The Cleft Palate–Craniofacial Journal 52(5) pp. 506–511 September 2015 Ó Copyright 2015 American Cleft Palate–Craniofacial Association
ORIGINAL ARTICLE Change in Mandibular Position in Patients With Syndromic Craniosynostosis After Midfacial Advancement With Distraction Osteogenesis Naeem Ali, B.S., Katherine Brustowicz, B.A., Naoshi Hosomura, D.D.S., Richard A. Bruun, D.D.S., Bonnie L. Padwa, D.M.D., M.D. Objective: Characterize mandibular morphology in patients with syndromic craniosynostosis and document changes in mandibular position following midfacial advancement using distraction osteogenesis (DO). Design: Retrospective chart review and analysis of cephalometric radiographs. Setting: Tertiary care center. Patients: Patients with syndromic craniosynostosis who had midfacial advancement with DO at Boston Children’s Hospital between 2000 and 2012. Mandibular morphology was characterized in 26 patients (15 boys and 11 girls) with a mean age of 11 years, 9 months. Pre- and postoperative analyses were performed for 17 (10 boys and 7 girls) of the 26 patients with a mean age of 11 years, 9 months. Main Outcome Measures: Mandibular morphology and mandibular position. Data were compared to standard data from the Michigan Growth Study. Results: Comparison of preoperative mandibular measurements to standard data showed that patients with syndromic craniosynostosis have a shorter mandibular body and length and an obtuse gonial angle. Comparison of pre- and postoperative cephalograms showed that, following midfacial advancement with DO, the maxilla moved forward and the mandible moved backward and downward. Conclusions: Patients with syndromic craniosynostosis have a smaller mandible length and obtuse gonial angle. Correction of midfacial hypoplasia with DO results in inferior and posterior mandibular movement. Clinicians can use this information to counsel patients regarding anticipated changes in facial profile and the need for adjunct procedures. KEY WORDS:
craniosynostosis, distraction osteogenesis, Le Fort osteotomy
Genetic mutations in the fibroblast growth factor
Muenke, 1999; Melville et al., 2010). Patients with syndromic craniosynostosis have midfacial hypoplasia that predisposes them to exorbitism, respiratory distress, and obstructive sleep apnea (Shetye et al., 2007; Nelson et al., 2008). LeFort III midfacial advancement increases orbital volume, improves midfacial position, and opens the airway space (Kaban et al., 1984; Ousterhout and Vargervik, 1987; Nelson et al., 2008; Shetye et al., 2010). A posterior and inferior (clockwise) change in the position of the mandible has been observed following LeFort III midfacial advancement (Bu et al., 1989; Shetye et al., 2010). LeFort III midfacial advancement using distraction osteogenesis (DO) provides greater advancement compared to a single-stage osteotomy (Fearon, 2001). The larger midfacial advancement obtained with DO has the potential to increase the magnitude and change the direction of mandibular movement. The objective of this study was to characterize the mandibular morphology in patients with syndromic craniosynostosis and document the effects of midfacial DO on the mandibular position.
(FGF) receptor family of genes are responsible for most forms of syndromic craniosynostosis (Hehr and
Mr. Ali is student, Harvard School of Dental Medicine, Boston, Massachusetts. Ms. Brustowicz is Research Assistant, Boston Children’s Hospital, Boston, Massachusetts. Dr. Hosomura is Resident, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts. Dr. Bruun is Assistant Clinical Professor, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Boston Children’s Hospital, Boston, Massachusetts. Dr. Padwa is Associate Professor, Harvard School of Dental Medicine, Boston, Massachusetts; Boston Children’s Hospital, Boston, Massachusetts. Previously presented at the 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies, Orlando, Florida, May 6, 2013. This project was supported by funds from the Scholars in Medicine Office, Harvard Medical School, and by the Department of Oral and Maxillofacial Surgery Education and Research Fund, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital. Submitted May 2014; Accepted July 2014. Address correspondence to: Dr. Bonnie L. Padwa, Department of Plastic and Oral Surgery, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. E-mail bonnie.padwa@childrens. harvard.edu DOI: 10.1597/14-157 506
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
MATERIALS
AND
507
METHODS
Subjects This was a retrospective review of patients with syndromic craniosynostosis who underwent Le Fort III midfacial advancement with DO at Boston Children’s Hospital between 2000 and 2012. Institutional review board approval was obtained from the Committee on Clinical Investigation at Boston Children’s Hospital. Patients with syndromic craniosynostosis who had midfacial advancement using the technique of DO and who had pre- and postoperative cephalograms taken within a 2-year period were included in this study. Control data for comparison to the study group were gathered from historic age- and sex-matched cephalometric measurements from the Michigan Growth Study (MGS) (Riolo et al., 1974). Cephalometric Analysis Pre- and postoperative lateral cephalometric radiographs were digitized with Dolphin Imaging System software (Dolphin Imaging, Canoga Park, CA). Twenty-three cephalometric landmarks were identified on the lateral cephalograms (Fig. 1). Each pre- and postoperative lateral cephalogram was traced twice, 1 week apart, by one author (N.A.) to assess intrarater reliability. To determine tracing accuracy, the tracings of a random subset of five patients were compared to those of a second author (N.H.). Differences in mandibular morphology, size, and position in syndromic patients were demonstrated by comparing the following preoperative mandibular measurements to control data from the MGS: ramus height (Ar-Go, Co-Go), body length (Go-Me, Go-Pg), ratio of ramus height to body length (Co-Go/Go-Me), mandibular length (Co-Pg, Ar-Gn), gonial angle (Ar-Go-Me), and mandibular protrusion/retrusion angle (S-N-B, SN-Pg). An ethmoid registration point to the pterygomaxillary fissure line (PTM) was used instead of a true vertical line in this study so that the patient’s natural head position could be standardized for making measurements. Preand postoperative midfacial and mandibular linear and angular measurements were obtained to evaluate the effects of midfacial distraction on the position of the mandible. Vertical changes in the maxilla were assessed using anterior facial height (N-Me), posterior facial height (S-Go), anterior to posterior facial height ratio (N-Me/S-Go), upper facial height (N-ANS), sellanasion line to palatal plane angle (S-N to ANS-PNS), and ethmoid registration point (SE) to PTM line to palatal plane angle (SE-PTM and ANS-PNS). Vertical mandibular changes were determined using sella-nasion line to mandibular plane angle (S-N to Go-Me), y-axis
FIGURE 1 Cephalometric landmarks used for measurements. Sella (S), ethmoid registration point (SE), nasion (N), condylion (Co), articulare (Ar), pterygomaxillary fissure inferior (PTM), basion (Ba), anterior nasal spine (ANS), posterior nasal spine (PNS), A-point (A), incisal tip of the maxillary central incisor (U1), maxillary first molar mesial cusp tip (U6), incisal tip of the mandibular central incisor (L1), mandibular first molar mesial cusp tip (L6), B-point (B), (Pg), gnathion (Gn), menton (Me), gonion (Go), most superior point of the odontoid process (OD), midpoint between OD and C2I (C2M), most anterior and inferior point on the C2 vertebra (C2I), and most anterior and superior point on the C3 vertebra (C3S).
