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INTRODUCTION
Pierre-Robin sequence (PRS) is a congenital anomaly characterized by micrognathia, glossoptosis, varying degrees of respiratory difficulties, and cleft palate (CP).1-4 Most clinical research on PRS has focused on managing respiratory complications,5-8 evaluating the mandibular size and morphology,3,7,9,10 and examining the potential for mandibular catch-up growth.4,11-14
Figueroa et al.15 observed that, during the first 2 years of life, accelerated mandibular growth, slower tongue growth, and a more anterior tongue posture improved airway dimensions, resolving respiratory distress despite the persistence of suboptimal airway dimensions. Similarly, Staudt et al.2 reported significant increases in the nasopharyngeal and velopharyngeal airway dimensions at the age of 5, 10, 15, and 20 years, which were attributed to recession of adenoid and anterior repositioning of the tongue during growth. However, this study did not divide the subjects according to the diverse skeletal patterns observed at their initial examination.
In pre-adolescent PRS patients, the most common skeletal characteristics include a Class II relationship, posteriorly positioned maxilla and mandible, hyperdivergent growth pattern, obtuse gonial angle, and a reduced mandibular body to anterior cranial base length ratio (MBL/ACBL [Go-Me/S-N]).3 Despite these consistent features, clinical management remains challenging due to (1) considerable variation in the sagittal and vertical skeletal phenotypes, (2) persistence of original skeletal patterns from age 8 to 13,3,4 and (3) the need to investigate the PRS patients who did not undergo functional or orthopedic treatment or surgical intervention.
To our knowledge, no previous studies have explored longitudinal changes in the skeletal patterns in the maxillomandibular complex and the upper airway dimensions in Korean pre-adolescent PRS patients. Therefore, this retrospective study aims to investigate the changes in upper airway dimensions in growing PRS patients based on the skeletal pattern of the maxillomandibular complex.
MATERIALS AND METHODS
This retrospective study included Korean patients with PRS who visited the Department of Orthodontics at Seoul National University Dental Hospital (SNUDH), Seoul, Republic of Korea. The inclusion criteria were as follows: (1) patients diagnosed with PRS and CP to ensure sample homogeneity,4,10,16 (2) patients treated or followed longitudinally by a single orthodontist (SHB) between 2005 and 2024, (3) patients with complete records, including charts, clinical photographs, cephalometric and panoramic radiographs and (4) patients with lateral cephalograms taken at ages of 7–10 years (T0) and 12–15 years (T1). During acquisition of lateral cephalograms, patients were instructed to maintain a natural head position, gently occlude after swallowing, and hold their breath at the end of expiration.17 The exclusion criteria were as follows: (1) patients with major cerebral disturbances or myodystrophy; and (2) patients with a history of adenoidectomy, velopharyngeal surgery, functional or orthopedic treatment, or surgical intervention including mandibular distraction osteogenesis, between T0 and T1. These criteria were applied to eliminate potential confounding factors influencing the maxillomandibular skeletal pattern or upper airway dimension.18 This study was reviewed and approved by the Institutional Review Board of the SNUDH (ERI24021).
Ultimately, the final samples consisted of 23 growing patients with PRS (7 boys and 16 girls; mean ages: T0 = 8.81 years, T1 = 14.05 years; mean follow-up duration: 5.23 years, Table 1).
The skeletal and upper airway landmarks and variables analyzed are summarized in Figures 1, 2 and Table 2. As the CP type (soft palate cleft or hard palate cleft) showed no significant correlations with any cephalometric variables in PRS patients,3 subjects were not further subdivided by CP type. Cephalometric norms and standard deviation (SD) were used to evaluate the severity of the maxillomandibular skeletal discrepancy, referencing the cephalometric analysis chart of the Department of Orthodontics, SNUDH, and previous findings (−1 SD < normal ≤ 1 SD; 1 SD < moderately large ≤ 2 SD; −2 SD < moderately small ≤ −1 SD; 2 SD ≤ very large; very small ≤ −2 SD).4
Based on the SNB value at T0 (Criteria, –2 SD), the final sample was divided into the very retrusive mandible group (Group 1: SNB more severe than –2 SD; n = 13; 4 boys and 9 girls, mean ages: T0 = 8.87 years, T1 = 13.74 years; mean follow-up duration: 4.87 years) and the moderately retrusive mandible group (Group 2: SNB less severe than –2 SD; n = 10; 3 boys and 7 girls, mean ages: T0 = 8.67 years, T1 = 14.19 years; mean follow-up duration: 5.53 years). The skeletal and upper airway variables at T0 and T1 were compared between Groups 1 and 2. Additionally, changes in these variables (∆T1–T0) within and between the Groups were analyzed. Normal values for upper airway dimensions were referenced from a young adult normal group by Cho et al.19 In addition, correlations between the skeletal and upper airway variables were also investigated.
