Craniofacial morphology and adolescent facial growth in Pierre Robin sequence

ORIGINAL ARTICLE

Craniofacial morphology and adolescent facial growth in Pierre Robin sequence Sunjay Suri,a R. Bruce Ross,b and Bryan D. Tompsonc Toronto, Ontario, Canada Introduction: The purpose of this research was to analyze craniofacial morphology and adolescent facial growth in subjects with Pierre Robin sequence (PRS). The research was conducted at the Center for Craniofacial Care and Research at The Hospital for Sick Children, Toronto, Ontario, Canada, and the Burlington Facial Growth Research Center, Faculty of Dentistry, University of Toronto. Methods: Longitudinal lateral cephalometric tracings of 34 Caucasian subjects with nonsyndromic PRS were compared with those of unaffected control subjects, matched for age, sex, and ethnicity, and representing the range of occlusions in an untreated population. Cephalometric measurements were obtained before orthodontic treatment (age, 11.8 years) and after orthodontic treatment but before any surgical treatment (age, 16.6 years). Betweengroup differences of craniofacial measurements were analyzed with paired t-tests, and longitudinal growth differences were analyzed with analysis of variance (ANOVA) adjusted for the growth interval. Results: Significant differences were noted, with the PRS group showing smaller cranial base length, shorter maxillary and mandibular lengths, increased palatal and mandibular plane inclinations, and more open mandibular flexure. Mandibular body length and height were smaller as were ramal length and width, anterior basal thickness, and chin thickness. The ramus-to-body ratio was greater. With growth, greater gains in anterior face and symphyseal height were seen, but the mandible showed less closure of its internal flexure. The maxilla and the mandible remained retrusive during adolescent growth, and the maxilla became more retrognathic. Mandibular morphologic differences persisted in spite of additionally adjusting for cranial base length in the analysis. Conclusions: Subjects with PRS had reduced cranial base and maxillary and mandibular lengths. Mandibular deficiency was most pronounced in the body. Due to bimaxillary retrognathism, the maxillomandibular dysplasia was not significant. A vertical growth pattern worsened the profile. There was no evidence of adolescent mandibular catch-up growth. (Am J Orthod Dentofacial Orthop 2010;137:763-74)

P

ierre Robin sequence (PRS) is a craniofacial anomaly characterized by the triad of mandibular micrognathia, cleft palate, and severe upper airway obstruction all occurring at birth.1,2 Named after the French stomatologist Pierre Robin,3,4 who in 1923 and 1934 described multiple severe problems associated with micrognathia in the neonatal period.5 PRS has a reported prevalence between 1 in 85006 and 1 in 20,000 births.7 PRS has been described to be causally heterogeneous and pathogenetically and phenotypically variable. Mandibular micrognathia in PRS can be malformational, when due to intrinsic hypoFrom the Discipline of Orthodontics, Faculty of Dentistry, University of Toronto, and The Hospital for Sick Children, Toronto, Ontario, Canada. a Assistant professor; staff orthodontist, Division of Orthodontics. b Professor; staff orthodontist, Division of Orthodontics. c Associate professor and head, Division of Orthodontics. The authors report no commercial, proprietary, or financial interest in the products or companies described in this article. Reprint requests to: Sunjay Suri, Discipline of Orthodontics, Faculty of Dentistry, University of Toronto, 124 Edward St, Rm 519B, Toronto, ON M5G 1G6, Canada; e-mail, [email protected]. Submitted, April 2008; revised and accepted, July 2008. 0889-5406/$36.00 Copyright Ó 2010 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2008.07.020

plasia, or deformational, when due to intrauterine constraint.8 Micrognathia and glossoptosis can cause severe airway obstruction with feeding difficulties in the neonate; these can be fatal. Depending on the severity of airway compromise, various interventions can be required in the early management of an infant born with PRS.9,10 The literature reports conservative approaches such as prone positioning4,11,12 to more aggressive management techniques with head braces or suspension caps,13 mandibular advancement and traction appliances,14,15 nasopharyngeal intubation,10,16-18 and surgical interventions such as tongue-lip adhesion (glossopexy),16,19-24 tracheostomy,9,25,26 and mandibular distraction osteogenesis.27-30 Contrary to the earlier popular view that mandibular micrognathia in PRS is an effect of intrauterine constriction and that growth would catch up to normal, recent research has not shown significant catch-up growth.31-36 The current view is that the mandible is small at birth and remains small throughout active facial growth,37,38 and catch-up growth is only partial,39 leaving patients with PRS retrognathic and significantly convex in adulthood.40,41 A detailed analysis of the mandibular morphology and its longitudinal growth 763

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Table I.