angle (S-N to S-Gn), and SE-PTM line to mandibular plane angle (SE-PTM to Go-Me). Sagittal maxillary changes were evaluated using basion to A-point (Ba-A), perpendicular line from SE-PTM line to A-point (SEPTM perp A), maxillary protrusion/retrusion angle (SN-A). Mandibular sagittal changes were assessed using basion to B-point (Ba-B), perpendicular line from SEPTM line to B-point (SE-PTM perp B), mandibular protrusion/retrusion angle (S-N-B). Maxillomandibular comparisons were made using maxillomandibular position angle (A-N-B), palatal plane to mandibular plane angle (ANS-PNS to Go-Me), and facial profile (N-APg). In addition, dental measurements of overbite and overjet were also recorded. Pre- and postoperative maxillary and mandibular measurements were each compared to MGS data to determine the differences versus the normal population before and after midfacial advancement. These comparisons were made using anterior facial height (N-Me), maxillary protrusion/retrusion angle (S-N-A), mandibular protrusion/retrusion angle (S-N-B), maxillomandibular position angle (A-N-B), facial profile (N-A-Pg), and mandibular plane angle (S-N to Go-Me), because
508
Cleft Palate–Craniofacial Journal, September 2015, Vol. 52 No. 5
TABLE 1 Values
Comparison of Preoperative and Normal Mandibular
Measurement
Preoperative
Normal
Mean Difference
Co-Go (mm) Ar-Go (mm) Go-Me (mm) Go-Pg (mm) Co-Go/Go-Me Co-Pg (mm) Ar-Gn (mm) Ar-Go-Me (8) S-N-Pg (8) S-N-B (8) Ar-Go-Gn (8)
55.88 48.46 48.08 50.79 1.18 92.99 94.37 133.75 79.88 80.71 130.55
54.87 44.79 70.55 75.68 0.78 113.56 108.99 127.08 77.43 77.04 —
1.02 3.67* 22.47* 24.89* 0.40* 20.57* 14.62* 6.68* 2.45 3.67* —
* Statistically significant difference (P , .05).
all these maxillary and mandibular measurements were included in the MGS data for comparison. Statistics Data were analyzed using SPSS version 19.0 (IBM SPSS Inc., Chicago, IL). A paired t test analyzed the significant differences between preoperative and MGS variables, as well as between pre- and postoperative variables. Intraexaminer reliability and accuracy in cephalometric tracing were calculated using intraclass correlation coefficients. RESULTS Twenty-six patients (15 boys and 11 girls) with syndromic craniosynostosis (Apert ¼ 9, Pfeiffer ¼ 9, Crouzon ¼ 7, Muenke ¼ 1) had LeFort III midfacial advancement with either a rigid external distraction device (KLS Martin LP, Jacksonville, FL), a semiburied distraction device (Synthes, Paoli, PA), or a combination of the two at a mean age of 11 years and 9 months. Distraction commenced between 1 and 3 days postoperatively, at a rate of 1 mm per day, for an average of 20.79 days (range, 6 to 34 days). Patients were returned to the operating room for removal of the device an average of 6.47 weeks (range, 1 to 12 weeks) after completion of distraction. Comparison of preoperative mandibular measurements to standard MGS data showed that patients with syndromic craniosynostosis had a statistically significantly different mandibular shape than that of the normal population (Table 1). Patients with syndromic craniosynostosis had a shorter body length (Go-Me, Go-Pg), larger ramus height to body length ratio (Co-Go/Go-Me), smaller mandibular length (Co-Pg, Ar-Gn), and an obtuse gonial angle (Ar-Go-Me) compared to age- and sex-matched norms. The measurements for ramus height (Ar-Go and Co-Go) provided contradictory results. The measurement Ar-Go was larger in syndromic patients, indicating a longer ramus height compared to the normal population, while the measure Co-Go showed no difference in ramus height.
TABLE 2
Changes Following Distraction Osteogenesis
Postoperative
Mean Change
33.96 70.61 32.55 67.57 2.87 66.56
43.59 84.25 45.22 82.16 8.92 74.16
9.64* 13.64* 12.67* 14.59* 6.05* 7.60*
Mandible N-Me (mm) S-N-B (8) SE-PTM Perp B (mm) Ba-B (mm) S-N to Go-Me (8) S-N to S-Gn (8) SE-PTM to Go-Me (8)
100.82 82.90 53.56 85.56 34.64 67.48 98.96
109.14 78.84 50.47 89.50 39.84 71.32 105.32
8.32* 4.06* 3.09* 3.94* 5.19* 3.84* 6.36*
Maxillomandibular S-Go (mm) N-Me/S-Go A-N-B (8) ANS-PNS to Go-Me (8) N-A-Pg (8)
71.81 1.41 12.28 31.78 19.19
73.86 1.49 5.41 30.90 11.24
2.05 0.07* 17.69* 0.88 30.43*
7.29 4.90
4.09 5.21
11.39* 0.31
Measurement Midface N-ANS (mm) S-N-A (8) SE-PTM Perp A (mm) Ba-A (mm) S-N to ANS-PNS (8) SE-PTM and ANS-PNS (8)
Dental Overjet (mm) Overbite (mm)
Preoperative
* Statistically significant difference (P , .05).
