New grading system for patients with treacher Collins syndrome

Treacher Collins syndrome (TCS) is a congenital, craniofacial disorder affecting the development of structures derived from the first and second branchial arches. The associated clinical features and their severity are variable. Therefore, we reasoned that objective assessment of the clinical features and their severity in TCS is necessary to plan the treatment and to evaluate the outcome. We hereby propose a new grading system for Treacher Collins syndrome (TCS). Since 1978, 16 patients have been diagnosed with TCS. Eleven out of the 16 TCS patients, for whom we were able to estimate the severity of the clinical features in each region, and to make an objective assessment of the therapeutic outcomes, were selected. By allocating points according to the degree of severity of the clinical features in each region, then summing them up and categorizing them, we classified the overall clinical features into 3 grades. The severity increases from grades I to III. In summary, there were 3 patients of grade I, 4 patients of grade II and 4 patients of grade III. Distinctive differences regarding the degree of severity of the clinical features were clearly observed between each grade. We propose a new TCS grading system and applied it to 11 patients. We believe that this system may be useful for planning treatment and to evaluate the outcome in TCS patients.     

Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development which results from loss-of-function mutations in the gene TCOF1. TCOF1 encodes the nucleolar phosphoprotein, Treacle, which plays a key role in pre-ribosomal processing and ribosomal biogenesis. In mice, haploinsufficiency of Tcof1 results in a depletion of neural crest cell precursors through high levels of cell death in the neuroepithelium, which results in a reduced number of neural crest cells migrating into the developing craniofacial complex. These combined advances have already impacted on clinical practice and provide invaluable resources for the continued dissection of the developmental basis of TCS.     

Increased fistula risk following palatoplasty in Treacher Collins syndrome.

OBJECTIVE: Patients with Treacher Collins syndrome have abnormal vascular supply to the palate, yet it is unknown whether there are increased postoperative healing problems following palatoplasty. This study investigated the correlation between Treacher Collins syndrome and postoperative palatal fistula formation. DESIGN: Retrospective chart review was performed. PATIENTS: Children undergoing palatoplasty at Children's Hospital Los Angeles from 1987 to 2000 were evaluated. Ten children with Treacher Collins syndrome, 92 children with other syndromes and cleft palate, and 458 nonsyndromic patients with isolated cleft palate were studied. INTERVENTIONS: All children were treated with a one-stage, double-reversing Z-plasty cleft palate repair. MAIN OUTCOME MEASURES: Outcome measures included intraoperative observations of surgical anatomy and postoperative clinic follow-up of fistula formation. Palatal fistula rates between patients with Treacher Collins syndrome, other syndromes, and no syndrome were compared with chi-square analysis. RESULTS: Children with Treacher Collins syndrome had significantly greater palatal fistula rates (50%) than children with other syndromes (8.7%) or no syndrome (4.1%). Treacher Collins patients demonstrated large palatal fistulas and poor flap vascularity. CONCLUSIONS: Children with Treacher Collins syndrome and cleft palate have significantly higher palatal fistula risk than other children with cleft palate when double-reversing Z-plasty palate repair is performed. Our findings suggest that children with Treacher Collins syndrome and cleft palate may have poor vascularity to palatal flaps created during palatoplasty. Furthermore, we recommend that surgeons performing palatoplasty minimize the dissection of mucoperiosteal flaps around the greater palatine arterial pedicle and utilize closure techniques creating the least vascular disruption of palatal tissue.     

Prosthetic management of a patient with Treacher Collins syndrome.

Treacher Collins syndrome encompasses a group of closely related defects of the head and neck. It is a rare syndrome characterized by bilaterally symmetrical abnormalities derived from the first and second brachial arches and the nasal placode. It is an autosomal dominant disorder and its occurence ranges from 1 in 25,000 to 1 in 50,000 live births. The facial appearance of these patients can be improved by either surgical or prosthetic rehabilitation. In this case report we are presenting the features of a 13-year-old boy with Treacher Collins syndrome. A multidisplinary approach was followed in managing the situation. The various treatment options and the steps involved in making an auricular prosthesis are also discussed.     

