Impact of protraction or orthognathic surgery for class III malocclusion on longitudinal quality of life in patients with cleft lip and palate.

OBJECTIVES: This study assessed overall quality of life (QoL) over time in youth with cleft lip and palate (CLP) undergoing maxillary protraction treatment or orthognathic surgery for class III malocclusion to identify any differences in QoL based on treatment group and outcome success. MATERIALS AND METHODS: A prospective longitudinal cohort study was conducted in two pediatric hospitals. The Short Form Health Survey (SF-12) measured physical and mental QoL prior to treatment, at maximal correction, at treatment completion, and at 1-year post treatment. Analyses included one-sample, two-sample, and paired t-tests and analyses of variance and covariance. RESULTS: Participants (N = 91) either completed protraction (n = 53) at age 11-14 or surgery (n = 38) at age 16-21. Participants were mostly Latinx (67%) males (55%) born with unilateral CLP (81%) and there were no demographic differences between the two groups other than age. The total sample's QoL was in the average range and significantly higher than national norms. No significant differences were found in QoL-based outcome success; however, the protraction group showed a gradual physical QoL improvement over time, while the surgery group experienced a temporary drop in physical QoL postoperatively. At treatment completion, higher physical QoL was associated with higher socioeconomic status. At a year post treatment, mental QoL was significantly higher for males. CONCLUSION: Both protraction and surgery appear to be acceptable treatment options in terms of overall QoL for youth with CLP. While treatment success did not impact QoL, there were some differences in physical QoL coinciding with the treatment phase as well as individual factors.

Does Distraction Lower Risk of VPI Compared to Conventional Maxillary Advancement? A Retrospective Cohort Study of Adolescents with Cleft Palate.

OBJECTIVE: To determine whether method of maxillary advancement in adolescents with cleft palate with or without cleft lip (CP ± L) influences post-operative velopharyngeal function. DESIGN: Retrospective cohort. SETTING: Pediatric Tertiary Care Hospital. PARTICIPANTS: One hundred and ninety-nine patients with CP ± L after LeFort I osteotomy for maxillary advancement at our institution between January 2007 and June 2019. INTERVENTIONS: LeFort I osteotomy via distraction osteogenesis (DO) or conventional osteotomy (CO). MAIN OUTCOME MEASURES: Patients who underwent DO or CO were compared for the presence of new velopharyngeal insufficiency (VPI), as measured by perceptual rating by a craniofacial speech-language pathologist.Of the 199 patients who underwent maxillary advancement, 126 were available for analysis. The DO group was younger, male, and had more severe maxillary hypoplasia. Following surgery, 17/41 (41.5%) of the DO group had new VPI, compared to just 23/85 (27.1%) of the CO group. After adjusting for cleft type and predicted maxillary advancement, however, there was not sufficient evidence to reject the null hypothesis of no difference in risk of post-operative VPI between the two surgical groups (prevalence ratio [PR] 1.40, 95% CI 0.68-2.90). Increased prevalence of VPI after DO versus CO was primarily observed among patients with a pre-operative velopharyngeal need ratio < 0.8 (PR = 2.01, 95% CI 0.79-5.10) and patients with normal velopharyngeal function pre-operatively (PR = 2.86, 95% CI 0.96-8.50).Our results suggest an increased rather than decreased risk of VPI following DO relative to CO. This association is primarily seen among those with a smaller velopharyngeal ratio or perceptually normal velopharyngeal function pre-operatively.

Le Fort II Distraction With Zygomatic Repositioning: A Technique for Differential Correction of Midface Hypoplasia.

Severe midface hypoplasia is frequently addressed with subcranial midface advancement at the Le Fort II or Le Fort III level. Le Fort II advancement has a predominant affect on the vertical and sagittal positioning of the nasomaxillary complex; in contrast, the Le Fort III advancement allows for correction of zygomatic position and exorbitism. In this report, the authors described a technique for correction of exorbitism which concomitantly addresses central midface vertical and sagittal deficiency. The technique involves a combination of a Le Fort III osteotomy with a Le Fort II distraction. The Le Fort III osteotomy allows repositioning and fixation of the zygomas to correct lateral hypoplasia and exorbitism, maintaining the globes in a more functional position. The Le Fort II distraction allows for movement of the central midface independent of the lateral orbits and zygomas, correcting the sagittal and vertical position without orbital distortion. With the medial canthal apparatus attached to the Le Fort II segment and the lateral canthus attached to the stabilized lateral orbits, the differential movement achieved can also have a favorable effect on palpebral fissure orientation.