Contradictory results were also found for mandibular protrusion/retrusion angle; S-N-B was larger in syndromic patients, suggesting a protruded mandible, while S-N-Pg was not different from the norm. Only 17 (10 boys and 7 girls) of the 26 patients (mean age, 11 years, 9 months) had both pre- and postoperative cephalograms taken within a 2-year period available for analysis. Preoperative cephalograms were taken a mean of 3.35 months (range, 0.20 to 11.55 months) prior to and postoperative cephalograms were taken a mean of 5.49 months (range, 0.20 to 17.30 months) after the operation. The patients in this study showed considerable improvement at the level of the midface following DO (Table 2). There was statistically significant (P , .05) sagittal advancement at the level of SE-PTM perpendicular to Apoint line. Distraction led to an overall forward (S-N-A) and inferior movement (N-ANS) of the maxilla. A significant increase was observed in the ratio of anterior to posterior facial height. Following distraction, the mandible moved in a clockwise direction, as seen by a decrease in the mandibular protrusion/retrusion angle (SN-B) and an increase in the mandibular plane angle (S-N to Go-Me). There was a statistically significant increase in the amount of dental overjet following advancement of the midface. Statistically significant differences in the maxillary and mandibular positions were found for syndromic patients when compared to norms (Table 3). Prior to midfacial advancement, syndromic patients had a shorter facial height (N-Me), greater maxillary retrusion (S-N-A), more
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
TABLE 3
Comparison of Preoperative and Normal Measurements
Measurement N-Me (mm) S-N-A (8) S-N-B (8) A-N-B (8) N-A-Pg (8) S-N to Go-Me (8)
Preoperative 100.82 70.61 82.90 12.28 19.19 34.64
Normal 120.37 81.17 77.14 4.04 7.28 34.28
TABLE 4 Comparison of Postoperative and Normal Measurements
Mean Difference 19.55* 10.56* 5.76* 16.32* 26.47* 0.36
* Statistically significant difference (P , .05).
509
Measurement
Postoperative
Normal
Mean Change
N-Me (mm) S-N-A (8) S-N-B (8) A-N-B (8) N-A-Pg (8) S-N to Go-Me (8)
109.14 84.25 78.84 5.41 11.24 39.84
122.29 81.05 77.27 3.81 6.49 34.01
13.15* 3.19 1.57 1.60 4.75 5.83
* Statistically significant difference (P , .05).
mandibular protrusion (S-N-B), and a concave facial profile (N-A-Pg). Following midfacial advancement, the study population still exhibited shorter facial height but was found to have no statistically significant differences in maxillary sagittal position, mandibular sagittal position, maxillomandibular relationship, mandibular plane angle, or facial profile when compared to the normal population (Table 4). Tests of intrarater reliability and cephalometric tracings found no significant differences for any of the measurements.
DISCUSSION This retrospective study demonstrated that patients with syndromic craniosynostosis have a distinct mandibular shape/morphology compared to normal patients. The ratio of ramus height to mandibular body length shows a larger ramus height than body length (Fig. 2), which is the opposite of what is found in the normal population. In addition, the angle formed by the ramus and mandibular body is more obtuse, causing the chin to be positioned more inferiorly compared to norms. A comparison of ramus height between the syndromic group and the normal
FIGURE 2 Preoperative mandibular cephalometric tracings illustrated no significant difference in ramus height (Co-Go) but a shorter body length (GoMe), a shorter mandibular length (Co-Pg), a more obtuse gonial angle (Ar-Go-Me), and a protruded mandible (S-N-B) compared to normal values obtained from the MGS data.
510
Cleft Palate–Craniofacial Journal, September 2015, Vol. 52 No. 5
population yielded inconclusive results, since the measurements for Co-Go and Ar-Go contradicted each other. The reliability of Ar-Go to measure ramus height in syndromic patients has been questioned previously, as these patients possess cranial base aberrations that alter the position of Ar (Costaras-Volarich and Pruzansky, 1984). The measure Co-Go demonstrated no difference in ramus height between syndromic patients and the normal population. Contradictory results for mandibular protrusion/retrusion angle were also found in our analysis. The inconsistency between S-N-B and S-N-Pg can be understood by considering the unique mandibular morphology and shorter anterior cranial base of syndromic patients and the effect that these factors have on the S-N-B and S-N-Pg angles. The larger gonial angle found in syndromic patients alters the relative horizontal positions of the landmarks Bpoint and Pg. While the horizontal position of B-point is posterior to Pg in normal individuals, the increased gonial angle found in the mandibles of syndromic patients results in B-point being positioned anterior to Pg. This explains the contradictory results for S-N-B and S-N-Pg. The shorter cranial base found in syndromic patients (Grayson et al., 1985), which increases the angle between S-N and N-B/NPg, leads to relative mandibular protrusion. The value for S-N-B is consistent with the mandibular protrusion observed in syndromic patients and thus should be considered before the findings for S-N-Pg. Our findings are consistent with the limited evidence that exists regarding the mandibular morphology of patients with syndromic craniosynostosis. Bu et al. (1989) found a larger mean gonial angle and larger ratio of ramus height to body length in patients with Apert or Crouzon syndrome. Costaras-Volarich and Pruzansky (1984) showed that the ramus height was equal to or longer, and that both body and mandibular length were shorter, in patients with Apert or Crouzon syndrome versus normal subjects. Le Fort III midfacial advancement with DO causes the mandible to move in a clockwise direction (Fig. 3). Postoperatively, patients have a longer anterior facial height, a more anteriorly and inferiorly positioned maxilla, and a more posteriorly and inferiorly placed mandible. These changes result in a hyperdivergent facial pattern and a change from the presurgical concave profile to one that is convex (Fig. 4). To our knowledge, this is the first study to detail the facial profile changes that occur at the level of the mandible in patients with syndromic craniosynostosis who had Le Fort III midfacial advancement with DO. As a result of the larger midfacial advancement that is attainable with DO (Shetye et al., 2010), we expected a greater clockwise movement of the mandible compared to single-stage advancement. However, a comparison of the magnitude of change at the level of the mandible after midfacial advancement could not be made, as previous studies describing single-stage advancement either included limited linear and angular measurements or used nonstandard
FIGURE 3 Preoperative (black) and postoperative (gray) cephalometric mandible tracings of a patient with syndromic craniosynostosis illustrating the clockwise (posterior and inferior) movement of the mandible that occurred with midfacial advancement after DO was performed.