American Journal of Orthodontics and Dentofacial Orthopedics June 2010

Sample characteristics: age (y) PRS group (n 5 34)

T1 T2

Mean

SD

Range

Mean

SD

Range

11.7 16.6

0.7 1.2

10.2-13.0 14.3-18.2

11.9 16.7

0.8 1.4

10.0-13.0 14.0-20.0

Boys (n 5 13)

T1 T2

Control group (n 5 34)

Girls (n 5 21)

Boys (n 5 13)

Girls (n 5 21)

Mean

SD

Range

Mean

SD

Range

Mean

SD

Range

Mean

SD

Range

11.8 15.9

0.9 1.2

10.2-13.0 14.6-18.1

11.6 16.9

0.6 1.2

10.6-12.7 14.3-18.2

11.8 16.3

1.0 1.1

10.0-13.1 14.0-18.2

12.0 16.9

0.6 1.5

11.0-13.0 14.1-20.0

compared with a matched control group of subjects has not been reported in the literature. The aims of this study were to analyze the craniofacial features and mandibular morphology in patients with PRS compared with an age- and sex-matched sample of unaffected normal control subjects, and to evaluate longitudinal growth differences during adolescence. MATERIAL AND METHODS

The sample consisted of Caucasian children with nonsyndromic PRS treated at the Center for Craniofacial Care and Research, The Hospital for Sick Children, Toronto, for whom longitudinal cephalometric radiographs were available. Children with other craniofacial anomalies in addition to PRS and other syndromes, and those who were not Caucasian, were excluded from the study. A diagnosis of PRS had been made for the patients based on cleft palate at birth, mandibular micrognathia, and at least 1 episode of respiratory distress in the neonatal period. Because of causal, pathogenetic, and phenotypic differences, PRS and Robin complex of various types can occur.8 PRS is also known to occur with other craniofacial syndromes. Because of the participation of experts from several disciplines in the craniofacial care of patients at the center, it was possible to select records of only subjects with PRS who did not have an associated syndrome. Due to the relatively low frequency of PRS, the sample included patients who had received treatment at the center at various times. All patients had received their palatal repair surgeries at the center. Surgical treatment had entailed palate repair between 15 and 24 months of age by any of the 4 surgeons who were a part of the team at the time of their surgeries. The most common surgical palate repair techniques included von Langenbeck and push-back palatoplasty. No secondary or revisionary palate surgical procedures were undertaken, and 1 patient had received a superiorly based pharyngeal flap. Two time points were selected for this study: T1, toward the end

of the transitional dentition period or just when the patient entered the permanent dentition stage of dental development, but before any orthodontic interventions; and T2, after completion of orthodontic treatment (but before orthognathic surgery if it was planned). These times were selected to approximate the prepubertal growth status and completion of active mandibular growth. No patient had received aggressive or surgical neonatal intervention. There were 34 children with PRS who fulfilled the inclusion criteria (the PRS group). For each child with PRS, an age- and sex-matched subject was selected from the normative cephalometric collection of Caucasian patients at the Burlington Facial Growth Research Center, Faculty of Dentistry, University of Toronto. To compare the craniofacial features in PRS with a control sample representing the unaffected population, it was determined to include the range of occlusions that would be found in an untreated population. Therefore, the control sample comprised 34 unaffected normal children who had received no orthodontic treatment. We selected 24 age- and sex-matched control subjects with Class I occlusion, 8 with Class II occlusion, and 2 with Class III occlusion (the control group). Normative cephalometric data were collected from films available at the ages most closely approximating those at T1 and T2 of the PRS group. Details of the PRS and control groups are presented in Table I. All cephalograms used in this study had been taken with a standardized technique and apparatus. The cephalograms were traced, and 103 landmarks were digitized for each cephalogram by 1 technician using Dentofacial Planner cephalometric software (Dentofacial Software, Toronto, Ontario, Canada). The cephalometric analysis used was a composite of measurements from conventional analyses, with additional landmarks and measurements defined to study the mandibular morphology in detail (Figs 1 and 2). An internal, geometrically constructed point, ramus body syncline (RBS), was defined as the point of intersection of the midplaned cortical outline of the

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American Journal of Orthodontics and Dentofacial Orthopedics Volume 137, Number 6

Fig 1. Mandibular landmarks. Conventional landmarks: Co, condylion; Go, gonion; Me, menton; Gn, gnathion; Pg, pogonion; B, supramentale; Id, infradentale; and Idl, lingual point infradentale. New landmarks used in this study: PAP, posterior alveolar point, most posteroinferior midplaned point on the anterior border of the ascending ramus; Inf Go, inferior gonion, midplaned point on the lower border of the mandible where the convexity at Go merges with the concavity of the antegonial notch; RBS, ramus body syncline, point of intersection of a line drawn from Inf Go to PAP with the cortical outline of the midplaned mandibular nerve; Bl, lingual point B, point of intersection of a line drawn from RBS to B, with the lingual contour of the symphysis; saj, symphysis-alveolar junction, midpoint of a line drawn from Bl to B; Pgl, lingual point pogonion, highest point on the lingual contour of the symphysis, as located by the greatest perpendicular distance from a line drawn from saj to Me; malv, midpoint of anterior alveolus, midpoint of line drawn from Idl to Id.

mandibular nerve with a line drawn from the most posteroinferior midplaned point on the anterior border of the ascending ramus (posterior alveolar point, PAP) to a midplaned point on the lower border of the mandible where the convexity at gonion merges with the concavity of the antegonial notch (inferior gonion, Inf Go) (Fig 1). RBS differentiates the internal ramal and body components of the mandible. A central axis of the symphysis, which measured the symphyseal height, was drawn from the midpoint of the basilar portion of the anterior mandible (the symphysis alveolar junction, saj), to menton (Me), whereas the axis from saj to the midpoint of the anterior alveolus (malv) measured the anterior alveolar height. RBS in conjunction with PAP, saj, malv, Inf Go, and Me allowed measurements of internal ramal length, internal body length, posterior and anterior mandibular alveolar heights, posterior mandibular body height, and symphyseal height and angular measurements such as internal mandibular