To assess measurement reliability, all cephalometric parameters of five randomly selected subjects were re-measured by the same operator (SJY) at 2-week intervals. Measurement error was evaluated using the Dahlberg formula. The mean Dahlberg error was 0.89 mm (range: 0.33–1.9 mm) and 1.18 degrees (range: 0.18–2.96 degrees). As the errors were within acceptable limits, the first set of measurements was used for further analysis.
Statistical analyses, including descriptive statistics, Mann–Whitney U test, Wilcoxon’s signed rank test, chi-square test, and Pearson’s correlation analysis, were performed using SPSS software (version 12.0; SPSS Inc., Chicago, IL, USA). Statistical significance was set at P < 0.05.
RESULTS
Comparison of the demographic data (Table 1)
No significant differences were observed in distribution of sex and cervical vertebral maturation index, age at T0 and T1, or duration of follow-up (T0-T1) between Groups 1 and 2.
Comparison of the skeletal variables between Groups 1 and 2 (Tables 3–5)
At T0, Group 1 exhibited a more retrusive maxilla and mandible, as well as a more hyperdivergent pattern compared to Group 2. At T1, Group 1 maintained a significantly more retrusive maxilla and mandible relative to Group 2. During T0-T1, both Groups demonstrated increases in posterior facial height and mandibular body length and decreases in gonial angle. However, there was no significant difference in ΔT1–T0 between the two groups, suggesting that the initial difference might be maintained.
Comparison of the upper airway variables between Groups 1 and 2 (Tables 3–5)
At T0, Group 1 exhibited a more posteriorly positioned hyoid bone and larger superior and inferior pharyngeal airway space (IPAS) compared to Group 2. At T1, Group 1 showed less forward tongue positioning and a more obtuse soft palate angle (SPA) relative to Group 2. However, the differences in H-PTV, superior pharyngeal airway space (SPAS), and IPAS between the two groups at T1 were not statistically significant, suggesting that the initial differences would diminish over time.
Between T0 and T1, both Groups showed increases in the hyoid-symphysis distance, tongue length (TGL), and pharyngeal airway spaces. Additionally, the changes in upper airway variables were similar between the two groups, except for soft palate length (SPL). These findings suggest that forward mandibular growth and the repositioning of the tongue and hyoid bone result in comparable increases in pharyngeal airway space variables for both groups.
Linear regression analysis (Appendix Tables 1 and 2)
When analyzing all subjects collectively, SNB showed significant positive correlations with H-PTV, TGL, SPAS, MPAS, and IPAS at T0 and with TT-PTV and SPA at T1. These findings suggest that the severity of the retrognathic mandible worsens, the smaller values of the upper airway parameters appear.
Correlations between the skeletal and upper airway variables (Tables 6 and 7)
The results of the multiple regression analysis of correlations between the skeletal and upper airway variables can be summarized as follows: forward growth of the maxilla, an increase in mandibular plane steepness, and a larger gonial angle may contribute to forward tongue positioning, ultimately increasing pharyngeal airway dimensions. Regarding correlations between upper airway variables, changes in ΔTGL, ΔSPL, and ΔSPA showed positive correlations with changes in superior and middle pharyngeal airway spaces (∆SPAS and ∆MPAS). These results indicate that the forward tongue repositioning and the change in the length and configuration of the soft palate might indirectly increase the superior and middle pharyngeal airway space. SPL showed a positive correlation with PNS-ad1, suggesting that changes in the soft palate during pubertal growth may be related to adenoid tissue atrophy. Furthermore, repositioning of the tongue and hyoid bone (∆TGL, ∆TT-PTV, and ∆H-RGN) might indirectly induce an increase in the vertical airway length (∆VAL).
