27: Treacher Collins Syndrome: Evaluation and Treatment

Treacher Collins Syndrome

Evaluation and Treatment

Treacher Collins syndrome (TCS), which is also known as mandibulofacial dysostosis, is an autosomal dominant condition with variable expressivity.* It is generally characterized by bilaterally symmetric abnormalities of the structures within the first and second branchial arches. Early descriptions are attributed to Berry,10 Treacher Collins,51 and Franceschetti and Klein.41 To date, the physical findings of many hundreds of individuals and families with TCS have been published in the world literature.

The adult patient with fully expressed TCS has a convex horizontally deficient facial profile with a prominent nasal dorsum above a retrusive lower jaw and chin (Fig. 27-1). The eye region is characterized by an antimongoloid slant of the palpebral fissure as a result of colobomata and hypoplasia of the lower lids and the lateral canthi, including the partial absence of the eyelid cilia and inferolateral orbital hypoplasia and dystopia. Tongue-shaped processes of hair frequently extend into the preauricular region. The external ears are absent, malformed, or malposed and hearing is impaired as a result of variable degrees of hypoplasia of the external auditory canals and the ossicles of the middle ears. A characteristic finding is hypoplasia of the malar bones, often with clefting through the arches and limited formation of the residual zygomas, including the glenoid fossa component. The maxilla and mandible bones are also characteristically hypoplastic, with variable effects on the temporomandibular joints (TMJs), the muscles of mastication, and the muscles of facial expression. Interestingly, hypoplasia of the centrally located soft tissues of the face is not seen with TCS. In general, there is an Angle Class II anterior open-bite malocclusion and a steep clockwise-rotated maxillomandibular complex. The posterior facial height is short, and the anterior lower facial height is long. The A-point–to–B-point relationship in profile is consistent with the clockwise rotation of the jaws. The presence of cleft palate (with or without cleft lip and choanal atresia of the nasal cavity) is variable. Dental anomalies are present in 60% of individuals; these include tooth agenesis (33.3%), enamel opacities (20%), and the ectopic eruption of the maxillary first molars (13.3%).

Individuals with TCS have a reduced cranial base angle (i.e., basilar kyphosis). Craniosynostosis is not a feature of TCS, but the neurocranium may have an abnormal shape (i.e., decreased anteroposterior length and diminished bitemporal width) that is evident during childhood and remains through adulthood. 110 The degree of craniofacial malformation present at birth is believed to be relatively stable and non-progressive with age (this is discussed in more detail later in this chapter). TCS should not be confused with similar entities such as oculo–auriculo–vertebral dysplasia or Goldenhar syndrome. Distinguishing facial features of patients with TCS often include coloboma of the lower eyelids; the upper eyelids are more likely affected among patients with Goldenhar syndrome.

Inheritance, Genetic Markers, and Testing

The occurrence of TCS is in the range of 1 in 25,000 to 1 in 50,000 live births. Inheritance is autosomal dominant, and male and female individuals are equally affected.51 About 60% of probands with TCS have the disorder as the result of a de novo gene mutation. Each child of an individual with TCS has a 50% chance of inheriting the mutation (Fig. 27-2). Teber and colleagues identified TCOF1 mutations in 28 out of 36 (78%) individuals with a clinically unequivocal diagnosis of TCS.147 The most frequent clinical findings were downward-slanting palpebral fissures, hypoplasia of the zygomatic complex, hypoplasia of the mandible, conductive deafness, any degree of microtia, and atresia of the external ear canal. Although there were interfamilial and intrafamilial variations that ranged from mild to severe, there were no genotype or phenotype correlations. Four clinically unaffected parents were heterozygous for the TCOF1 mutation. The authors concluded that modifying factors are important for phenotypic expression.

Genetic counseling for TCS is the process of providing individuals and families with information about the nature, inheritance, and implications of the syndrome to help them make informed medical and personal decisions. Molecular testing should be considered for any individual who presents with at least two major features or three minor features of TCS.30,32,34,62,63,72,85,88,89,154,161,165 Until recently, penetrance in TCS was believed to be complete. Marres and colleagues confirmed the absence of clinical and radiographic findings in an individual with a pathogenic TCOF1 mutation. For this reason, testing is acceptable for individuals with any degree of severity of TCS features to confirm or refute the diagnosis.