765

Fig 2. Mandibular measurements: mandibular length, Co-Gn; external ramal length, Co-Go; internal ramal length, Co-RBS; external body length, Go-Gn; internal body length, RBS-Gn; gonial angle, Co-Go-Gn; internal mandibular deflection, Co-RBS-Gn; posterior alveolar height, length of the perpendicular from PAP to RBSB; posterior body height, length of the perpendicular from Inf Go to RBS-B; anterior alveolar height, length of the line drawn from malv to saj; symphyseal height, length of the line drawn from the saj to Me; symphyseal thickness, sum of the lengths of perpendiculars from Pg and Pgl to a line drawn from saj to Me; mandibular deflection, internal angle between Go-Gn and the line drawn from saj to Me; ramal width, length of the line drawn from the midplaned deepest points on the posterior and anterior borders of the ramus; anterior basal width, length of the line drawn from Bl to B.

deflection and mandibular /symphyseal deflection. With the Dentofacial Planner software, the average tracings of the PRS group were superimposed on those of the control group at T1 (Figs 3 and 4) and T2 (Figs 5 and 6). To assess intraexaminer repeatability, radiographs of 13 randomly selected subjects from each group (26 subjects) were retraced and redigitized. Repeatability was assessed through linear and angular measurements recorded during both the observations, correlated by the intraclass correlation coefficient. The highly significant agreement of measurements recorded from the repeated tracings demonstrated excellent repeatability of the cephalometric method (Table II). Statistical analysis

The cephalometric data recorded were analyzed by using paired t tests to evaluate the differences at the 2 times with the Statistical Package for Social Sciences software (version 15, SPSS, Chicago, Ill), and the differences of growth increments in linear and angular measurements from T1 to T2 for each group were analyzed with analysis of variance (ANOVA) adjusted for the duration from T1 to T2 with Minitab 14

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Fig 4. Mandibular superimposition at T1 (RBS-Gn at symphysis); 1 represents the location of RBS. Fig 3. Cephalometric superimposition at T1 (sellanasion at sella); 1 represents the location of RBS.

statistical software (Minitab, State College, Pa). The mandibular measurements were further analyzed with 2-way ANOVA at each time point, adjusted for age, sex, and the measurement of the cranial base (represented by Ba-N) to eliminate any bias created by differences in basic stature or overall craniofacial size causing overrepresentation of the mandibular measurement differences. RESULTS

The descriptive measurements (unadjusted) for both the PRS and the control groups and the paired t-tests at both times are summarized in Table III, and the results of the analysis for growth from T1 to T2 with the ANOVA adjusted for the duration of growth interval are provided in Table IV. Results of the ANOVA for mandibular measurements at T1 and T2, adjusted for age, sex, and cranial base length are summarized in Table V. All cranial base linear measurements were smaller in the PRS group at both times (Table III). The cranial base angle was not different. Maxillary plane angulation to S-N was larger in the PRS group at both times, with no significant difference of growth changes between the 2 groups. The angular relationship of the mandible with the cranial base, represented by S-N/Go-Gn and Ba-N/ Co-Gn showed increased angulations in the PRS group. The change in angular relationships of the maxilla and mandible with respect to the cranial base during growth from T1 to T2 showed no significant differences in the

groups, except for the Ba-N/Co-Gn value, which in the control group had a small relative but significant reduction. The relative difference in reduction in the mandibular plane angle was borderline significant (Table IV). The differences in measurements of anterior face height, and upper and lower anterior face heights were not significant, although a reversal of the trend was noticed at T2, with the PRS group appearing (but not significantly) larger. There were significant differences in the increments in the anterior facial measurements, with the PRS group showing relatively larger gains for N-Me, N-ANS and ANS-Me. The posterior face height measurements were markedly smaller in the PRS group at both times, whereas the difference in increments from T1 to T2 was small and not significant. The effect of these was seen in the marked reductions in the Jarabak ratio (S-Go:N-Me) in the PRS group; the differences at T1 and T2 were highly significant. The linear measurements of the midface region showed a markedly smaller maxillary length in the PRS group at both times; however, the increment differences from T1 to T2 between the 2 groups were small and not significant. Similarly, the effective midfacial length (Co-A) was also much smaller in the PRS group at both times, and the differences were highly significant. The growth increments were, however, not different. Both SNA and SNB values were greatly reduced by about 5 to 6 each at both times, and the differences were highly significant, highlighting the severe bimaxillary retrognathism in the PRS group. However, the incremental difference from T1 to T2 was significant only for SNA, which showed a small increase in the controls but a small reduction in the PRS group (between-group

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767

Fig 6. Mandibular superimposition at T2 (RBS-Gn at symphysis); 1 represents the location of RBS.