DISCUSSION
This study has several strengths in its design: (1) To ensure sample homogeneity, only growing patients with PRS and CP were included; (2) To avoid confounding factors affecting the skeletal pattern of the maxillomandibular complex and the upper airway dimension, patients who had not undergone growth modification therapy (e.g., functional or orthopedic therapy) or surgical intervention (e.g., mandibular distraction osteogenesis) were recruited; and (3) The longitudinal follow up spanned a mean duration of 5.2 years, capturing changes from pre-adolescent to adolescent period.
Comparison of the skeletal variables between Groups 1 and 2 (Tables 3–5)
At both T0 and T1, Groups 1 and 2 exhibited skeletal Class II malocclusion and a hyperdivergent pattern. However, Group 1 maintained a more retrusive maxilla and mandible compared to Group 2 at T1. Between T0 and T1, both groups showed significant growth in mandibular body length and ramus height and a decrease in gonial angle. Despite this growth, neither group demonstrated significant changes in SNA, SNB, ANB, or SN-MP at T0-T1. These findings align with those of Baek et al.,4 who reported that the original skeletal patterns observed at 8 years of age in pre-adolescent patients with PRS remained relatively unchanged by 13 years of age. Furthermore, the skeletal variables at T2, including SNA, SNB, ANB, and SN-MP, did not achieve normal values for the ethnic population, particularly in Group 1.
Comparison of the upper airway variables between Groups 1 and 2 (Tables 3–5)
At T0, Group 1 exhibited a more retrusive maxilla and mandible and a more hyperdivergent pattern compared to Group 2, resulting in a more posteriorly positioned hyoid bone. However, the finding that Group 1 also had larger superior and IPAS suggests the presence of a compensatory response to skeletal deficiencies aimed at maintaining upper airway patency.
At T1, despite more retrusive maxilla and mandible, less forward positioning of tongue, and more obtuse SPA in Group 1 compared to Group 2, the sizes of SPAS and IPAS did not differ significantly between the two groups. These findings may indicate maintenance of the compensatory mechanism to obtain upper airway patency in Group 1.
Between T0 and T1, both groups exhibited significant increases in TGL and pharyngeal airway spaces, consistent with the findings of Staudt et al.2 They reported a significant increase in nasopharyngeal and velopharyngeal airway dimensions in children with PRS, attributed to anterior tongue repositioning and adenoid recession.2
These findings suggest that, although upper airway dimensions remained below normal values, growth of the mandibular body length and ramus height in patients with PRS may help reposition the tongue and hyoid bone, leading to an increase in pharyngeal airway spaces. In contrast to the skeletal variables, changes in upper airway dimensions were similar between Groups 1 and 2, except for SPL. This might be related to the maintenance of the compensatory mechanisms for obtaining upper airway patency in Group 1.
Correlations between skeletal and upper airway variables (Tables 6 and 7)
The results of the multivariate regression analysis suggest that growth of the maxilla, changes in vertical skeletal patterns and gonial angle, changes in the superior and middle airway space, and the position or size of the tongue, hyoid bone, and soft palate, and atrophy of the adenoid could be interrelated. Ultimately, these factors appear to contribute to an increase in pharyngeal airway dimensions.
Clinical implications
This study provides preliminary data on upper airway changes in growing patients with PRS, which could be valuable for establishing individualized diagnosis and treatment planning. Forward growth and counterclockwise rotation of the mandible are critical for repositioning the tongue and hyoid bone and enhancing upper airway dimensions. These findings highlight the importance of vertical growth control and growth modification therapy during pre-adolescent and adolescent growth periods. In cases of severe airway obstruction, surgical intervention such as mandibular distraction osteogenesis could be considered immediately after the pubertal growth peak.
The limitations of this study include. (1) A relatively small sample size derived from a single institution, (2) The absence of an untreated normal control group with a skeletal Class I pattern and longitudinal follow-up data, (3) assessment of the upper airway using two-dimensional lateral cephalometric analysis, and (4) the lack of polysomnographic (PSG) data, to corroborate the findings. Future studies should incorporate a three-dimensional evaluation of the upper airway in a multicenter case-control design. This would require a larger sample size, advanced imaging techniques such as 3D-computed tomography or cone-beam computed tomography, and PSG data for comprehensive validation of the results.
CONCLUSIONS
The findings of this study indicate that, even in growing PRS patients with a severely retrusive mandible, upper airway spaces increased due to (1) forward growth of the mandible and repositioning of the tongue and hyoid bone, and (2) a compensatory mechanism addressing skeletal deficiency to maintain upper airway patency.
However, further research is necessary to confirm these findings.
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