Treacher Collins syndrome: comprehensive evaluation and treatment

When contemplating the reconstructive options for patients with Treacher Collins syndrome, surgeons must recognize the complex interplay between growth of the craniofacial region and the possible effects of early surgery on further growth. Consequently, surgical procedures for the deformities in Treacher Collins syndrome are staged based on the dysmorphology and the growth velocity of each anatomic region. This article reviews the evaluation and management considerations for patients with Treacher Collins syndrome.     

The surgical management of Treacher Collins syndrome

Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti–Zwahlen–Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard and soft tissues of the first and second branchial arches. Early operations focus on maintaining the airway, protecting the eyes, and supporting auditory neurological development. Later operations include staged reconstruction of the mouth, face, and external ear. Bimaxillary surgery can improve the maxillomandibular facial projection, but correction of malar, orbital rim, and temporal defects may be more difficult. We present a clinical review of the syndrome with a chronological approach to the operations.     

Craniofacial morphology in Treacher Collins syndrome

Treacher Collins syndrome is a rare but well studied autosomal dominant craniofacial malformation syndrome. Most reports to date have focused on the facial morphology of this distinctive syndrome, but several more recent investigations have described abnormalities of the basicranium, mandible, and upper airway. The purpose of this report is to describe craniofacial morphology in a sample population of 12 patients with Treacher Collins syndrome. A special emphasis is placed on cranial base and mandibular structure because of the airway problems often encountered in this syndrome.     

Distraction osteogenesis of zygomatic bone grafts in a patient with Treacher Collins syndrome: a case report

Zygomatic aplasia in patients with Treacher Collins syndrome requires reconstruction with autogenous bone grafts. Serial bone grafting may be required if optimal malar projection is not achieved with the initial procedure. This report demonstrates the use of distraction osteogenesis in repositioning a previously bone-grafted zygoma in an adolescent patient with Treacher Collins syndrome, thus avoiding the need for repeat bone graft harvest. The limitations of this technique include difficulty in achieving the desired vector of distraction and the potential of graft devitalization. Nevertheless, the case report illustrates the versatility of distraction osteogenesis in skeletal augmentation/remodeling.     

Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause

This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.     

Cervical spine in Treacher Collins syndrome

Treacher Collins syndrome is a congenital syndrome with characteristic craniofacial malformations, which are well described in the literature. However, the presence of cervical spine dysmorphology in this syndrome has been minimally described. This study reviews cervical spine radiographs of 40 patients with Treacher Collins syndrome. In this sample, 7 of 40 patients displayed cervical spine anomalies, with 3 of these patients displaying multiple cervical spine anomalies. The patterns of spinal anomalies were variable, suggesting that the underlying genetic mutation has variable expressivity in cervical spine development as it does elsewhere in the craniofacial skeleton.     

Computer-assisted midface reconstruction in Treacher Collins syndrome part 2: Soft tissue reconstruction

IntroductionTreacher Collins syndrome (TCS) midfacial involvement associate a skeletal hypoplasia centred on the zygoma to a hypoplasia of all surrounding soft tissues layers and an inferolateral lower lid pseudocoloboma. TCS soft tissue hypoplasia, which has not been well studied, continues to bring challenges in both the indication of surgical treatment and the prediction of their results.Material and methodFrom a standard magnetic resonance imaging (MRI) acquisition, we studied qualitatively and quantitatively the prezygomatic fat compartments and the buccal fat pad of two individuals with TCS whose age were 10 and 14 years. In parallel, we studied 20 controls at the same age to obtain a morphometric database of reference and compare our results. TCS soft tissue involvement was correlated to the results of our prior skeletal involvement study.ResultsThe midfacial fat compartments in TCS are severely hypoplastic, especially in the superficial and lateral compartments of the face (all P's < 0.001). No significant correlation existed between the soft tissue and the skeletal involvement.ConclusionsTo our knowledge, this is the first published study of TCS midfacial fat compartments. Their hypoplasia is an important part of the syndrome's facial deformity. The knowledge of their anatomy, organization and volumetric variation is essential. Their re-establishment is key in the early treatment phases of this syndrome. Using the preoperative data, the morphometric database of reference, and surgical simulation, an appropriate surgical technique, going from an autologous fat graft to a free flap, can then be chose.     