Fig 5. Cephalometric superimposition at T2 (sellanasion at sella); 1 represents the location of RBS.

increment difference, 0.94 ; P \0.001). The relative protrusion of the maxilla and mandible (measured by A-N perpendicular and Pg-N perpendicular, respectively) showed greater maxillary and mandibular protrusion in the controls at T1 and T2. The improvement in relative protrusion from T1 to T2 was also significantly less in the PRS group than in the control group (maxillary intergroup difference, 1.48 mm, P \0.001; mandibular intergroup difference, 2.15 mm, P 5 0.003), with the PRS group showing further relative maxillary retrusion in the growth period (Table IV). The Wits appraisal was greater at T1 in the PRS group, and the difference was significant; it was not statistically significant at T2, and the growth change was not significantly different between the groups. The ANB difference was 1.17 at T1 but reduced to 0.79 at T2 and was not significant at either time. Differences in the maxillomandibular differential measurement were not significant at T1 or T2. The mandibular regional analysis showed shorter mandibular lengths (Co-Gn) in the PRS group by 8.33 mm (P \0.001) at T1 and 7.01 mm (P \0.001) at T2 (Table III) but no significant difference in the relative increments in mandibular length from T1 to T2 (Table IV). Mandibular body measurements had large and highly significant differences for both internal and external measurements at both times but no significant differences in their almost identical relative growth increments. The analysis of the ramal region showed

highly significant deficiencies in internal ramal length (Co-RBS) and external ramal length (Co-Go) in the PRS group at both times, but the growth increment differences were small and insignificant. The internal ramus to body ratio (RBS-Gn/Co-RBS X 100) had 7.03% relatively greater ramal component in the PRS group at T1 and 7.26% at T2, whereas the external ratio (Go-Gn/Co-Go X 100) showed greater ramal to body components of 5.42% at T1 and 6.91% at T2 in the PRS group. The adolescent incremental change in these ratios had no significant differential changes in the 2 groups. Ramal width was distinctly greater in the control group, but the growth increment was not different. The internal mandibular deflection and gonial angle, which describe the flexure of the mandible internally and externally, showed larger angles at T1 and T2, although a significant difference in the change with growth was noted only for internal mandibular deflection, which had relatively less longitudinal reduction in the PRS group (by 1.48 , P 5 0.03). The posterior mandibular alveolar height was similar in both groups at both times, but anterior alveolar height was greater in the PRS group. The posterior body height, on the other hand, was significantly larger in the controls at T1 and remained significantly larger at T2, although the growth increment differences for none of these measurements were significant between the groups. The anterior mandibular basal width was also greater in the control group; the difference was significant at T1 but increased to become highly significant at T2. The growth decrement in anterior basal width was also larger in the PRS group. The differences in sagittal symphyseal height were not significant at either time, but

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Table II.

American Journal of Orthodontics and Dentofacial Orthopedics June 2010

Intraexaminer repeatability of cephalometric measurements of 26 randomly selected subjects First tracing

Second tracing

Measurement

Mean

SD

Mean

SD

Intraexaminer measurement error*

S-N (mm) Ba-S (mm) Ba-N (mm) Cranial base angle (S-N/Ba-S) ( ) S-N/maxillary plane ( ) S-N/Go-Gn ( ) Ba-N/Co-Gn ( ) N-Me (mm) N-ANS (mm) ANS-Me (mm) S-Go (mm) Maxillary length (mm) Co-A (mm) Co-Gn (mm) SNA ( ) SNB ( ) ANB ( ) Wits appraisal (mm) Co-Go (mm) Go-Gn (mm) Internal ramal length (mm) Internal body length (mm) Ramal width (mm) Posterior mandibular alveolar height (mm) Posterior mandibular body height (mm) Anterior mandibular alveolar height (mm) Anterior mandibular basal width (mm) Sagittal symphyseal height (mm) Symphyseal thickness (mm) Internal mandibular deflection ( ) Gonial angle ( ) Mandibular/symphysis deflection ( )

70.68 45.36 105.30 129.30 9.89 35.34 77.00 114.17 52.19 66.92 71.85 51.07 87.44 110.14 79.64 75.30 4.35 3.58 52.53 70.33 57.32 55.54 32.75 14.13 10.42 9.95 9.38 21.33 14.40 155.72 130.22 68.30

3.49 2.91 5.05 5.41 3.91 7.30 5.43 7.14 3.49 6.00 5.54 4.76 5.78 6.61 3.76 4.10 3.06 3.90 3.94 6.34 3.62 4.79 3.23 2.07 1.64 2.39 1.57 2.64 1.91 5.84 6.86 6.34

70.72 45.31 105.35 129.42 9.99 35.48 77.23 113.96 52.22 66.94 71.91 51.29 87.32 110.25 79.57 75.29 4.28 3.64 52.78 70.31 57.48 55.52 32.57 14.20 10.36 9.91 9.27 21.23 14.36 155.52 129.88 68.40

3.45 2.87 4.99 5.51 3.89 7.23 5.30 7.37 3.47 6.17 5.52 4.74 5.63 6.57 3.79 4.13 3.10 3.85 3.95 6.16 3.54 4.75 3.09 2.02 1.67 2.30 1.58 2.72 1.87 5.89 6.85 6.43

0.03 0.02 0.03 0.03 0.03 0.03 0.04 0.08 0.02 0.04 0.03 0.04 0.03 0.04 0.02 0.02 0.02 0.04 0.05 0.05 0.04 0.04 0.04 0.03 0.03 0.04 0.02 0.05 0.04 0.07 0.07 0.09

Intraexaminer ICCC

P value

0.995 0.998 0.998 0.998 0.997 0.999 0.997 0.993 0.998 0.998 0.998 0.998 0.998 0.998 0.998 0.999 0.998 0.994 0.993 0.996 0.995 0.997 0.991 0.987 0.984 0.987 0.991 0.982 0.988 0.994 0.996 0.989

\0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001

*Method error 5 O S D2/2N, where D is the difference in the repeated measurements, and N is the number of double measurements.