Prenatal diagnosis for pregnancies that are at increased risk for TCS is possible via the analysis of DNA extracted from fetal cells obtained by amniocentesis; this is usually performed at about 15 to 18 weeks’ gestation. Chorionic villus sampling can also be used for diagnosis at about 10 to 12 weeks’ gestation. The malformation-causing allele of an affected family member must be identified before prenatal testing can be performed.

Considerations during Infancy and into Early Childhood

At the time of the birth of a child with TCS, concerns will center on the adequacy of the airway, swallowing, feeding, hearing, vision (corneal protection), the presence of cleft palate (with or without cleft lip), any other associated malformations, and the psychosocial well-being of the family.8,17,27,31,77,94,95,101,103,104,120,160 The airway may be compromised as a result of multiple factors. The first is maxillary hypoplasia, which occurs with a degree of choanal stenosis or atresia with the blockage of the nasal airway. Second, mandibular micrognathia with a retropositioned tongue that at least partially obstructs the oropharyngeal and hypopharyngeal spaces will be present. In addition, tracheomalacia, vocal cord anomalies, or neuromotor involvement may also negatively affect the upper airway. Depending on the severity of the anomalies, a spectrum of upper airway compromise may necessitate, at a minimum, special infant positioning, an extended hospital stay, and pulse oximetry monitoring. Surgical considerations for the management of airway compromise in the infant or young adult may include tongue–lip adhesion, the use of a custom-made oral appliance, immediate or delayed tracheostomy, or an urgent mandibular advancement procedure.

As a result of any compromise in nasal and oral breathing and associated musculoskeletal malformations, the newborn with TCS may also have difficulty with swallowing and with achieving an adequate lip seal to the extent that urgent gavage-assisted feedings or the placement of a gastrostomy tube may be required to ensure adequate nutrition.

When a cleft of the secondary palate is documented, potential additive effects on the airway before and after repair must be considered. When Nager syndrome is present, the soft palate is both clefted and severely hypoplastic to the extent that the achievement of a functioning palate is not feasible.65,96 A primary pharyngeal flap—although helpful for velopharyngeal function—is rarely indicated, because further obstruction of the airway would likely result. Evaluation by a medical geneticist is indicated to clarify the diagnosis and all presenting anomalies, to discuss family planning issues, and to analyze chromosomal studies.

Within a few days of birth, the results of an examination by an experienced pediatric otolaryngologist in combination with formal audiology testing will clarify the extent of conductive hearing loss and allow for the early fitting of hearing aids to assist the infant with the acquisition of communication skills and encourage the normal bonding process with the family.

At some point early in life, a complete craniofacial computed tomography (CT) scanning from the top of the skull through the cervical spine with three-dimensional reformation will be useful to document the extent of craniofacial skeletal anomalies. Special focused cuts through the petrous temporal bones are also required to document external auditory canal and middle and inner ear anatomy. Appropriate craniofacial, maxillofacial, cleft lip and palate, and auricular reconstructive surgeons should also be consulted, as indicated.

An assessment by a pediatric ophthalmologic is necessary to determine associated eye anomalies, extraocular muscle function, corneal exposure difficulties, and visual acuity. Ophthalmologic issues may include vision loss (37%), amblyopia (33%), refractive errors (58%), anisometropia (17%), and strabismus (37%). Interestingly, it has been the impression of many clinicians and scientists that the individual with TCS has a tendency toward a short stature, at least early in life, and that above-average intelligence is generally observed.

Dysmorphology with Treacher Collins Syndrome

Cranio–Orbito–Zygomatic Region

In earlier published studies, 14 reproducible cranio-orbito-zygomatic measurements taken from each of 26 standard axial CT scans of individuals with symmetric forms of TCS who had not been operated on were compared with the measurements of age-matched controls.110 The interorbital measurements (i.e., medial and lateral orbital wall separations) of the patients with TCS were at the mean when compared with their cohort group (i.e., no measurable orbital hypertelorism or hypotelorism), whereas the zygomatic measurements were significantly less than normal, thereby confirming the extent of malar hypoplasia. The congenitally deficient lateral aspect of the orbits in individuals with TCS was confirmed by the greater than normal values measured for globe protrusion and medial orbital wall protrusion in conjunction with diminished lateral orbital wall lengths. These measurements use the lateral orbital rim as a reference point and confirm the limited depth of the lateral orbits as a result of hypoplasia of the lateral orbital rims. The lateral orbital rims are components of the hypoplastic zygomatic complex. The abnormal shape of the anterior cranial vault in patients with TCS was documented as a diminished intercoronal (bitemporal) distance (width) and decreased cephalic length as compared with values for normal age-matched controls. In general, the CT measurements documented in the described study agree with the clinically observed morphology of TCS. The measurements carried out in the zygomatic structures confirmed the extent of hypoplasia of the zygomas for the group as a whole and in each individual patient; they also documented the extent of globe protrusion and decreased upper face width in patients with TCS. It appears as though the bones immediately adjacent to the involved zygomatic complex also experience a degree of hypoplasia or at least distortion.4,28,39,87,110,113,125,158,159,167,169