cephalometric measurements. Bu et al. (1989) reported inferior movement of the mandible in patients with Apert or Crouzon syndrome following single-stage advancement. Shetye et al. (2010) used changes in the x- and y-coordinates of identified cephalometric landmarks to describe inferior and posterior movement of the mandible in syndromic patients following midfacial advancement. Although these studies (Bu et al., 1989; Shetye et al., 2010) reported limited information or used nonstandard cephalometric measurements, they described an overall clockwise directional movement of the mandible, which is consistent with our findings. The effectiveness of LeFort III midfacial advancement with DO in altering the facial profiles of syndromic patients so that they resemble those of the normal population was assessed by comparing pre- and postoperative measurements to normative data. Preoperative analysis revealed a shorter facial height, a more retruded maxilla, mandibular protrusion, and a concave facial profile compared to the normal population. Postoperative comparison to the normative data showed a shorter facial height but no statistically significant differences in maxillary position, mandibular position, and facial profile. It was previously reported (Bu et al., 1989) that syndromic patients have a steep mandibular plane compared to the norms. However, preoperative comparisons of our patients to normative data found no statistically significant difference in mandibular plane angle. Reitsma et al. (2013) evaluated pre- and postoperative horizontal and vertical cephalometric changes in the sagittal plane in
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
511
FIGURE 4 Pre- and postoperative lateral photographs of a patient with Crouzon syndrome. Note that with midfacial advancement the maxilla has moved anteriorly and inferiorly and the mandible has moved posteriorly and inferiorly, resulting in a longer anterior facial height and convex facial profile.
patients with Apert or Crouzon syndrome who underwent LeFort III midfacial advancement with DO. Preoperative comparisons of syndromic patients to norms demonstrated maxillary retrusion but no statistically significant difference in the mandibular position. This is slightly different from our study, which documented that, in addition to maxillary retrusion, syndromic patients also have mandibular protrusion in comparison to normal measurements. In the study by Reitsma et al. (2013), postoperative evaluation of syndromic patients showed no significant differences in maxillary and mandibular position when compared to norms, which is consistent with our findings. The inclusion of all FGF mutations, rather than only Apert and Crouzon patients, as was done in previous studies, along with the use of normative data exclusively from the MGS, may explain the differences in our findings. CONCLUSION Syndromic craniosynostosis is a relatively rare condition, which fundamentally introduces limitations to this study. Given the small cohort available to us, we were unable to determine whether there were dissimilarities among the different FGF mutations (syndromes). Nonetheless, our study provides new information about the mandibular characteristics of patients with FGF mutations. This study also details the impact of Le Fort III midfacial advancement with DO on the position of the mandible, which has not previously been reported. This information can aid clinicians in counseling patients and their families about the facial profile changes that will occur as a result of midfacial advancement and the potential need for other procedures to correct profile changes at the level of the mandible.
REFERENCES Bu BH, Kaban LB, Vargervik K. Effect of Le Fort III osteotomy on mandibular growth in patients with Crouzon and Apert syndromes. J Oral Maxillofac Surg. 1989;47:666–671. Costaras-Volarich M, Pruzansky S. Is the mandible intrinsically different in Apert and Crouzon syndromes? Am J Orthod. 1984;85:475–487. Fearon JA. The Le Fort III osteotomy: to distract or not to distract? Plast Reconstr Surg. 2001;107:1091–1103. Grayson BH, Weintraub N, Bookstein FL, McCarthy JG. A comparative cephalometric study of the cranial base in craniofacial anomalies: part I: tensor analysis. C1eft Palate J. 1985;22:75–87. Hehr U, Muenke M. Craniosynostosis syndromes: from genes to premature fusion of skull bones. Mol Genet Metab. 1999;68:139–151. Kaban LB, West B, Conover M, Will L, Mulliken JB, Murray JE. Midface position after LeFort III advancement. Plast Reconstr Surg. 1984;73:758–767. Melville H, Wang Y, Taub PJ, Jabs EW. Genetic basis of potential therapeutic strategies for craniosynostosis. Am J Med Genet A. 2010;152A:3007–3015. Nelson TE, Mulliken JB, Padwa BL. Effect of midfacial distraction on the obstructed airway in patients with syndromic bilateral coronal synostosis. J Oral Maxillofac Surg. 2008;66:2318–2321. Ousterhout DK, Vargervik K. Aesthetic improvement resulting from craniofacial surgery in craniosynostosis syndromes. J Craniomaxillofac Surg. 1987;15:189–197. Reitsma JH, Ongkosuwito EM, Buschang PH, Adrichem LN, PrahlAndersen B. Craniofacial stability in patients with the syndrome of Crouzon and Apert after Le Fort III distraction osteogenesis. Cleft Palate Craniofac J. 2013;50:561–569. Riolo ML, Moyers RE, McNamara JA, Hunter WS. An Atlas of Craniofacial Growth. 7th ed. Monograph 2, Craniofacial Growth Series. Ann Arbor: Center for Human Growth and Development, University of Michigan; 1974. Shetye PR, Boutros S, Grayson BH, McCarthy JG. Midterm followup of midface distraction for syndromic craniosynostosis: a clinical and cephalometric study. Plast Reconstr Surg. 2007;120:1621–1632. Shetye PR, Kapadia H, Grayson BH, McCarthy JG. A 10-year study of skeletal stability and growth of the midface following Le Fort III advancement in syndromic craniosynostosis. Plast Reconstr Surg. 2010;126:973–981.