a significant difference was noted in the growth increment, since the PRS group gained relatively more symphyseal height from T1 to T2 than did the controls. Chin thickness, on the other hand, was greater in the controls at both times but without a significant difference in the amount of incremental growth between the groups from T1 to T2. With growth from T1 to T2, the chin became more upright to the mandibular base in the PRS group (by 4.38 , P 5 0.003), and the differential change in this angle between the groups from T1 to T2 was also significant (P 5 0.04). The results of the 2-way ANOVA adjusted for age, sex, and Ba-N length on the mandibular measurements at T1 and T2 (Table V) largely agreed with the findings of the paired t-test and showed that the differences in mandibular length, external and internal body length, ramal width, and posterior mandibular body height at both times were highly significant, whereas differences in external ramal length were significant at T1 but not at T2, and significant differences

in anterior alveolar height increased in severity and became highly significant at T2. Differences in basal width were not significant at T1 but became highly significant at T2. In this adjusted analysis, internal ramal length, posterior mandibular alveolar height, symphyseal height, and chin thickness were not significantly different at T1 or T2. DISCUSSION

In this study, we aimed to provide a detailed longitudinal analysis of craniofacial morphology and adolescent facial growth in a reasonably large sample of subjects with PRS compared with matched unaffected controls. Such an analysis is lacking in the reported literature, even though this entity has been widely recognized since the last century. A unique feature of this study was that, to conduct the comparative analysis, the control sample was selected from race-, age-, and sex-matched unaffected subjects who had the same

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American Journal of Orthodontics and Dentofacial Orthopedics Volume 137, Number 6

Table III.

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Comparison of skeletal measurements of PRS group vs control group at T1 and T2 Comparison at T1 PRS group (n 5 34)

Comparison at T2

Control group (n 5 34)

Measurement

Mean

SD

Mean

SD

S-N (mm) Ba-S (mm) Ba-N (mm) Cranial base angle (S-N/Ba-S) ( ) S-N/Go-Gn ( ) Ba-N/Co-Gn ( ) S-N/maxillary plane ( ) N-Me (mm) N-ANS (mm) ANS-Me (mm) S-Go (mm) S-Go:N-Me (%) Maxillary length (mm) Co-A (mm) Co-Gn (mm) Maxillomandibular differential (mm) SNA ( ) SNB ( ) ANB ( ) Wits appraisal (mm) A-N perpendicular (mm) Pg-N perpendicular (mm) Internal ramal length (mm) Internal body length (mm) Co-Go (mm) Go-Gn (mm) Ramus/body ratio (internal) Ramus/body ratio (external) Ramal width (mm) Posterior mandibular alveolar height (mm) Posterior mandibular body height (mm) Anterior mandibular alveolar height (mm) Anterior mandibular basal width (mm) Sagittal symphyseal height (mm) Symphyseal thickness (mm) Internal mandibular deflection ( ) Gonial angle ( ) Mandibular/symphysis deflection ( )

69.51 44.00 103.42 130.17

2.91 72.31 3.46 46.64 4.32 108.23 4.52 129.94

2.97 2.35 4.09 4.99

39.94 79.39 12.83 112.07 51.80 66.13 68.24 59.11 48.04 83.64 105.78 22.13

6.76 30.99 4.22 73.31 3.86 8.94 7.98 114.22 3.33 52.81 6.56 65.47 6.04 73.84 4.59 63.47 4.04 54.66 5.06 90.59 6.23 114.11 4.69 23.52

76.53 72.16 4.39 3.53 6.48 18.73 55.36

3.75 3.92 2.97 3.54 4.42 7.88 3.91

52.09 50.36 65.22 106.63

Difference

Paired t-test

(control – PRS) P value

PRS group

Control group

(n 5 34)

(n 5 34)

t-test

SD

2.8 2.64 4.81 0.23

\0.01† 72.33 3.35 75.12 \0.01† 46.87 3.98 49.07 \0.001‡ 108.35 4.92 112.69 0.83 129.79 4.78 129.36

3.32 3.09 5.13 5.34

2.79 2.20 4.34 0.43

\0.01† \0.01† \0.01† 0.71

4.20 3.21 3.44 5.17 2.80 4.11 4.70 3.63 3.17 3.67 4.81 3.67

8.95 6.08 3.89 2.15 1.01 0.66 5.60 4.36 6.62 6.95 8.33 1.39

\0.001‡ 38.88 7.08 28.96 \0.001‡ 80.08 4.7 73.06 \0.001‡ 12.77 3.72 9.02 0.16 122.07 8.70 121.09 0.22 55.94 3.68 55.67 0.58 71.98 7.79 69.44 \0.001‡ 76.3 6.70 80.9 \0.001‡ 60.78 4.84 69.49 \0.001‡ 50.77 4.63 57.99 \0.001‡ 88.21 5.41 95.31 \0.001‡ 116.16 6.53 123.17 0.13 27.96 5.58 27.87

4.61 3.48 3.60 7.79 3.22 5.50 7.29 4.40 3.02 4.81 6.87 4.41

9.92 7.02 3.75 0.98 0.27 2.54 4.60 8.71 7.22 7.10 7.01 0.09

\0.001‡ \0.001‡ \0.001‡ 0.59 0.75 0.09 \0.01† \0.001‡ \0.001‡ \0.001‡ \0.001‡ 0.96