Clinical and imaging correlations of Treacher Collins syndrome: report of two cases

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.     

Orbital volume and shape in Treacher Collins syndrome

Orbito-palpebral reconstruction is a challenge in Treacher Collins syndrome (TCS). This study investigates orbital phenotypes in TCS using cephalometry and orbital shape analysis.Eighteen TCS and 52 control patients were included in this study, using the Dr Warehouse database. Orbital cephalometry was based on 20 landmarks, 10 planes, 16 angles, and 22 distances. Orbits were segmented. Registration-based, age-specific mean models were generated using semi-automatic segmentation, and aligned and compared using color-coded distance maps – mean absolute distance (MAD), Hausdorff distance (HD), and Dice similarity coefficient (DSC). Symmetry was assessed by mirroring and DSC computing.Central orbital depth (COD) and medial orbital depth (MOD) allowed 100% of orbits to be classified. COD and lateral orbital depth (LOD) were different from the controls. Average MAD between TCS and controls was ≤1.5 mm, while for HD it was >1.5 mm, and for DSC <1. TCS orbits were more asymmetrical than controls, and orbital volumes were smaller when age was considered as a confounding factor, and had a trend for normalization with age.This report emphasizes the importance of combining different morphometric approaches in the phenotype characterization of non-trivial structures such as the orbit, and supports composite skeletal and soft-tissue strategies for the management of the peri-orbital region.     

Pathogenesis of cleft palate in Treacher Collins, Nager, and Miller syndromes

Abnormalities of the secondary palate were studied in an animal model in which features of Treacher Collins syndrome (TCS) and Nager or Miller syndromes (both of which are facially similar to Treacher Collins, but include limb malformations) were induced by acute maternal exposure to 13-cis-retinoic acid (13-cis-RA, isotretinoin, Accutane). Previous work in our laboratory has illustrated that excessive cell death in the proximal aspect of the maxillary and mandibular prominences of the first visceral arch and in the apical ectodermal ridge of the limb bud probably accounts for the characteristic craniofacial and limb abnormalities observed (Sulik et al, 1987; Sulik and Dehart, 1988). The current study shows that maternal treatment with 400 mg per kilogram 13-cis-RA at 8 days 14 hours (8d14hr) or 9d6hr post fertilization results in abnormalities of the secondary palate that vary in incidence and severity. Following the earlier treatment time, 82 percent (68 of 74) of the 18d fetuses were affected, with, severely hypoplastic, unfused palatal shelves present in 34 percent (25 of 74). The less severely affected fetuses had malformations that involved primarily the posterior aspect of the palatal shelves. This malformation (foreshortening of the posterior portion of the palate) constituted the major developmental alteration that resulted from treatment at the later time, at which time a 52 percent (26 of 50) malformation incidence was seen. The change in pattern of malformations with treatment time is consistent with the changing pattern of programmed cell death, which was observed to occur in the first visceral arch.     

Adolescents' perspectives on living and growing up with Treacher Collins syndrome: a qualitative study.

OBJECTIVE: This study explored the experiences and essences of growing up and living with Treacher Collins syndrome (TCS) from an adolescent perspective. DESIGN: A qualitative approach using the long interview method was used to explore the adolescents' experiences. Semistructured interviews and peer debriefing techniques were used to gather and verify data with each participant. PARTICIPANTS: A purposive sampling technique was used to recruit a sample of six adolescents with TCS, ranging in age from 12 to 18 years, who received care from a craniofacial center in a large pediatric hospital. RESULTS: The themes central to the adolescents' experiences were balancing sameness and difference and the journey toward social and self-acceptance. Five subthemes further described this experience: reconstructing perceptions of others; making meaning of the difference; forming friendships and fitting in; handling staring and teasing; and excelling. CONCLUSIONS: The study group described good psychosocial adjustment, experienced an increasing acceptance of self, TCS, and social acceptance over time and demonstrated resilient adaptive strategies (optimism, motivation, and positive meaning making). They were, however, also challenged by the social stigma associated with difference and by the challenges of finding a good fit in their school environments in meeting unique needs, particularly in their early grades. This study highlights the value of using a qualitative research approach in furthering our understanding of the experiences of children and youth with facial differences.     