ORIGINAL ARTICLE Change in Mandibular Position in Patients With Syndromic Craniosynostosis After Midfacial Advancement With Distraction Osteogenesis Naeem Ali, B.S., Katherine Brustowicz, B.A., Naoshi Hosomura, D.D.S., Richard A. Bruun, D.D.S., Bonnie L. Padwa, D.M.D., M.D. Objective: Characterize mandibular morphology in patients with syndromic craniosynostosis and document changes in mandibular position following midfacial advancement using distraction osteogenesis (DO). Design: Retrospective chart review and analysis of cephalometric radiographs. Setting: Tertiary care center. Patients: Patients with syndromic craniosynostosis who had midfacial advancement with DO at Boston Children’s Hospital between 2000 and 2012. Mandibular morphology was characterized in 26 patients (15 boys and 11 girls) with a mean age of 11 years, 9 months. Pre- and postoperative analyses were performed for 17 (10 boys and 7 girls) of the 26 patients with a mean age of 11 years, 9 months. Main Outcome Measures: Mandibular morphology and mandibular position. Data were compared to standard data from the Michigan Growth Study. Results: Comparison of preoperative mandibular measurements to standard data showed that patients with syndromic craniosynostosis have a shorter mandibular body and length and an obtuse gonial angle. Comparison of pre- and postoperative cephalograms showed that, following midfacial advancement with DO, the maxilla moved forward and the mandible moved backward and downward. Conclusions: Patients with syndromic craniosynostosis have a smaller mandible length and obtuse gonial angle. Correction of midfacial hypoplasia with DO results in inferior and posterior mandibular movement. Clinicians can use this information to counsel patients regarding anticipated changes in facial profile and the need for adjunct procedures. KEY WORDS:
craniosynostosis, distraction osteogenesis, Le Fort osteotomy
Genetic mutations in the fibroblast growth factor
Muenke, 1999; Melville et al., 2010). Patients with syndromic craniosynostosis have midfacial hypoplasia that predisposes them to exorbitism, respiratory distress, and obstructive sleep apnea (Shetye et al., 2007; Nelson et al., 2008). LeFort III midfacial advancement increases orbital volume, improves midfacial position, and opens the airway space (Kaban et al., 1984; Ousterhout and Vargervik, 1987; Nelson et al., 2008; Shetye et al., 2010). A posterior and inferior (clockwise) change in the position of the mandible has been observed following LeFort III midfacial advancement (Bu et al., 1989; Shetye et al., 2010). LeFort III midfacial advancement using distraction osteogenesis (DO) provides greater advancement compared to a single-stage osteotomy (Fearon, 2001). The larger midfacial advancement obtained with DO has the potential to increase the magnitude and change the direction of mandibular movement. The objective of this study was to characterize the mandibular morphology in patients with syndromic craniosynostosis and document the effects of midfacial DO on the mandibular position.
(FGF) receptor family of genes are responsible for most forms of syndromic craniosynostosis (Hehr and
Mr. Ali is student, Harvard School of Dental Medicine, Boston, Massachusetts. Ms. Brustowicz is Research Assistant, Boston Children’s Hospital, Boston, Massachusetts. Dr. Hosomura is Resident, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts. Dr. Bruun is Assistant Clinical Professor, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Boston Children’s Hospital, Boston, Massachusetts. Dr. Padwa is Associate Professor, Harvard School of Dental Medicine, Boston, Massachusetts; Boston Children’s Hospital, Boston, Massachusetts. Previously presented at the 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies, Orlando, Florida, May 6, 2013. This project was supported by funds from the Scholars in Medicine Office, Harvard Medical School, and by the Department of Oral and Maxillofacial Surgery Education and Research Fund, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital. Submitted May 2014; Accepted July 2014. Address correspondence to: Dr. Bonnie L. Padwa, Department of Plastic and Oral Surgery, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115. E-mail bonnie.padwa@childrens. harvard.edu DOI: 10.1597/14-157 506
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
MATERIALS
AND
507
METHODS
Subjects This was a retrospective review of patients with syndromic craniosynostosis who underwent Le Fort III midfacial advancement with DO at Boston Children’s Hospital between 2000 and 2012. Institutional review board approval was obtained from the Committee on Clinical Investigation at Boston Children’s Hospital. Patients with syndromic craniosynostosis who had midfacial advancement using the technique of DO and who had pre- and postoperative cephalograms taken within a 2-year period were included in this study. Control data for comparison to the study group were gathered from historic age- and sex-matched cephalometric measurements from the Michigan Growth Study (MGS) (Riolo et al., 1974). Cephalometric Analysis Pre- and postoperative lateral cephalometric radiographs were digitized with Dolphin Imaging System software (Dolphin Imaging, Canoga Park, CA). Twenty-three cephalometric landmarks were identified on the lateral cephalograms (Fig. 1). Each pre- and postoperative lateral cephalogram was traced twice, 1 week apart, by one author (N.A.) to assess intrarater reliability. To determine tracing accuracy, the tracings of a random subset of five patients were compared to those of a second author (N.H.). Differences in mandibular morphology, size, and position in syndromic patients were demonstrated by comparing the following preoperative mandibular measurements to control data from the MGS: ramus height (Ar-Go, Co-Go), body length (Go-Me, Go-Pg), ratio of ramus height to body length (Co-Go/Go-Me), mandibular length (Co-Pg, Ar-Gn), gonial angle (Ar-Go-Me), and mandibular protrusion/retrusion angle (S-N-B, SN-Pg). An ethmoid registration point to the pterygomaxillary fissure line (PTM) was used instead of a true vertical line in this study so that the patient’s natural head position could be standardized for making measurements. Preand postoperative midfacial and mandibular linear and angular measurements were obtained to evaluate the effects of midfacial distraction on the position of the mandible. Vertical changes in the maxilla were assessed using anterior facial height (N-Me), posterior facial height (S-Go), anterior to posterior facial height ratio (N-Me/S-Go), upper facial height (N-ANS), sellanasion line to palatal plane angle (S-N to ANS-PNS), and ethmoid registration point (SE) to PTM line to palatal plane angle (SE-PTM and ANS-PNS). Vertical mandibular changes were determined using sella-nasion line to mandibular plane angle (S-N to Go-Me), y-axis
FIGURE 1 Cephalometric landmarks used for measurements. Sella (S), ethmoid registration point (SE), nasion (N), condylion (Co), articulare (Ar), pterygomaxillary fissure inferior (PTM), basion (Ba), anterior nasal spine (ANS), posterior nasal spine (PNS), A-point (A), incisal tip of the maxillary central incisor (U1), maxillary first molar mesial cusp tip (U6), incisal tip of the mandibular central incisor (L1), mandibular first molar mesial cusp tip (L6), B-point (B), (Pg), gnathion (Gn), menton (Me), gonion (Go), most superior point of the odontoid process (OD), midpoint between OD and C2I (C2M), most anterior and inferior point on the C2 vertebra (C2I), and most anterior and superior point on the C3 vertebra (C3S).