81.28 78.06 3.22 1.96 1.77 8.03 58.59

3.09 2.72 1.78 1.60 3.20 5.04 2.98

4.75 5.90 1.17 1.57 4.71 10.70 3.23

\0.001‡ \0.001‡ 0.06 \0.05* \0.001‡ \0.001‡ \0.001‡

82.07 79.55 2.51 2.40 1.01 4.73 64.45

3.20 2.75 1.94 1.74 3.53 5.25 4.20

5.69 6.47 0.79 1.53 6.20 12.85 2.79

\0.001‡ \0.001‡ 0.28 0.06 \0.001‡ \0.001‡ \0.01†

3.84 4.66 4.33 8.37

58.97 53.92 75.00 99.6

3.49 3.45 3.54 6.31

6.88 3.56 9.78 7.03

\0.001‡ 56.69 \0.001‡ 57.13 \0.001‡ 70.82 \0.01† 109.29

4.45 63.29 4.87 59.89 4.99 80.99 9.74 102.03

4.27 5.23 5.29 6.33

6.60 2.76 10.17 7.26

\0.001‡ \0.01† \0.001‡ \0.01†

77.37 7.03

71.95

4.16

5.42

\0.001‡

80.94 7.67

74.03

5.64

6.91

\0.001‡

30.8 2.19 14.19 2.18

34.39 13.83

2.30 2.51

3.59 0.36

\0.001‡ 0.54

31.37 2.48 14.6 2.60

35.24 13.68

2.97 2.50

3.87 0.92

\0.001‡ 0.14

9.56 1.67

11.59

1.86

2.03

\0.001‡

11.16 2.32

12.38

3.35

1.22

\0.05*

10.57 2.32

9.58

0.54

0.99

\0.05*

11.31 2.44

10.09

1.77

1.22

0.01*

8.90 1.56

9.66

1.31

0.76

\0.05*

7.69 1.48

9.15

1.56

1.46

\0.001†

20.19 2.41

21.18

2.16

0.99

0.07

23.19 2.67

23.28

2.62

0.09

0.85

13.42 1.08

14.75

0.98

1.33

\0.01†

13.96 1.20

15.54

1.17

1.58

\0.01†

160.48 5.17 152.87

5.51

7.61

\0.001‡ 158.89 6.02 149.79

5.07

9.10

\0.001‡

136.08 7.18 125.93 65.89 6.59 68.35

4.41 6.29

10.15 2.46

\0.001‡ 133.81 8.17 123.16 0.63 63.79 6.49 68.17

5.05 5.97

10.65 4.38

\0.001‡ \0.01†

76.38 73.08 3.30 3.93 7.21 17.58 61.66

SD

Difference

Mean

*P \0.05, significant; †P \0.01, highly significant; ‡P \0.001, very highly significant.

Mean

Paired

4.1 3.90 3.36 4.16 4.42 8.91 4.07

(control – PRS) P value

770

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Table IV.

American Journal of Orthodontics and Dentofacial Orthopedics June 2010

Comparison of growth increments in linear and angular skeletal measurements between the groups from

T1 to T2 Control group (n 5 34)

PRS group(n 5 34)

ANOVA (adjusted for duration of growth interval from T1 to T2)

Measurement

Mean

SD

Mean

SD

P value

S-N (mm) Ba-S (mm) Ba-N (mm) Cranial base angle (S-N/Ba-S) ( ) S-N/Go-Gn ( ) Ba-N/Co-Gn ( ) S-N/maxillary plane ( ) N-Me (mm) N-ANS (mm) ANS-Me (mm) S-Go (mm) Maxillary length (mm) Co-A (mm) Co-Gn (mm) SNA ( ) SNB ( ) ANB ( ) Wits appraisal (mm) A-N perpendicular (mm) Pg-N perpendicular (mm) Internal ramal length (mm) Internal body length (mm) Co-Go (mm) Go-Gn (mm) Ramus/body ratio (internal) Ramus/body ratio (external) Ramal width (mm) Posterior mandibuloar alveolar height (mm) Posterior mandibular body height (mm) Anterior mandibular alveolar height (mm) Anterior mandibular basal width (mm) Sagittal symphyseal height (mm) Symphyseal thickness (mm) Internal mandibular deflection ( ) Gonial angle ( ) Mandibular/symphysis deflection ( )

2.82 2.87 4.93 0.38 1.07 0.69 0.05 10.00 4.14 5.85 8.05 2.73 4.57 10.38 0.15 0.92 1.09 0.40 0.72 1.15 6.30 4.60 6.77 5.60 2.65 3.58 0.57 0.41 1.6 0.74 1.21 2.99 0.53 1.59 2.27 2.09

1.38 2.05 2.46 1.14 2.43 1.94 1.53 4.90 2.31 2.51 4.07 1.88 2.61 4.23 1.18 1.51 1.29 2.41 1.39 3.44 2.65 2.73 4.14 2.57 6.18 7.07 1.68 1.62 1.62 2.08 1.04 1.68 0.78 3.38 2.64 4.09

2.81 2.43 4.45 0.58 2.03 0.25 0.08 6.87 2.86 3.97 7.06 3.32 4.72 9.07 0.79 1.50 0.71 0.44 0.76 3.30 5.86 4.33 5.96 5.99 2.43 2.08 0.84 0.15 0.79 0.51 0.51 2.10 0.80 3.07 2.76 0.18