Maxillomandibular Region

In 1975, Roberts and colleagues completed a radiographic cephalometric study of TCS. Serial cephalometric radiographs were available for eight patients who presented with the full range of features that are characteristic of this syndrome.124 The expected facial convexity in patients with TCS was substantiated by cephalometric measurements. The extent of convexity was attributed to the severity of mandibular retrognathia (i.e., a decreased sella–nasion–B-point angle). Interestingly, the horizontal projection of the maxilla to the cranial base (i.e., the sella–nasion–A-point angle) remained within normal limits in the patients that were measured. Over time and with growth, the facial convexity remained relatively constant, thus confirming that the facial profile morphology of the infant with TCS was remarkably similar to that of the adult. Anterior facial heights were measured as “upper facial height” (i.e., the nasion to the anterior nasal spine) and “total facial height” (i.e., the nasion to the menton). The upper facial height was found to be relatively normal, whereas the total facial height was often excessive. This is the result of a combination of anterior open-bite malocclusion, mandibular retrognathism, and chin dysplasia characterized by increased vertical length and horizontal retrusion. The angle between the sella–nasion plane and the mandibular plane was obtuse, which confirmed the steepness of the clockwise rotation of the mandibular plane. The angle between the sella–nasion plane and the palatal plane was also obtuse, thus confirming the steepness of the clockwise rotation of the maxillary plane. The posterior facial height was markedly shorter for patients with TCS, with values in five of the eight patients found to be a minimum of four standard deviations less than those of the normal cohort.

The effective horizontal length of the mandible was markedly reduced, with values in most of the patients falling below four standard deviations as compared with those in the normal cohort. The decreased mandible size was evident in both the ramus height and the body length. The gonial angle was confirmed to be obtuse, with values of two standard deviations from the mean as compared with control values. The extent of antigonial notching was also documented in patients with TCS and was found to be similar to that observed among patients with condylar arrest early during their lives (e.g., as a result of juvenile rheumatoid arthritis or TMJ trauma at a young age). The steepness of the clockwise rotation of the maxillary and mandibular planes combined with the anterior and posterior vertical height disproportions and severe horizontal deficiency of the mandible is also indirectly seen in the A-point–to–B-point discrepancy. All of these morphologic findings explain the observed facial dysmorphology.4, 39,49,78,79,87

Facial Soft Tissues

Soft-tissue anomalies in individuals with TCS are manifested primarily in four clinical regions: the external ears; the eyelid–adnexal structures; the preauricular–cheek skin; and the temporal fossa (e.g., temporalis muscle hypoplasia).10,11,22,35,36,64,76,86,132,133,143,148,156 The extent of deficiency within the soft-tissue envelope is variable and, to large extent, reflective of the skeletal involvement. Each patient is unique and must be evaluated individually. The extent of soft-tissue anomalies continues to represent the most difficult obstacle to a favorable reconstruction.

External Auditory Canal, Middle and Inner Ear Structures, and Audiologic Findings