angle (S-N to S-Gn), and SE-PTM line to mandibular plane angle (SE-PTM to Go-Me). Sagittal maxillary changes were evaluated using basion to A-point (Ba-A), perpendicular line from SE-PTM line to A-point (SEPTM perp A), maxillary protrusion/retrusion angle (SN-A). Mandibular sagittal changes were assessed using basion to B-point (Ba-B), perpendicular line from SEPTM line to B-point (SE-PTM perp B), mandibular protrusion/retrusion angle (S-N-B). Maxillomandibular comparisons were made using maxillomandibular position angle (A-N-B), palatal plane to mandibular plane angle (ANS-PNS to Go-Me), and facial profile (N-APg). In addition, dental measurements of overbite and overjet were also recorded. Pre- and postoperative maxillary and mandibular measurements were each compared to MGS data to determine the differences versus the normal population before and after midfacial advancement. These comparisons were made using anterior facial height (N-Me), maxillary protrusion/retrusion angle (S-N-A), mandibular protrusion/retrusion angle (S-N-B), maxillomandibular position angle (A-N-B), facial profile (N-A-Pg), and mandibular plane angle (S-N to Go-Me), because
508
Cleft Palate–Craniofacial Journal, September 2015, Vol. 52 No. 5
TABLE 1 Values
Comparison of Preoperative and Normal Mandibular
Measurement
Preoperative
Normal
Mean Difference
Co-Go (mm) Ar-Go (mm) Go-Me (mm) Go-Pg (mm) Co-Go/Go-Me Co-Pg (mm) Ar-Gn (mm) Ar-Go-Me (8) S-N-Pg (8) S-N-B (8) Ar-Go-Gn (8)
55.88 48.46 48.08 50.79 1.18 92.99 94.37 133.75 79.88 80.71 130.55
54.87 44.79 70.55 75.68 0.78 113.56 108.99 127.08 77.43 77.04 —
1.02 3.67* 22.47* 24.89* 0.40* 20.57* 14.62* 6.68* 2.45 3.67* —
* Statistically significant difference (P , .05).
all these maxillary and mandibular measurements were included in the MGS data for comparison. Statistics Data were analyzed using SPSS version 19.0 (IBM SPSS Inc., Chicago, IL). A paired t test analyzed the significant differences between preoperative and MGS variables, as well as between pre- and postoperative variables. Intraexaminer reliability and accuracy in cephalometric tracing were calculated using intraclass correlation coefficients. RESULTS Twenty-six patients (15 boys and 11 girls) with syndromic craniosynostosis (Apert ¼ 9, Pfeiffer ¼ 9, Crouzon ¼ 7, Muenke ¼ 1) had LeFort III midfacial advancement with either a rigid external distraction device (KLS Martin LP, Jacksonville, FL), a semiburied distraction device (Synthes, Paoli, PA), or a combination of the two at a mean age of 11 years and 9 months. Distraction commenced between 1 and 3 days postoperatively, at a rate of 1 mm per day, for an average of 20.79 days (range, 6 to 34 days). Patients were returned to the operating room for removal of the device an average of 6.47 weeks (range, 1 to 12 weeks) after completion of distraction. Comparison of preoperative mandibular measurements to standard MGS data showed that patients with syndromic craniosynostosis had a statistically significantly different mandibular shape than that of the normal population (Table 1). Patients with syndromic craniosynostosis had a shorter body length (Go-Me, Go-Pg), larger ramus height to body length ratio (Co-Go/Go-Me), smaller mandibular length (Co-Pg, Ar-Gn), and an obtuse gonial angle (Ar-Go-Me) compared to age- and sex-matched norms. The measurements for ramus height (Ar-Go and Co-Go) provided contradictory results. The measurement Ar-Go was larger in syndromic patients, indicating a longer ramus height compared to the normal population, while the measure Co-Go showed no difference in ramus height.
TABLE 2
Changes Following Distraction Osteogenesis
Postoperative
Mean Change
33.96 70.61 32.55 67.57 2.87 66.56
43.59 84.25 45.22 82.16 8.92 74.16
9.64* 13.64* 12.67* 14.59* 6.05* 7.60*
Mandible N-Me (mm) S-N-B (8) SE-PTM Perp B (mm) Ba-B (mm) S-N to Go-Me (8) S-N to S-Gn (8) SE-PTM to Go-Me (8)
100.82 82.90 53.56 85.56 34.64 67.48 98.96
109.14 78.84 50.47 89.50 39.84 71.32 105.32
8.32* 4.06* 3.09* 3.94* 5.19* 3.84* 6.36*
Maxillomandibular S-Go (mm) N-Me/S-Go A-N-B (8) ANS-PNS to Go-Me (8) N-A-Pg (8)
71.81 1.41 12.28 31.78 19.19
73.86 1.49 5.41 30.90 11.24
2.05 0.07* 17.69* 0.88 30.43*
7.29 4.90
4.09 5.21
11.39* 0.31
Measurement Midface N-ANS (mm) S-N-A (8) SE-PTM Perp A (mm) Ba-A (mm) S-N to ANS-PNS (8) SE-PTM and ANS-PNS (8)
Dental Overjet (mm) Overbite (mm)
Preoperative
* Statistically significant difference (P , .05).
