Treachear Collins Syndrome

Abstract

Treacher Collins syndrome, also known as Treacher Collins-Franceschetti syndrome, or mandibulofacial dysostosis is a rare autosomal dominant congenital disorder characterized by craniofacial deformities. Treacher Collins syndrome is found in about 1 in 50,000 births.. It is named after Edward Treacher Collins who described its essential traits in 1900. The cause of Treacher Collins Syndrome is a genetic mutation. TCOF1 is the only gene currently known to be associated with TCS, a mutation in this gene being found in 90-95% of the individuals with TCS. Mutation analysis has unveiled more than 100 disease-causing mutations in TCOF1, which are mostly family specific mutations.Keywords: Mandibulofacial dysostosis, Treacher Collins syndrome, Franceschetti syndrome Introduction Treacher Collins syndrome, alternatively called mandibulofacial dysostosis (MFD), is an autosomal dominant disorder of craniofacial development. It has been mapped to the gene on chromosome 5q32-q33.1. 6 It occurs with an incidence of 1 in 50,000 live births 4. Early descriptions are attributed to Berry (1889) 1, Treacher Collins (1900) (15) and Franceschetti and Klein (1949) 3. While 40% of TCS cases have a previous family history, 60% of cases possibly arise as a result of de novo mutations 7. From the structures affected and from studies in mice exposed to teratogenic cis- or trans-retinoic acid, it has been deduced that the disease results from interference in the development of the first and second branchial arches 4. Treacher Collin's syndrome results from a retardation/failure of differentiation of the maxillary mesoderm at the 50 mm stage of intrauterine development (at about 2 months)5. A defect in the stapedial artery during embryogenesis may be responsible for the anatomic defects seen. Stapedial artery dysfunction gives rise to defects of the stapes and incus and the first arch vessels supplying the maxilla. Failure of the inferior alveolar artery to develop an ancillary vascular supply gives rise to mandibular abnormalities11. Individuals have a convex profile with a prominent nose and retrusive chin. It is generally a bilateral anomaly with a characteristic facies, including downward sloping of the palpebral fissures, colobomas of the lower eyelids, mandibular and midface hypoplasia and deformed pinnas.10.12 Improper orientation and hypoplasia of the mandibular elevator muscles, resulting from an aplastic/hypoplastic zygomatic arch, may also be contributory. Mandibular retrognathia and midface vertical excess may be accentuated by the pull of abnormally oriented mandibular elevator muscles causing a backward rotation in the mandibular growth pattern. Great emphasis is placed on the genetic causes of Treacher Collin's syndrome, the specific gene associated has been identified as the 'Treacle gene' and has been located on the long arm of (q) of chromosome 5(5q32-33.1).2, 8 Recent animal experiments suggest a possible teratogenic role of hypervitaminosis A in the causation of facial defects in this syndrome. Case report An 8 year old boy reported to the Department of Pedodontics & Preventive Dentistry. The chief complaint was difficulty in eating due to presence of opening on the palate and malaligned teeth. The patient did not present history of any medical problems. He gave a history of surgical treatment of bilateral cleft lip. Extra oral examination revealed underdeveloped nose and zygomatic region, a retrognathic mandible. Decreased antero posterior lengths of neuro cranium, diminished bitemporal width were noted. He had a convex profile due to a severely retruded mandible. (Figure1A, 2A, 2B) Examination of the ears revealed malformed pinnae with flabby tissue and less amount of cartilage. (Figure3A, 3B) The patient presented with typical anti mongoloid slant of palpebral fissures, coloboma of the eyelids. Notching of outer part of lower eyelids (colobomas) was seen and a deficiency of the lower eyelashes (medial to colobomas) was present.(Figure3)There were bilateral atypical tongue shaped processes of the hairline (hairlick) extending towards the cheek. Intraoral examination revealed complete bilateral cleft of alveolus and hard palate. Inspection revealed solitary cleft of the premaxillary segment extending in a "v" pattern, bilaterally, mesial to 53, 63. Central tissue anastomosis adjacent to the labial vestibule and extending upto the vermillion border of upper lip was noted. Coronal third of 11, 21 were visible. Communication to the nasal cavity was appreciated on inspection. (Figure4,5) Occlusal radiograph of maxilla showed hazy converging radiolucencies mesial to 53, 63 region extending posteriorly upto mid palatal region adjacent to nasal septum. Conglomerate radiopaque mass resembling the permanent anteriors, showing ectopic eruption pattern was present. (Figure 6A) Lateral cephalogram shows severe protrusion of premaxillary segment, steep mandibular incline and enlarged paranasal sinuses. (Figure 6B) Orthopantomogram of the patient showed radiographically absent 12, 22, displaced permanent canines and multiple carious deciduous teeth. Suspected prominence of antigonial notch was also noted. (Figure 6C) Treatment From the time of birth, in severe cases the airway must be evaluated and secured. Either positioning alone or tracheostomy is required to manage the airway, and a gastrostomy for feeding. Operations of choanal atresia or mandibular lengthening are performed at the age of 2 to 3 years or later. To promote normal language development, cleft palate repair as well as evaluation by an otolaryngologist, audiologist and speech pathologist is recommended. Since