Booth TN, Joglar JM, Rollins NK. Midface anomalies
in children. Radiographics 2000;20:907-22.
18. Jahrsdoerfer RA, Yeakly JW, Aguilar EA, Cole RR. Treacher
Collins syndrome: an otologic challenge. Ann Otol Rhinol Lar-
yngol 1989;98:807-12.
19. Binaghi S, Gudinchet F, Rilliet B. Three-dimensional spiral CT
of craniofacial malformations in children. Pediatr Radiol
2000;30:856-60.
20. Pron G, Galloway C, Armstrong D, Posnick J. Ear malformation
and hearing loss in patients with Treacher Collins syndrome.
Cleft Palate Craniofac J 1993;30:97-103.
Reprint requests:
Marina H. C. G. Magalhães
Rua Filadelfo Aranha, 95
05449-100
São Paulo, SP, Brazil
mhcgmaga@usp.br