Genetic craniofacial aberrations

Many craniofacial and dental anomalies have a genetic background. Much research related to the molecular pathology of genetic conditions is being carried out, and new information related to mapping of disease genes, gene identification, and mutations in these genes is accumulating with incredible speed. It is important to be well informed of the molecular background of the conditions that we treat at anomaly clinics. This article reviews the most recent molecular findings related to Turner syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome, Treacher Collins syndrome, cleidocranial dysplasia, and cleft lip and palate.     

Retrograde fiberoptic technique to avoid tracheostomy in a patient with a tracheocutaneous fistula and Treacher Collins syndrome

Children with Treacher Collins syndrome have multiple craniofacial abnormalities that can cause difficulty ventilating and intubating under general anesthesia. We describe a unique technique to secure an endotracheal tube via a retrograde technique using patent tracheocutaneous fistula and fiberoptic bronchoscopy. In this setting, the presence of a tracheocutaneous fistula spared tracheostomy in this patient.     

Mandibulofacial dysostosis. Case report

A case of mandibulofacial dysostosis (Treacher Collins syndrome) is presented. Clinical features and skull radiographs revealed typical anomalies associated with the syndrome. Cleft of the soft palate and unerupted multiple supernumerary teeth were present in this case. No haematological, biochemical or immunological abnormalities could be detected in the patient. Pedigree analysis showed an autosomal dominant mode of transmission of the disease. Chromosomal studies did not reveal any structural or numerical discrepancies.     

Nager acrofacial dysostosis: early intervention and long-term planning.

Nager acrofacial dysostosis is an extremely rare syndrome combining craniofacial features similar to Treacher Collins mandibulofacial dysostosis with the additional features of thumb and radial bone hypoplasia. The clinical and prognostic aspects of two unrelated infants with Nager acrofacila dysostosis are presented. A vigorous early intervention program of habilitation is described with emphasis on the facilitation of speech and language development in children with multiple morphological and developmental problems.     

Computer-assisted midface reconstruction in Treacher Collins syndrome part 1: Skeletal reconstruction

IntroductionTreacher Collins syndrome (TCS) is a severe and complex craniofacial malformation affecting the facial skeleton and soft tissues. The palate as well as the external and middle ear are also affected, but his prognosis is mainly related to neonatal airway management. Methods of zygomatico-orbital reconstruction are numerous and currently use primarily autologous bone, lyophilized cartilage, alloplastic implants, or even free flaps. This work developed a reliable “customized” method of zygomatico-orbital bony reconstruction using a generic reference model tailored to each patient.MethodsFrom a standard computed tomography (CT) acquisition, we studied qualitatively and quantitatively the skeleton of four individuals with TCS whose age was between 6 and 20 years. In parallel, we studied 40 controls at the same age to obtain a morphometric database of reference. Surgical simulation was carried out using validated software used in craniofacial surgery.ResultsThe zygomatic hypoplasia was very important quantitatively and morphologically in all TCS individuals. Orbital involvement was mainly morphological, with volumes comparable to the controls of the same age. The control database was used to create three-dimensional computer models to be used in the manufacture of cutting guides for autologous cranial bone grafts or alloplastic implants perfectly adapted to each patient's morphology. Presurgical simulation was also used to fabricate custom positioning guides permitting a simple and reliable surgical procedure.ConclusionsThe use of a virtual database allowed us to design a reliable and reproducible skeletal reconstruction method for this rare and complex syndrome. The use of presurgical simulation tools seem essential in this type of craniofacial malformation to increase the reliability of these uncommon and complex surgical procedures, and to ensure stable results over time.