Relatively symmetric (i.e., from side to side) outer and middle ear malformations are characteristic of TCS. Middle-ear abnormalities (e.g., hypoplastic or absent cavities and ossicles) are an almost universal finding.18,55,58,66,118 The majority of patients have a unilateral or bilateral moderate or greater conductive hearing loss, with a flat or reverse sloping configuration on the audiogram. Most of the hearing loss in these patients is attributable to middle-ear malformations. In 1993, Pron and colleagues reported the results of a detailed CT radiologic and audiologic investigation of a large series of pediatric patients with TCS.118 The objectives of the study were 1) to determine the degree and symmetry of the external auditory canal and middle-ear abnormalities and evaluate hearing loss; and 2) to explore the relationship between hearing loss and external auditory canal and middle-ear abnormalities in patients with TCS. Data were available from 29 children who had not yet undergone any ear interventions and who had undergone audiometric testing and focused standardized petrous temporal bone CT scans. A review of the CT scans allowed for the evaluation of the external ear canal and the middle-ear anatomy. The majority of patients (88%) had largely symmetric external auditory canal abnormalities that were either stenotic (31%), atretic (54%), or normal (15%). Middle-ear cavity ossicular deformities were generally symmetric (96%), and cavities were either hypoplastic (85%) or missing (4%). Cavities that were hypoplastic were also deformed and assumed a rectangular rather than an oval shape. Ossicle deformities were generally completely symmetric and consisted largely of hypoplastic (46%) or missing (46%) ossicles. Ossicles (both the malleus and the incus) that were hypoplastic also tended to be ankylosed (82%) to either the lateral or medial wall of the tympanic recess. The structures of the external auditory canal and the middle ear are generally related. Increasing degrees of external ear canal malformations (i.e., normal, stenotic, or atretic) are directly associated with ossicle and cavity malformations. Of the patients with atretic canals, 67% had missing ossicles, and 33% had small or ankylosed ossicles. No abnormalities were noted in the inner-ear structures (i.e., cochlea, vestibule, canals, and internal auditory meatus) in the patients with TCS who were studied. According to the study by Pron and colleagues, hearing loss for the patient with TCS ranges from mild to severe (average, 58 dB of hearing loss).118 The majority of individuals (96%) have a moderate or greater degree of hearing loss.

Relationships exist between the external auditory canal, the middle-ear ossicles, and the degree and configuration of hearing loss.18,55,58,66,118 There is an association between the degree of external ear canal malformation and the degree of hearing loss in patients with TCS. In addition, hypoplastic, ankylosed, and missing ossicles appear to be associated with increasing levels of hearing loss; on average, the hearing loss is 52 dB, 56 dB, and 60 dB of hearing loss, respectively.

Facial Growth Potential with Treacher Collins Syndrome

The degree of malformation present at the time of birth in a newborn with TCS is believed to be relatively stable and non-progressive with age (Figs. 27-3 through 27-6).53,102,109,114,115,124 Roberts and associates reviewed serial cephalometric radiographs from individuals who were known to have TCS.124 They documented the stability of the mandible, which continued to grow but not to catch up. Through independent research, Garner reported findings of the cephalometric analysis of three patients of varied ages who were confirmed to have TCS.49 He also documented the relative stability of the anomalies without the progression of deformity at various ages.

To date, no convincing evidence demonstrates a clinically significant worsening of the TCS dysmorphology with facial growth. Early surgical interventions with mandibular osteotomies involving the use of either osteodistraction or standard orthognathic techniques are believed to adversely affect growth, thereby necessitating revision osteotomies at maturity. For this reason, waiting until the majority of jaw growth is complete before reconstructing the maxillomandibular components is recommended, if feasible. In any case, early mandibular surgery should not be expected to prevent the need for definitive maxillofacial reconstruction at maturity.

Classification of Temporomandibular Joint and Mandibular Malformation

The extent of TMJ–mandibular malformation in patients with TCS will influence the timing and techniques of reconstruction.69,137 A lack of clinically relevant definitions of the presenting glenoid fossa–condyle–ascending ramus malformations has resulted in confusion and miscommunication. Kaban and colleagues revised and clarified the previously described Pruzansky classification system for the degree of TMJ–mandibular malformation observed in patients with hemifacial microsomia.69,119 This classification is also useful to define the presenting anomalies and then to direct reconstruction in the patient with TCS (Fig. 27-7).

A Type I TMJ–mandibular malformation involves minimal hypoplasia of the glenoid fossa and the condyle–ascending ramus on each side. All of the skeletal components are present (see Fig 27-7, A). Mandibular retrognathia and a mild anterior open bite are likely to be present, but TMJ function is essentially normal. The muscles of mastication are intact, and the condyle and the glenoid fossa are also fully intact. There is no need or advantage to constructing a neo-condyle or neo-glenoid fossa.

A Type IIA TMJ–mandible malformation involves a moderate degree of glenoid fossa and condyle–ascending ramus hypoplasia (see Fig. 27-7, B, C, and D). The anatomic location of each joint is anterior and medial, but TMJ function remains satisfactory. One or more of the paired muscles of mastication are likely to be hypoplastic. By definition, in Type IIA malformations, the condyle and the glenoid fossa have function that is at a level deemed better than could reliably be achieved through TMJ replacement. Even in patients with more severe Type IIA malformations, when applying superior and posterior pressure to the chin, the condyles can be seated into a consistent location against the skull base–glenoid fossa. By completing ramus osteotomies, the proximal segments can be positioned into a stable location against the skull base, and the distal mandible can then be reoriented into the preferred location. This will avoid the need to construct neo-condyles (e.g., costochondral grafts). Coronoidectomies may be required to accommodate the short condyles.