Contradictory results were also found for mandibular protrusion/retrusion angle; S-N-B was larger in syndromic patients, suggesting a protruded mandible, while S-N-Pg was not different from the norm. Only 17 (10 boys and 7 girls) of the 26 patients (mean age, 11 years, 9 months) had both pre- and postoperative cephalograms taken within a 2-year period available for analysis. Preoperative cephalograms were taken a mean of 3.35 months (range, 0.20 to 11.55 months) prior to and postoperative cephalograms were taken a mean of 5.49 months (range, 0.20 to 17.30 months) after the operation. The patients in this study showed considerable improvement at the level of the midface following DO (Table 2). There was statistically significant (P , .05) sagittal advancement at the level of SE-PTM perpendicular to Apoint line. Distraction led to an overall forward (S-N-A) and inferior movement (N-ANS) of the maxilla. A significant increase was observed in the ratio of anterior to posterior facial height. Following distraction, the mandible moved in a clockwise direction, as seen by a decrease in the mandibular protrusion/retrusion angle (SN-B) and an increase in the mandibular plane angle (S-N to Go-Me). There was a statistically significant increase in the amount of dental overjet following advancement of the midface. Statistically significant differences in the maxillary and mandibular positions were found for syndromic patients when compared to norms (Table 3). Prior to midfacial advancement, syndromic patients had a shorter facial height (N-Me), greater maxillary retrusion (S-N-A), more
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
TABLE 3
Comparison of Preoperative and Normal Measurements
Measurement N-Me (mm) S-N-A (8) S-N-B (8) A-N-B (8) N-A-Pg (8) S-N to Go-Me (8)
Preoperative 100.82 70.61 82.90 12.28 19.19 34.64
Normal 120.37 81.17 77.14 4.04 7.28 34.28
TABLE 4 Comparison of Postoperative and Normal Measurements
Mean Difference 19.55* 10.56* 5.76* 16.32* 26.47* 0.36
* Statistically significant difference (P , .05).
509
Measurement
Postoperative
Normal
Mean Change
N-Me (mm) S-N-A (8) S-N-B (8) A-N-B (8) N-A-Pg (8) S-N to Go-Me (8)
109.14 84.25 78.84 5.41 11.24 39.84
122.29 81.05 77.27 3.81 6.49 34.01
13.15* 3.19 1.57 1.60 4.75 5.83
* Statistically significant difference (P , .05).
mandibular protrusion (S-N-B), and a concave facial profile (N-A-Pg). Following midfacial advancement, the study population still exhibited shorter facial height but was found to have no statistically significant differences in maxillary sagittal position, mandibular sagittal position, maxillomandibular relationship, mandibular plane angle, or facial profile when compared to the normal population (Table 4). Tests of intrarater reliability and cephalometric tracings found no significant differences for any of the measurements.
DISCUSSION This retrospective study demonstrated that patients with syndromic craniosynostosis have a distinct mandibular shape/morphology compared to normal patients. The ratio of ramus height to mandibular body length shows a larger ramus height than body length (Fig. 2), which is the opposite of what is found in the normal population. In addition, the angle formed by the ramus and mandibular body is more obtuse, causing the chin to be positioned more inferiorly compared to norms. A comparison of ramus height between the syndromic group and the normal
FIGURE 2 Preoperative mandibular cephalometric tracings illustrated no significant difference in ramus height (Co-Go) but a shorter body length (GoMe), a shorter mandibular length (Co-Pg), a more obtuse gonial angle (Ar-Go-Me), and a protruded mandible (S-N-B) compared to normal values obtained from the MGS data.
510
Cleft Palate–Craniofacial Journal, September 2015, Vol. 52 No. 5
population yielded inconclusive results, since the measurements for Co-Go and Ar-Go contradicted each other. The reliability of Ar-Go to measure ramus height in syndromic patients has been questioned previously, as these patients possess cranial base aberrations that alter the position of Ar (Costaras-Volarich and Pruzansky, 1984). The measure Co-Go demonstrated no difference in ramus height between syndromic patients and the normal population. Contradictory results for mandibular protrusion/retrusion angle were also found in our analysis. The inconsistency between S-N-B and S-N-Pg can be understood by considering the unique mandibular morphology and shorter anterior cranial base of syndromic patients and the effect that these factors have on the S-N-B and S-N-Pg angles. The larger gonial angle found in syndromic patients alters the relative horizontal positions of the landmarks Bpoint and Pg. While the horizontal position of B-point is posterior to Pg in normal individuals, the increased gonial angle found in the mandibles of syndromic patients results in B-point being positioned anterior to Pg. This explains the contradictory results for S-N-B and S-N-Pg. The shorter cranial base found in syndromic patients (Grayson et al., 1985), which increases the angle between S-N and N-B/NPg, leads to relative mandibular protrusion. The value for S-N-B is consistent with the mandibular protrusion observed in syndromic patients and thus should be considered before the findings for S-N-Pg. Our findings are consistent with the limited evidence that exists regarding the mandibular morphology of patients with syndromic craniosynostosis. Bu et al. (1989) found a larger mean gonial angle and larger ratio of ramus height to body length in patients with Apert or Crouzon syndrome. Costaras-Volarich and Pruzansky (1984) showed that the ramus height was equal to or longer, and that both body and mandibular length were shorter, in patients with Apert or Crouzon syndrome versus normal subjects. Le Fort III midfacial advancement with DO causes the mandible to move in a clockwise direction (Fig. 3). Postoperatively, patients have a longer anterior facial height, a more anteriorly and inferiorly positioned maxilla, and a more posteriorly and inferiorly placed mandible. These changes result in a hyperdivergent facial pattern and a change from the presurgical concave profile to one that is convex (Fig. 4). To our knowledge, this is the first study to detail the facial profile changes that occur at the level of the mandible in patients with syndromic craniosynostosis who had Le Fort III midfacial advancement with DO. As a result of the larger midfacial advancement that is attainable with DO (Shetye et al., 2010), we expected a greater clockwise movement of the mandible compared to single-stage advancement. However, a comparison of the magnitude of change at the level of the mandible after midfacial advancement could not be made, as previous studies describing single-stage advancement either included limited linear and angular measurements or used nonstandard
FIGURE 3 Preoperative (black) and postoperative (gray) cephalometric mandible tracings of a patient with syndromic craniosynostosis illustrating the clockwise (posterior and inferior) movement of the mandible that occurred with midfacial advancement after DO was performed.