Distraction Osteogenesis Normalizes Mandibular Body-Symphysis Morphology in Infants With Robin Sequence.

PURPOSE: To evaluate changes in mandibular morphology in infants with Robin sequence (RS) after mandibular distraction osteogenesis (MDO) and compare the post-distraction morphology with that in infants without RS and infants with RS who had not undergone MDO. MATERIALS AND METHODS: Infants with RS treated with MDO were retrospectively evaluated over a 12-year period. All patients had pre-distraction and end-consolidation maxillofacial computed tomograms. Morphologic features of the mandible were divided into ramus and condyle, body and symphysis, and composite measurements. Post-distraction RS mandibular morphology was compared with pre-distraction morphology, as well as to age-matched infants without RS and age-matched infants with RS who had not undergone MDO. Comparisons were done using nonparametric paired-samples analyses. RESULTS: During the study period, 17 patients with RS treated with MDO met the inclusion criteria for the study. The mean ages at distraction and end-consolidation were 1.95 ± 3.24 and 8.46 ± 5.99 months, respectively. The post-MDO mandible was significantly different from the pre-MDO mandible with regard to the ramps-condyle unit and body-symphysis measurements, including development of a more parabolic mandibular arch form (P ≤ .001). Compared with age-matched non-RS infant mandibles, the post-distraction RS mandibles had similar morphologies. Compared with age-matched non-MDO RS mandibles, the post-distraction mandibles had significantly different morphologies anterior to the gonial angle, including a more parabolic arch form (P ≤ .006). CONCLUSIONS: MDO normalized mandibular morphology in infants with RS, with the greatest effect on measurements anterior to the gonial angle.

Defining mandibular morphology in Robin sequence: A matched case-control study.

Robin Sequence (RS) is classically defined as the triad of micrognathia, glossoptosis, and airway obstruction. While there remains significant debate over diagnostic criteria for severity, there is consensus regarding micrognathia as a defining feature of the condition. The purpose of this study was to compare mandibular morphology among infants and children with RS to infants and children without RS using maxillofacial computed tomography. Our hypothesis was that there are discrete morphologic differences between RS and non-RS mandibles. Our goal was to determine if there are defined and measureable differences in RS mandible shape that can be used in defining the sequence. We identified 20 cases with RS and 20 age- and sex-matched controls without RS. Linear, angular, and composite measurements were obtained for each patient. Cases had shorter mandibular sagittal lengths (-27%, p = 0.001), shorter inferior border arc lengths (-11.5%, p = 0.002), steeper gonial angles (+10.5%, p < 0.001), and narrower symphyseal angles (-11.5%, p < 0.001). Mandibular shape in RS was more rounded/elliptical (p < 0.001) and infants with RS had a significantly smaller submental cross-sectional area (-29.4%, p < 0.001). These shape differences anterior to the gonial angle of the mandible appear to be a defining morphologic feature in RS.

Cephalometric assessment of craniofacial morphology in patients with treacher Collins syndrome.

BACKGROUND AND PURPOSE: Treacher Collins syndrome is an autosomal dominant craniofacial disorder affecting derivatives of the first and second branchial arches. Given the conflicting reports in the literature regarding the extent of anterior-posterior and vertical (superior-inferior) dysplasia of the cranial base, maxilla, and mandible, this study was designed to provide a comprehensive lateral cephalometric assessment of the craniofacial morphology of unoperated patients with Treacher Collins syndrome. METHODS: The records of 45 patients with Treacher Collins syndrome registered at the Institute of Reconstructive Plastic Surgery of the NYU Langone Medical Center from the period of 1975 to 2008 were reviewed. Inclusion criteria included (1) patients between with the ages of 5 and 17 years, (2) no history of prior surgical intervention to correct skeletal deformity, and (3) diagnostic quality lateral cephalograms. Twenty patients satisfied the inclusion criteria with 12 male and 8 female patients in the sample and a mean age at the time of the lateral cephalogram of 8.8 years (range 5.2 to 16.7 years). Thirty angular and linear variables were measured to assess anterior-posterior and vertical (superior-inferior) position of the cranial base, maxilla, and mandible. Each patient's measurements were compared to age-matched and sex-matched control samples derived from the Moyers growth studies. The mean and standard deviation for each variable was then determined. RESULTS: Lateral cephalometric analysis showed decreased anterior, posterior, and total cranial base lengths and a reduced cranial base angle. The anteroposterior dimension or length of the maxilla is deficient and the maxilla is positioned posteriorly with respect to the cranial base. Both anterior and posterior facial heights (superior-inferior dimension) are decreased. Lower face height is increased, whereas total face is decreased. The maxillary and functional occlusal planes are tipped upwards posteriorly. The mandibular morphology is characteristically small in both body length and total mandibular length, and the maximum ramus width is also deficient. The mandibular plane angle and gonial angle are increased. The mandible is retropositioned. CONCLUSIONS: A lateral cephalometric analysis is described that provides a skeletal basis for the hallmark clinical findings associated with Treacher Collins syndrome. This is of importance because an understanding of the underlying skeletal dysmorphology may shed light on the etiology and growth pattern, and impacts the overall treatment planning for skeletal correction.