The Type IIB TMJ–mandibular malformation involves severe hypoplasia of the condyles. The mandible is without a stable centric relation. The glenoid fossa may be hypoplastic, but they are deemed functional. The hypoplastic condyles do not consistently seat in the glenoid fossa, and the mandible functions within a limited range of motion. The extent of mandibular retrognathia and anterior open bite is marked. With Type IIB TMJ–mandibular malformations, the rudimentary condyles are deemed too far medially and anteriorly displaced to be useful. The construction of a neo-condyle ascending ramus with the use of a bone graft is required (see discussion to follow). Coronoidectomies and recontouring of the surgically advanced mandible may be required. Fortunately, this pattern of malformation occurs in only a small percentage of patients with TCS.

The Type III glenoid fossa–mandibular malformation involves deficiency to the extent that no posterior stop of the lower jaw against the cranial base is possible (see Fig. 27-7, E). The condyles and the ascending rami are not present. The disc, the TMJ capsule, and the glenoid fossa on each side are also not developed. Severe mandibular dysmorphology is present, including horizontal retrognathia and decreased posterior ramus height. A tracheostomy is generally required shortly after birth to manage the airway. Eventual construction of both a neo-glenoid fossa and a neo-condyle ascending ramus will be required on each side. Reconstruction with bone grafts (e.g., cranial grafts for the zygomatic complex and either costochondral or a vascularized fibula flap for the mandible) will be required (see discussion to follow).

Staging of Skeletal Reconstruction: Timing and Techniques

The reconstruction and rehabilitation of the Treacher Collins malformation must address unique and specific components of the anomalies, including the following: 1) the zygomatic and orbital region; 2) the maxillomandibular region; 3) the nasal region; 4) the soft-tissue envelope; 5) the external ears; 6) the external auditory canals; and 7) the middle-ear structures (Figs. 27-8 through 27-10).*

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Figure 27-9 Additional images of the patient from Fig. 27-8 showing the stigmata of Treacher Collins syndrome. At the age of 17 years, the patient was referred to this surgeon and agreed to a staged reconstruction that included three operations. The initial preoperative orthodontic treatment included the extraction of mandibular first premolars with the retraction of the anterior dentition to remove compensations. Orthognathic surgery included a Le Fort I osteotomy (counterclockwise rotation and anterior maxillary intrusion); bilateral sagittal split ramus osteotomies (advancement and counterclockwise rotation); and an osseous genioplasty (vertical reduction and advancement). During a second operation, the patient underwent zygomatic complex reconstruction with fixed full-thickness autogenous cranial bone grafts as described in this chapter and as illustrated in Fig. 27-8. This was followed a third operation: septorhinoplasty (open approach) to in-fracture the nasal bones, reduce the dorsal hump (bone and cartilage), and reshape the tip, including septal (caudal strut) grafting (see Chapter 38). A, Right profile views before and after reconstruction. B, Left profile views before and after reconstruction. C, Lateral cephalometric radiographs before and after reconstruction. D, Articulated dental casts that indicate analytic model planning. E, Occlusal views before treatment, early after reconstruction, and 3 years after reconstruction. A degree of maxillary relapse (skeletal versus dental) has occurred but with a retained functional occlusion and favorable facial aesthetics. F, Crafted autogenous cranial grafts shown before and then after inset into the zygomatic defects. The advancement of the hypoplastic temporalis muscles is also demonstrated. The soft-tissue hypoplasia involves multiple layers (i.e., skin, subcutaneous tissue, fascia, and fat tissue) and therefore can not be fully corrected simply by advancing the hypoplastic temporalis muscle. G, Axial computed tomography scan views shown through the zygomas before and after malar reconstruction indicating the improved interzygomatic buttress width, interzygomatic arch width, and zygomatic arch length. A, From Posnick JC, Treacher Collins syndrome: Perspectives in evaluation and treatment, J Oral Maxillofac Surg 55:1120, 1997. F (bottom left, bottom right), G, From Posnick JC, Goldstein JA, Waitzman A: Surgical correction of Treacher Collins malar deficiency: quantitative CT scan analysis of long-term results, Plast Reconstr Surg 92:12, 1993.

Jan 1, 2015 | Posted by in Orthodontics | Comments Off on 27: Treacher Collins Syndrome: Evaluation and Treatment
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