cephalometric measurements. Bu et al. (1989) reported inferior movement of the mandible in patients with Apert or Crouzon syndrome following single-stage advancement. Shetye et al. (2010) used changes in the x- and y-coordinates of identified cephalometric landmarks to describe inferior and posterior movement of the mandible in syndromic patients following midfacial advancement. Although these studies (Bu et al., 1989; Shetye et al., 2010) reported limited information or used nonstandard cephalometric measurements, they described an overall clockwise directional movement of the mandible, which is consistent with our findings. The effectiveness of LeFort III midfacial advancement with DO in altering the facial profiles of syndromic patients so that they resemble those of the normal population was assessed by comparing pre- and postoperative measurements to normative data. Preoperative analysis revealed a shorter facial height, a more retruded maxilla, mandibular protrusion, and a concave facial profile compared to the normal population. Postoperative comparison to the normative data showed a shorter facial height but no statistically significant differences in maxillary position, mandibular position, and facial profile. It was previously reported (Bu et al., 1989) that syndromic patients have a steep mandibular plane compared to the norms. However, preoperative comparisons of our patients to normative data found no statistically significant difference in mandibular plane angle. Reitsma et al. (2013) evaluated pre- and postoperative horizontal and vertical cephalometric changes in the sagittal plane in
Ali et al., MANDIBULAR POSITION IN PATIENTS WITH SYNDROMIC CRANIOSYNOSTOSIS
511
FIGURE 4 Pre- and postoperative lateral photographs of a patient with Crouzon syndrome. Note that with midfacial advancement the maxilla has moved anteriorly and inferiorly and the mandible has moved posteriorly and inferiorly, resulting in a longer anterior facial height and convex facial profile.
patients with Apert or Crouzon syndrome who underwent LeFort III midfacial advancement with DO. Preoperative comparisons of syndromic patients to norms demonstrated maxillary retrusion but no statistically significant difference in the mandibular position. This is slightly different from our study, which documented that, in addition to maxillary retrusion, syndromic patients also have mandibular protrusion in comparison to normal measurements. In the study by Reitsma et al. (2013), postoperative evaluation of syndromic patients showed no significant differences in maxillary and mandibular position when compared to norms, which is consistent with our findings. The inclusion of all FGF mutations, rather than only Apert and Crouzon patients, as was done in previous studies, along with the use of normative data exclusively from the MGS, may explain the differences in our findings. CONCLUSION Syndromic craniosynostosis is a relatively rare condition, which fundamentally introduces limitations to this study. Given the small cohort available to us, we were unable to determine whether there were dissimilarities among the different FGF mutations (syndromes). Nonetheless, our study provides new information about the mandibular characteristics of patients with FGF mutations. This study also details the impact of Le Fort III midfacial advancement with DO on the position of the mandible, which has not previously been reported. This information can aid clinicians in counseling patients and their families about the facial profile changes that will occur as a result of midfacial advancement and the potential need for other procedures to correct profile changes at the level of the mandible.
REFERENCES Bu BH, Kaban LB, Vargervik K. Effect of Le Fort III osteotomy on mandibular growth in patients with Crouzon and Apert syndromes. J Oral Maxillofac Surg. 1989;47:666–671. Costaras-Volarich M, Pruzansky S. Is the mandible intrinsically different in Apert and Crouzon syndromes? Am J Orthod. 1984;85:475–487. Fearon JA. The Le Fort III osteotomy: to distract or not to distract? Plast Reconstr Surg. 2001;107:1091–1103. Grayson BH, Weintraub N, Bookstein FL, McCarthy JG. A comparative cephalometric study of the cranial base in craniofacial anomalies: part I: tensor analysis. C1eft Palate J. 1985;22:75–87. Hehr U, Muenke M. Craniosynostosis syndromes: from genes to premature fusion of skull bones. Mol Genet Metab. 1999;68:139–151. Kaban LB, West B, Conover M, Will L, Mulliken JB, Murray JE. Midface position after LeFort III advancement. Plast Reconstr Surg. 1984;73:758–767. Melville H, Wang Y, Taub PJ, Jabs EW. Genetic basis of potential therapeutic strategies for craniosynostosis. Am J Med Genet A. 2010;152A:3007–3015. Nelson TE, Mulliken JB, Padwa BL. Effect of midfacial distraction on the obstructed airway in patients with syndromic bilateral coronal synostosis. J Oral Maxillofac Surg. 2008;66:2318–2321. Ousterhout DK, Vargervik K. Aesthetic improvement resulting from craniofacial surgery in craniosynostosis syndromes. J Craniomaxillofac Surg. 1987;15:189–197. Reitsma JH, Ongkosuwito EM, Buschang PH, Adrichem LN, PrahlAndersen B. Craniofacial stability in patients with the syndrome of Crouzon and Apert after Le Fort III distraction osteogenesis. Cleft Palate Craniofac J. 2013;50:561–569. Riolo ML, Moyers RE, McNamara JA, Hunter WS. An Atlas of Craniofacial Growth. 7th ed. Monograph 2, Craniofacial Growth Series. Ann Arbor: Center for Human Growth and Development, University of Michigan; 1974. Shetye PR, Boutros S, Grayson BH, McCarthy JG. Midterm followup of midface distraction for syndromic craniosynostosis: a clinical and cephalometric study. Plast Reconstr Surg. 2007;120:1621–1632. Shetye PR, Kapadia H, Grayson BH, McCarthy JG. A 10-year study of skeletal stability and growth of the midface following Le Fort III advancement in syndromic craniosynostosis. Plast Reconstr Surg. 2010;126:973–981.