1.82 2.06 3.08 0.97 1.77 1.42 0.87 5.49 1.91 2.82 3.90 2.16 2.88 4.82 1.01 1.30 1.03 1.41 1.13 2.72 3.11 3.01 3.20 3.59 5.41 2.88 1.92 1.22 1.81 1.32 0.87 1.54 0.70 2.43 2.10 3.06

0.93 0.41 0.52 0.39 0.05 \0.05* 0.69 \0.05* \0.05* \0.05* 0.33 1.20 0.73 0.24 \0.01† 0.05 0.20 0.93 \0.001‡ \0.01† 0.59 0.76 0.40 0.50 0.92 0.27 0.51 0.11 0.07 0.58 \0.01† \0.05* 0.13 \0.05* 0.33 \0.05*

*P \0.05, significant; †P \0.01, highly significant; ‡P \0.001, very highly significant.

occlusal features as would be found in a random sample of untreated subjects rather than a control group of predominantly Class I or Class II subjects. A cleft palate was a pathognomonic, characteristic feature required for the diagnosis of PRS in the sample included. Our aim was to study the craniofacial features in PRS, including the cumulative effects of various procedures required to treat the condition that might have affected the craniofacial form and growth of this anomaly. We did not adjust for the confounding effect of the surgical procedures or other factors related to treatment that could have affected craniofacial growth. Therefore our control sample did not include subjects with a repaired

isolated cleft palate, unlike other studies that had a group with repaired cleft palate as controls.38-44 The cephalometric method used in this study, previously reported by Suri et al,45 offers a great advantage in allowing the analysis of the regional detail. The use of internal landmarks does not restrict the analysis of mandibular morphology solely to external measurements from landmarks that could be affected by remodeling changes around muscle attachments on the surface. This allowed us to study the mandibular structures and regional details more comprehensively. The longitudinal cephalometric analysis showed that the PRS group had smaller cranial bases and larger

American Journal of Orthodontics and Dentofacial Orthopedics Volume 137, Number 6

Results of 2-way ANOVA of linear mandibular skeletal measurements of the PRS group vs the control group adjusted for age, sex, and Ba-N length

Table V.

Adjusted Adjusted ANOVA at T1 ANOVA at T2 Measurement Co-Gn Internal ramal length Internal body length Co-Go Go-Gn Ramal width Posterior mandibular alveolar height Posterior mandibular body height Anterior mandibular alveolar height Anterior mandibular basal width Symphyseal thickness Symphyseal height

P value

P value

\0.001‡ 0.07 \0.001‡ \0.05* \0.001‡ \0.001‡ 0.71 \0.001‡ \0.05* 0.21 0.18 0.56

\0.001‡ 0.07 \0.001‡ 0.09 \0.001‡ \0.001‡ 0.38 \0.05* \0.01† \0.01† 0.08 0.51

*P \0.05, significant; †P \0.01, highly significant; ‡P \0.001, very highly significant.

maxillary and mandibular plane angulations, and tended to have smaller posterior face height at both times. Although the PRS subjects had similar anterior face height measurements at the 2 times, they accrued relatively larger linear increments in anterior face measurements compared with their age-, sex-, and racial groupmatched controls. Bimaxillary retrognathism was clearly evident in the PRS group. The maxillary length was shorter by 12.3% in the PRS group, and the maxilla was more steeply inclined to the cranial base in a downward-backward rotation pattern. The mandible in the PRS group was small throughout the study period, and the pattern of diminished growth did not alter compared with the control group, showing an absence of significantly greater differential or catch-up growth during adolescence. It was not in the scope of this study to describe whether a partial catch-up of mandibular growth in the PRS group might have occurred during infancy. From the results of the various mandibular components, it was evident that the greatest deficiencies quantified in the mandible (mean of T1 and T2 values) were in the posterior mandibular body height (13.7%), body length (11.9%), and anterior mandibular basal width (11.9%), followed by ramal width (10.7%), chin thickness (9.6%), and ramal length (5.3%), leading to the 6.5% deficiency in total mandibular length. These clarify a significantly reduced mandibular bony volume in PRS, with the greatest deficits in the region of the mandibular body. The ramus-to-body ratio consistently showed a relatively shorter body (7.15% internal, 6.17% external) in the PRS group. The narrower chin, with the decreased relative closure of the mandibular flexure and

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mandibular plane angle in the PRS sample during adolescent growth, and greater relative gain in its own height, became more retroclined to the mandibular plane during the adolescent growth period. The mandibular plane to cranial base angle and internal mandibular flexure showed smaller differential reductions in the PRS group, and their growth rotation relatively was downward and backward. The sagittal projection of the maxilla and SNA showed further reduction in the PRS group, whereas they increased in the controls during the growth period. The mandible showed relatively less projection. However, due to the relatively severe bimaxillary retrognathism, the maxillomandibular relationships were not significantly worse when compared with the controls. The findings of bimaxillary deficiency and retrognathism and increased vertical pattern partially agree with those reported by Matsuda et al46 on a smaller compilation of case studies of 5 Japanese subjects with PRS compared with published Japanese norms. However, our larger series of 34 PRS subjects showed smaller cranial base length without a large ANB angle or differential growth increment in any linear mandibular measurement except greater gain in chin height and greater reduction of anterior basal width. Although ‘‘sequence’’ in the nomenclature PRS is used to describe that mandibular micrognathia is the primary pathogenetic event that causes the cleft palate and upper airway obstruction, it does not explain the highly significant reduction in the linear measurements of the cranial base, which is a prior craniomorphogenetic event than the growth of the mandible. We evaluated craniofacial form and growth during adolescence. Therefore, we cannot comment on whether a small mandible and resultant feeding difficulties might have caused poor growth and smaller overall stature, and indirectly contributed to reduced cranial base growth as a part of generalized craniofacial growth reduction because of failure to thrive in infancy. Some studies on PRS during infancy described reduced cranial size39 and cranial base length compared with unaffected subjects, unilateral cleft lip, and complete cleft lip and palate43,44; others found no significant differences in cranial base measurements compared with isolated cleft palate at age 5 years or later in adolescence.38 Interestingly, some recent reports described a neuroembryologic basis and brainstem dysgenesis in the prenatal and neonatal periods in the pathogenesis of PRS,47,48 and others have pointed out the possibility of greater genetic influence.49-52 In our study, the reduction in linear measurements in the PRS group was not uniform in the 3 major craniofacial regions. In general, measurements were smaller by about 4% for the cranial base, 12% for the maxilla, and 6.5% for the mandible.