Craniofacial Growth and Development: A Primer for the Facial Trauma Surgeon.

Understanding craniofacial growth and development is important in the management of facial trauma in the growing pediatric patient. This manuscript is a review of craniofacial growth and development and clinical implications of pediatric facial fractures.

Subcranial Midface Advancement in Patients with Syndromic Craniosynostosis.

Patients with syndromic craniosynostosis can present with midface hypoplasia, abnormal facial ratios, and obstructive sleep apnea. These symptoms can all be improved with midface advancement, but it is essential to evaluate the specific morphologic characteristics of each patient's bony deficiencies before offering subcranial advancement. Midface hypoplasia in Crouzon syndrome is evenly distributed between the central and lateral midface and reliably corrected with Le Fort III distraction. In contrast, the midface hypoplasia in Apert/Pfeiffer syndromes occurs in both an axial and a sagittal plane, with significantly more nasomaxillary hypoplasia compared with the orbitozygomatic deficiency.

Orthognathic Surgery in Patients with Syndromic Craniosynostosis.

Patients with syndromic and nonsyndromic synostosis may have end-stage skeletal discrepancies involving the lower midface and mandible, with associated malocclusion. While orthognathic surgical procedures in this population can be reliably executed, the surgeon must be aware of the unique morphologic characteristics that accompany the primary diagnoses as well as the technical challenges associated with performing Le Fort I osteotomies in patients who have undergone prior subcranial midface distraction.

Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.

Mutations in the paired-domain transcription factor PAX9 are associated with non-syndromic tooth agenesis that preferentially affects posterior dentition. Of the 18 mutations identified to date, eight are phenotypically well-characterized missense mutations within the DNA-binding paired domain. We determined the structural and functional consequences of these paired domain missense mutations and correlated our findings with the associated dental phenotype variations. In vitro testing included subcellular localization, protein-protein interactions between MSX1 and mutant PAX9 proteins, binding of PAX9 mutants to a DNA consensus site and transcriptional activation from the Pax9 effector promoters Bmp4 and Msx1 with and without MSX1 as co-activator. All mutant PAX9 proteins were localized in the nucleus of transfected cells and physically interacted with MSX1 protein. Three of the mutants retained the ability to bind the consensus paired domain recognition sequence; the others were unable or only partly able to interact with this DNA fragment and also showed a similarly impaired capability for activation of transcription from the Msx1 and Bmp4 promoters. For seven of the eight mutants, the degree of loss of DNA-binding and promoter activation correlated quite well with the severity of the tooth agenesis pattern seen in vivo. One of the mutants however showed neither reduction in DNA-binding nor decrease in transactivation; instead, a loss of responsiveness to synergism with MSX1 in target promoter activation and a dominant negative effect when expressed together with wild-type PAX9 could be observed. Our structure-based studies, which modeled DNA binding and subdomain stability, were able to predict functional consequences quite reliably.

Counterclockwise Craniofacial Distraction Osteogenesis.

Anatomic studies have identified that patients with Treacher Collins syndrome and some cases of bilateral craniofacial microsomia are characterized by multilevel airway obstruction as a result of hypoplasia and clockwise rotation of the maxillomandibular complex. Patients often remain tracheostomy-dependent despite multiple airway surgeries. Counterclockwise craniofacial distraction osteogenesis aims to correct the facial skeletal deformity and expand the upper airway volume by rotating the subcranial complex en bloc around the nasofrontal junction. Early results have demonstrated significant increases in the nasopharyngeal and oropharyngeal airway volumes with successful decannulation in a majority of patients who have undergone this operation.

