Case report of Treacher–Collins syndrome with a review of its pathogenesis

INTRODUCTION

Treacher–Collins syndrome (TCS) is a rare orofacial anomaly which is also known as Franceschetti–Zwahlen–Klein syndrome and mandibulofacial dysostosis. In the year 1846, Thomson presented this disorder for the 1^st time,and later in 1889, George Andreas Berry designated it as a congenital deformity with the presence of coloboma of the lower eyelids. Edward Treacher Collins, a renowned British ophthalmologist, first illustrated this orofacial anomaly in 1900. Pathogenesis of TCS is related to the aberrations occurred in the embryonal craniofacial structures derived from the first and second branchial arches during their histodifferentiation and morphogenesis stage between the 20^th day and 12^th week of intrauterine life.^[1] Literature review shows that the estimated incidence of TCS is about 1 among 50000 live births.^[2] Nearly 60% cases of TCS appear as de novo mutations.

Clinically, the affected individuals exhibit underdevelopment of cheekbones, jaws, and palate, along with downward slanting of palpebral fissures. Anomalies of the external and middle ear often leading to partial or complete hearing loss are also seen.^[3] Microcephaly, behavioral disorders, and psychomotor delay are also reported in TCS.^[4]

Dental anomalies, namely malocclusion, misaligned teeth, enamel hypoplasia, spacing, hypodontia, and anterior open bite, are seen in TCS. High arched palate with or without palatal cleft is also reported in many cases of TCS.

Patients with TCS may exhibit mental retardation or normal intelligence level. However, the appearance of the patients may lead to social challenges and social stigma.

CASE REPORT

A 21-year-old female patient reported to the Department of Oral and Maxillofacial Pathology of a tertiary health care center with a complaint of pain in the right lower back tooth region. After recording proper history, extraoral clinical examination was performed, which revealed a narrow, convex facial profile with mandibular and zygomatic hypoplasia [Figure 1a] along with antimongoloid slanting of both eyes [Figure 1b]. Eyelashes in the lower eyelid were partially absent. The maxilla was constricted with protrusion of the upper anterior teeth. There was “sunk-in” appearance of the face, causing the nose to be very prominent. Bilateral microtia with rudimentary pinna was also noted [Figure 1c]. In addition, atresic external ear canals and absence of external ear opening were also noted. The patient had deafness with a 60% reduction in hearing. Intraoral examination showed “V” shaped, narrow, high-arched palate [Figure 1d], crowded alignment of teeth in both arches, multiple carious teeth (11, 36, 37, 46), retained root of deciduous tooth (52), and macroglossia [Figure 1a]. The patient had an open bite and a history of cleft palate. The cleft palate was repaired at the age of 2 years in the patient. Prominent antegonial notch and “double-chin” appearance were also found. The patient had a sibling but he had no such abnormalities. At the time of her birth, the paternal and maternal ages were 30 years and 27 years, respectively. There was no familial history of this disorder. No psychomotor delay or behavioral abnormalities were reported.

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Figure 1:

A 21-year-old female patient presented with features of Treacher–Collins syndrome. (a) Frontal profile of the patient showing dental malocclusion, (b) antimongoloid slanting of both eyes with partial absence of eyelashes in the lower eyelid, (c) ear deformity, (d) high-arched palate, (e) lateral cephalogram of the patient showing mandibular hypoplasia, prominent antegonial notches, open bite, and convex facial profile.

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Lateral cephalogram of the patient was done and it revealed mandibular hypoplasia, prominent antegonial notches, open bite, and convex facial profile [Figure 1e].

Based on the clinical and radiological findings, a diagnosis of TCS was made.

DISCUSSION

TCS or mandibulofacial dysostosis is one of the autosomal dominant disorders with incomplete penetrance and variable expressivities.^[5] Pathogenesis of TCS may be attributed to the responsible gene TCOF1 which is located on chromosome no 5 at q31 and 3q32. This gene was identified in 1996. 51 mutations in the TCOF1 gene have been detected.^[6] As a result of mutation of the TCOF1 gene, there is a defect in the production of nuclear phosphoprotein “Treacle.” This phosphoprotein is very much related to the proliferation and survival of cephalic neural crest cells. Various kinds of mutations such as insertions, deletions, and interpositions have been reported in various regions of the TCOF1 gene. Only 40% of cases show positive family predilection of this syndrome. The adult patient with features of TCS shows a convex facial appearance, an accentuated and prominent nose, hypoplastic mandible and underdeveloped chin, antimongoloid slanting of palpebral fissures, coloboma with hypoplasia of lower eyelids, and lateral canthi together with partial absence of eyelashes. Tongue-shaped hair process extending into the preauricular region, malformation of the external ear, impaired or decreased hearing ability due to hypoplasia of external auditory canals, and middle ear ossicles are prominent features of TCS. Often, due to constriction of the upper respiratory tract, respiratory distress may develop in some patients. In about 35% of cases, microstomia with a narrow palatal vault and cleft palate is seen.^[6] In this present case, cleft palate with anterior open bite was present. The cleft palate was repaired at 2 years of age of patient. Other dental anomalies such as supernumerary teeth, enamel opacity with hypoplasia, anodontia, microdontia, rotated tooth, and ectopic tooth are seen. Detailed patient history, thorough clinical extra and intraoral examination, and specialized imaging techniques such as lateral cephalogram, orthopantomogram, and CT scan may be performed for proper diagnosis and to assess the extent of craniofacial abnormalities.^[7] Jahrsdoerfer et al.^[8] stated that CT scan of the temporal bone in a TCS patient shows some radiographic findings such as absence of mastoid pneumatization, ossicular disjunction, and presence of bony cleft in the lateral aspect of the temporal bone and anterior to the mastoid. Literature review shows hypoplastic ear ossicles, hypoplastic epitympanum, and even in some cases, complete absence of the middle ear and external auditory canal. Molecular genetic testing should be done to detect mutations in TCOF1, POLR1C, and POLR1D genes.

There are various differential diagnoses of TCS such as Goldenhar syndrome, Miller syndrome, and Nager syndrome. Goldenhar syndrome includes hemifacial microsomia along with vertebral abnormalities unlike TCS. Miller syndrome exhibits additional features of ectropion of the lower eyelids. Nager syndrome involves malformation of the forelimbs along with facial abnormalities.

Ultrasound screening and anomaly scan during the mid-late gestation period help to detect severe abnormalities in a case of TCS. As far as the treatment of TCS patients is concerned, a multidisciplinary approach is required, which includes reconstructive maxillofacial surgery of cheekbones along with external ear prosthesis.^[9-11] Orthognathic surgery, distraction osteogenesis together with post-operative orthodontic management, not only helps to provide a good quality of life to a TCS patient but also gives a proper esthetic appearance and functional ability.^[9]

CONCLUSION

Dental practitioners must be aware of these manifestations and should be able to recognize the disorder. Early diagnosis and correct treatment planning with regular follow-up are required to provide the quality of life for the patient. Besides that, psychological counseling of both the patient and parents is required.