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Fig 7. Cephalometric superimposition at T1 (basion-nasion), with PRS tracing adjusted to match length of Ba-N with the control group; 1 represents the location of RBS.

The short maxillary length is explained by the surgically repaired palatal cleft, and the deficiency in cranial base length and mandible volume are explained by deficient growth and the distinct mandibular morphologic features characteristic of PRS. It is possible that the children with PRS were generally smaller in stature than the controls. It could be argued that the faces in the PRS group were therefore generally smaller than those in the control group, with this effect shown by the reduced cranial base measurements. To test whether there were any significant residual differences in the mandibular measurements beyond this explanation, the mandibular measurements were further analyzed with 2-way ANOVA at T1 and T2, adjusted for age, sex, and measurements of Ba-N, representing the cranial base. Results of this adjusted analysis still showed highly statistically significant reductions in many mandibular skeletal measurements, and largely corroborated the results of the analysis without this adjustment. This further highlights that mandibular morphology in PRS is distinctly characteristic for this entity. Figures 7 and 8 show the cephalometric superimposition on Ba-N plane with the average tracing of the PRS group adjusted to match the length of Ba-N of the control group. The craniofacial features and morphology in PRS we described are the result of the anomaly itself, its inherent

American Journal of Orthodontics and Dentofacial Orthopedics June 2010

Fig 8. Cephalometric superimposition at T2 (basion-nasion), with PRS tracing adjusted to match length of Ba-N with control; 1 represents the location of RBS.

growth potential, the superimposed effects of surgical palate repair, scar tissue effects, and any potential airway and tongue posture effects. A previous study from our center, which compared mixed racial samples with PRS and those with isolated cleft palate at ages 5.6, 10.5, and 16.9 years reported significantly smaller SNB, smaller midface and mandibular lengths, and larger ANB, greater Wits value, and larger maxillary and mandibular plane angles in the PRS sample. Cranial base length, cranial base deflection, and SNA and gonial angles were similar at all 3 ages.38 In this study, we reported comparative information on the craniofacial pattern and growth of patients with PRS with that of a racially, sex, and age matched group of unaffected and untreated subjects and described their mandibular morphology and growth in detail at the age when comprehensive orthodontic treatment is most commonly conducted. The clinical implications of these comparative findings are therefore important to orthodontists. The retrognathic craniofacial pattern of PRS does not improve spontaneously during adolescence, and, considering the tendency for backward rotation and vertical growth, orthodontic mechanics should be used with care to avoid rotating the mandible back, which would further increase vertical height. The large reductions in body length at T2 (11.5%; 6.6 mm internal and 10.2 mm external) and chin thickness (10%) highlight that mandibular advancement

American Journal of Orthodontics and Dentofacial Orthopedics Volume 137, Number 6

surgery and genioplasty are likely to be indicated in the management of many patients. CONCLUSIONS

This retrospective longitudinal cephalometric study clarified the following features of the craniofacial morphology and adolescent facial growth in our sample with PRS. 1.

2. 3.

4.

5.

6.

7.

8.

Children born with nonsyndromic PRS had smaller cranial bases, bimaxillary retrognathism, and smaller maxillae and mandibles than unaffected children of similar age, sex, and racial background, when assessed at the prepubertal age of 11.7 years. The differences persisted during adolescence to become more evident at age 16.6 years. Their maxillary and mandibular planes were more steeply oriented to the cranial base. The deficiency in their mandibular size was evident at all regions: body height and length, ramal height and width, anterior basal width, and chin thickness. The greatest deficiency was in the body of the mandible, which led to a larger ramus-to-body ratio. Their mandibular flexure and gonial angles were relatively larger (open) before and after adolescent growth. Their growth pattern was more vertical with backward mandibular growth rotation, giving greater anterior facial and symphyseal height. Their anterior mandibular basal thickness underwent greater reduction compared with the unaffected controls during adolescent growth. The pattern of deficient mandibular growth established at age 11.7 years did not improve during pubertal growth; no greater differential adolescent catch-up growth was detected. With significantly reduced posterior face height, steep mandibular plane angle, and symphyseal uprighting, they remained retrognathic and retruded during adolescent growth. The effects of the small mandibles on their intermaxillary relationships were mitigated to a great extent by a small maxilla and severe bimaxillary retrognathism.

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