A Comparative Assessment of Nasal Appearance following Nasoalveolar Molding and Primary Surgical Repair for Treatment of Unilateral Cleft Lip and Palate.

BACKGROUND: Although many cleft teams have adopted nasoalveolar molding to improve nasal form, few comparative studies have assessed the postoperative benefits of this treatment. Given that reported outcomes have been contradictory and that treatment involves considerable burden to families, the purpose of this study was to assess objective and subjective changes from nasoalveolar molding at approximately 5 years of age. METHODS: All patients with complete unilateral cleft lip and palate who underwent primary cheiloplasty performed by a single surgeon over a 7-year period were reviewed. Patient results were grouped into nasoalveolar molding or no-nasoalveolar molding. Cleft severity and aesthetic outcomes were assessed by panels of raters who independently ranked subject images at presentation, immediately preoperative (after molding), and at 5-year follow-up. Objective symmetry was measured using standard anthropometric analysis on three-dimensional images. RESULTS: Among 41 patients included, 16 successfully completed nasoalveolar molding. Both groups were similar at presentation; however, the nasoalveolar molding group had improved appearance following molding (p < 0.05). After surgery, at 5 years of age, the nasoalveolar molding group had better rank scores for overall appearance (p < 0.05), cleft nostril height, and cleft medial lip height (p < 0.05). Regression analysis revealed that nasoalveolar molding treatment was the most significant predictor of overall nasal appearance at 5 years, but that treatment team experience and initial severity were also significant predictors (p < 0.05). Qualitative audit following analysis identified favorable and unfavorable features of nasoalveolar molding. CONCLUSION: In children with complete unilateral cleft lip and palate, nasoalveolar molding was associated with better overall nasal aesthetics and improved cleft nostril height and cleft medial lip height at approximately 5 years of age. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Lefort II distraction with zygomatic repositioning versus Lefort III distraction: A comparison of surgical outcomes and complications.

The aim of the study was to determine if the additional surgical complexity of Lefort II distraction with zygomatic repositioning (LF2ZR) results in increased complications compared to Lefort III distraction (LF3). A retrospective review was performed of all LF3 and LF2ZR advancements performed by the senior author over 15 years. Demographic, operative, postoperative, and cephalometric data were collected from initial procedure through greater than 1 year postoperatively. Univariate and multivariate analyses were performed to compare procedures. 19 LF2ZR and 39 LF3 in 53 patients met inclusion criteria. Diagnoses differed between procedures, with more Crouzon Syndrome in LF3 and more Apert Syndrome in LF2ZR. Complication rate was 7/19 for LF2ZR and 12/39 for LF3 with no severe morbidity or mortality, and no difference between procedures (p = 0.56). The types of complications encountered differed between procedures. LF2ZR had a significantly longer operative time (506 ± 18 vs. 358 ± 24 min, p<0.001). However, a greater number of LF2ZR patients underwent concomitant procedures (15/19 vs. 13/39, p<0.001). Multivariate analysis revealed that Apert Syndrome and reoperative midface advancement were the most significant predictors of increased blood loss. LF2ZR has an equivalent complication rate to LF3. Therefore, it is our treatment of choice for cases requiring differential sagittal and vertical distraction of the central midface.

LeFort Distraction in the Cleft Patient.

The cleft patient may present with significant maxillary deficiency requiring maxillary advancement to establish balanced facial form and function. Often these skeletal advancements require movement of the maxilla of more than 10 mm. The cleft patient poses special challenges because of difficulty of mobilizing tissues on a multiply operated maxilla, as well as long-term stability. Distraction osteogenesis is a technique that may be applied to help move the maxilla over a long distance and slowly expand the soft tissues. A discussion of the orthodontic and surgical considerations when planning and executing the technique is presented.

Surgical-Orthodontic Considerations in Subcranial and Frontofacial Distraction.

Subcranial and frontofacial distraction osteogenesis have emerged as powerful tools for management of hypoplasia involving the upper two-thirds of the face. The primary goal of subcranial or frontofacial distraction is to improve the orientation of the upper face and midface structures (frontal bone, orbitozygomatic complex, maxilla, nasal complex) relative to the cranial base, globes, and mandible. The various techniques used are tailored for management of specific phenotypic differences in facial position and may include segmental osteotomies, differential vectors, or synchronous maxillomandibular rotation.