the spectrum and degree of deformities related to TCS are extensive, a plan of management and timing of treatment needs to be tailored to the patient's specific problems. As a rule, bone reconstruction should precede soft tissue corrections. Autogenous tissues, such as calvarial (preferably vascularized) grafts, ribs and iliac bone should be used, while synthetic materials should be avoided. Although by 5 to 7 years of age the cranio-orbitozygomatic bone development is almost complete16, reconstructing before 10 years of age should be avoided. In order to minimize facial scarring, exposure for reconstruction of zygomatic and skeletal region is provided by a coronal (scalp) incision. Lateral canthopexies are completed during the same procedure. The lower face retrusion and increased facial convexity on profile are consistent features of TCS. Before facial growth is complete, chin augmentation and mandibular distraction are recommended. Definitive orthognatic surgery is delayed until the age of 16 to18 years. Most often the mandible advancement with bilateral sagittal ramus osteotomy, maxillary segmental osteotomies or a Le Fort I osteotomy to lower the posterior maxilla are performed, while Tessier's "integrale" procedure is reserved for severest cases14. The high-bridged nose can be improved by a classical rhinoplasty Coloboma of the lower eyelid is preferably corrected according to Tessier method (TESSIER 1976)13, which consists in Z-plasty for cutaneous lengthening, overlapping sutures of the preseptal orbicularis muscle and canthopexy. The preferred method of eyelid repair is the transposition of pedicled upper eyelid skin-muscle flaps to the lower eyelid deficient region (Z-plasty). Simultaneously the lateral canthi correction is performed to normalize the orbital area. Auricular reconstruction is one of the most difficult problems. The low-set auricular remnants, hairy skin and depressed area produce the main difficulties. Discussion According to a classification of craniofacial clefts, the complete form of the syndrome shows the presence of clefts 6, 7 and 813. The obligatory features are antimongoloid palpebral fissures, coloboma of lower eyelids, eyelash malformations, molar defects, preauricular hair displacement, micrognathia and "fishlike" facial appearance. The common features are macrostomia, auricular defects, high-arched palate, nasal deformity, malocclusion, open bite and deafness. Other abnormalities, such as cleft palate, colobomas of the upperlid, hypertelorism and mental retardation, are infrequent. In severely affected patients, the airway is compromised by the temporomandibular joint mandibular deficiency, glossoptosis and choanal atresia. Sleep apnea and sudden infant death syndrome are of particular significance. A unilateral form of TCS does not exist. The only syndrome that TCS resembles in its facial aspects is Nager's acrofacial dysostosis. The management of Treacher Collin's syndrome requires co-ordinated efforts of a team of specialists including pediatricians, surgeons, ENT specialists, speech therapists, oral surgeons and orthodontists to plan effective rehabilitation procedures.9 Due to the recent discovery of the defective gene that causes Treacher Collins, researchers are developing tests that will aid in more than accurate prenatal diagnosis of affected individuals. A prenatal diagnosis may be done by chorionic villus sampling at 10.5-12 weeks of pregnancy/ amniocentesis between 14 and 18 weeks, thus providing a chance to eliminate the gene from future generations' altogether. References * Berry G.A. (1889). Note On A Congenital Defect Colobomata Of The Lower Lid. R. Lond. Ophthalmic. Hosp. Rep. 12: 255. * Dixon Mj. Treacher Collins Syndrome. Hum Molec Genet 1996;1391-6. * Francheschetti A., Klein D. (1949). The Mandibulofacial Dysostosis: A New Hereditary Syndrome. Acta Ophthalmol. (Scand). 27: 143. * Gorlin R.J., Cohen M.M., Levin L.S. (1990). Syndromes Of The Head And Neck. Oxford University Press. Oxford. * Idem. The Pathogenesis Of The Treacher Collins Syndrome (Mandibulofacial Dysostosis). Br J Oral Surg 1975; 13:1. * Jabs E.W., Li X., Coss C.A., Taylor E.W., Meyers D.A., Weber J.L. (1991). Mapping The Treacher Collins Syndrome Locus To 5q31.3-Q33.3. Genomics. 11: 193-198. * Jones K.L., Smith D.W., Harvey M.A., Hall B.D., Quan L. (1975). Older Paternal Age And Fresh Gene Mutation: Data On Additional Disorders. J. Pediatr. 86: 84-88. * Neville, Damm, Allen, Bouquot. A Textbook Of Oral And Maxillofacialpathology. 2nd Ed. Saunders; 2002. P. 42-3. * Posnick Jc. Treacher Collin's Syndrome: Perspectives In Evaluation And Treatment. J Oral Maxillofac Surg 1997;55:1120-33. * Rajsekhar S, Govilla V, Mythili R. Treacher Collin's Syndrome: A Case Report. Ida 1998; 69:224-5. * Regezi Ja, Sciubba Jj. Oral Pathologic Correlations. W.B. Saunders Company; 1989. * Shafer Wg, Hine Mk, Levy Bm. A Textbook Of Oral Pathology. 4th Ed. Philadelphia Pa: Saunders; 1997. P. 681-2. * Tessier P. (1976). Anatomical Classification Of Facial, Craniofacial And Latero-Facial Clefts. J. Maxillofac. Surg. 4: 69. * Tessier P., Tulasne J-F. (1986). Cranial Surgery Update. In: Advances In Plastic And Reconstructive Surgery (Habal M.B., Ed.). Vol.2. Year Book Medical Publishers 30. * Treacher Collins E.T. (1900). Cases With Symmmetrical Congenital Notches In The Outer Part Of Each Lower Lid And Defective Development Of Malar Bones. Trans Ophthalmol. Soc. Uk. 20: 190.232 * Waitzman A.A., Posnick J.C., Armstrong D., Pron G.E. (1992). Craniofacial Skeletal Measurements Based On Computed Tomography. Part 2: Normal Values And Growth Trends. 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