Nasoalveolar Molding for Unilateral and Bilateral Cleft Lip Repair.

Nasoalveolar molding (NAM) is a powerful tool in the treatment of patients with unilateral or bilateral cleft lip and palate. The primary goal of NAM is to improve alignment of critical anatomic elements before surgical repair of the unilateral or bilateral cleft lip. Modifications of the position of the alveolar segments and their associated lip elements, the lower lateral cartilages, and the columella achieved with NAM are helpful for creating a suitable platform for tension-free lip repair.

Identification and functional analysis of two novel PAX9 mutations.

The paired-domain transcription factor PAX9 plays a critical role in tooth development, as heterozygous mutations in PAX9 have been shown to be associated with human tooth agenesis. In this study, we report 2 novel missense mutations, gly6arg (G6R) and ser43lys (S43K), in the paired domain of PAX9 in Chinese patients with varying degrees of nonsyndromic tooth agenesis. Excluding third molars, the individual with the G6R mutation was missing 2 mandibular incisors and a maxillary premolar, while the phenotype of individuals with the S43K mutation consisted of peg-shaped upper lateral incisors and missing molars, premolars and canines. As these 2 mutations occur at highly conserved amino acids in the PAX gene family and between different species, we further analyzed the effects of the mutations on the function of the resulting proteins. Immunofluorescence and immunoblotting studies showed that the mutations did not alter nuclear localization in mammalian cells. Gel shift and super shift assays indicate that both mutant proteins bound DNA at a lower level than the normal protein, with G6R having a greater affinity for DNA than S43K. Likewise, the G6R protein was able to transcriptionally activate a Bmp4 promoter construct to a greater extent than S43K. Our finding that the severity of tooth agenesis in the patients was correlated to the DNA-binding capacity of the mutated PAX9 9proteins supports the hypothesis that DNA binding is responsible for the genetic defect.

Genetics and human malformations.

Genetics gains more and more importance in all areas of health care including craniofacial surgery and dentistry. This does not mean that every patient will benefit from genetic advances, but for many health problems, we will see progress in explaining disease pathogenesis, establishing diagnosis, guiding therapy, predicting prognosis, and achieving prevention. In this report, we briefly review the roles of the PAX9, MSX1, AXIN2, and EDA genes in the causation of congenital tooth agenesis and the promise of molecular genetic research for the improvement of patient care.

Counterclockwise Craniofacial Distraction Osteogenesis for Tracheostomy-Dependent Children with Treacher Collins Syndrome.

BACKGROUND: The craniofacial rotation deformity in Treacher Collins syndrome results in airway compression that is not addressed by isolated mandibular distraction osteogenesis. Our purpose is to present a surgical technique-counterclockwise craniofacial distraction osteogenesis-that improves airway morphology and occlusal rotation in tracheostomy-dependent patients with this condition. METHODS: All patients underwent subcranial Le Fort II osteotomies with simultaneous mandibular osteotomies, followed by coordinated maxillomandibular distraction with counterclockwise rotation. We reviewed pretreatment, posttreatment, and end-treatment cephalograms. Airway changes were assessed using polysomnography, sleep endoscopy, and direct laryngoscopy. Bivariate statistics were computed to compare pretreatment and posttreatment measures. RESULTS: Five subjects (age range, 4.5 to 12.1 years) underwent this new procedure; three had previously undergone mandibular distraction. The average palatal plane rotation was 17 degrees, the effective mandible length increase was 18 mm, and the facial plane relative to skull base rotation was 14 degrees. There was a symmetric 30 percent relapse of rotation with maintained occlusion in the first 9 months of follow-up that then stabilized. Four patients were successfully decannulated following counterclockwise craniofacial distraction osteogenesis following polysomnography. Sleep endoscopy available on two patients demonstrated resolution of the upper airway obstruction. CONCLUSIONS: Counterclockwise craniofacial distraction osteogenesis provided greater palatal rotation than previous techniques. The resulting improvement in airway anatomy allowed for decannulation in four of five tracheotomized patients. Stability of the counterclockwise rotation is comparable to that of related orthognathic operations, despite substantially greater magnitude. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.