Pierre Robin sequence (PRS) is characterized by micrognathia, glossoptosis, and often airway compromise, which is frequently accompanied by a U-shaped cleft palate of varying severity, occurring in approximately 1 in 10,000 births (1). The sequence is termed non-syndromic PRS when it occurs without craniofacial syndrome (2). Micrognathia reduces tongue muscle support, leading to its descent into the subpharyngeal space, where it forms a spherical valve. While this valve permits exhalation, it obstructs inhalation, resulting in dyspnea as a significant manifestation of PRS (3). Micrognathia is typically defined as a visibly smaller mandibular body with mental retrusion (4). Identifying micrognathia from various perspectives is crucial for comprehensive patient care. Dental professionals can provide timely orthodontic intervention (1). Anesthesiologists need to be aware of micrognathia for effective airway management during intubation. Additionally, its impact on respiratory function necessitates monitoring and treatment of diseases such as obstructive sleep apnea (3).

However, not all visually diagnosed cases exhibit clinical symptoms. Researchers are divided on the extent to which the mandible undergoes proportional reduction before the growth spurt (5), with some suggesting a proportional reduction while others argue against it, citing ratios like ramus length to mandibular length (6). Certain aspects of this topic remain inconclusive. However, the quantitative characteristics of the maxillofacial region in PRS patients are not clearly understood.

Three-dimensional (3D) reconstruction using Mimics software involves converting two-dimensional medical images, such as computed tomography (CT) or magnetic resonance imaging (MRI), into detailed 3D models of anatomical structures. The Mimics software utilizes segmentation algorithms to delineate specific tissues or structures, allowing for accurate reconstruction and visualization. The advantages of its application in studies involving micrognathia include precise evaluation of craniofacial morphology, and enhanced surgical planning through virtual simulations. The Mimics software employs advanced segmentation algorithms to delineate specific tissues or structures, enabling accurate reconstruction and visualization. This capability allows clinicians to analyze complex anatomical relationships and assess treatment outcomes more effectively, ultimately leading to more personalized and effective patient care in the management of micrognathia (7).

Distinguished from other studies (8–10), quantitative distinctions in mandibular characteristics were identified by comparing certain alternative airway and mandibular parameters through 3D reconstruction using Mimics software. Given the absence of normal pediatric head CT data, the present study selected patients with non-syndromic isolated incomplete cleft palate (11) and normal mandibles as the control group. The objective of the present study was to compare the dentoskeletal characteristics of children diagnosed with non-syndromic PRS and those with cleft palate.

Initially, 59 PRS related cases were identified. Subsequently, cases were excluded based on predefined criteria, such as the presence of syndromic presentations (n = 13), patients with congenital heart disease or a history of undergoing surgery for congenital heart disease (n = 5), a combination of PRS with accessory tragus or polydactyly (n = 10), patients with a history of undergoing mandibular distraction osteogenesis (n = 12), and patient with incomplete electronic CT data (n = 5). As a result, a final sample of 14 PRS cases was finally included. 42 patients with isolated incomplete cleft palate were selected as the control group. The patient selection process is illustrated in Figure 1. The 3D reconstruction of dentoskeletal structures and facial soft tissue using Mimics software for both the PRS group and the control group was presented in Figures 2, 3.

The paired sample t-test indicated no significant difference between the first and second measurements in the repeated data (all P > 0.05). Additionally, an ICC value exceeding 0.90 demonstrated strong consistency among the experimental results (Supplementary Table S1).

No significant difference in age, gender and body weight was found between the PRS and control groups (Table 2). A point-Nasion-B point (ANB) angle was significantly greater in the PRS group compared with the control group (9.59 ± 3.51 vs. 5.45 ± 1.43, P = 0.002). The ratio of the linear distance between Articulare and Gonion (ArGo) to the linear distance between Gonion and Pogonion (GoPo) was significantly lower in the PRS group compared to the control group (0.48 ± 0.07 vs. 0.49 ± 0.03, P = 0.008). Additionally, the anteroposterior length (6.26 ± 2.28 vs. 8.96 ± 2.73 mm, P = 0.001) and area（75.74 ± 25.18 vs. 90.98 ± 27.68mm², P = 0.036）of the lower pharyngeal airway space (LPAS) were markedly reduced in the PRS group. The mandible volume, upper airway volume, full soft tissue convexity, Sella-Nasion-B point angle, Nasion-Sella-Gnathion angle, Frankfort-mandibular angle, gonial angle, ArGo, and GoPo exhibited no significant differences between the two groups (all P > 0.05) (Table 3).

This study revealed that the ANB angle, the ArGo/GoPO ratio and the anteroposterior length and area of LPAS could be valuable indicators for identifying micrognathia in patients with non-syndromic PRS. These parameters may represent potential markers for early diagnosis and monitoring of patient progress, warranting validation in further studies and clinical practice.

The ArGo/GoPo ratio of the PRS group was smaller than that of the control group, suggesting a disproportionate reduction in ArGo and GoPo. The mandibular ascending branch and the mandibular length exhibited disproportionate growth in the PRS group, with the mandibular ascending branch displaying slower development (6). The mandibular retraction and overall underdevelopment contributed to a narrow retro-lingual airspace. Mao and Ye (16) assessed the 3D changes in airway size and shape in newborns with isolated PRS who underwent mandibular distraction osteogenesis. They concluded that mandibular distraction osteogenesis in isolated PRS cases could enhance the size and configuration of the upper airway, confirming its effectiveness as a surgical intervention for alleviating airway obstruction in newborns with isolated PRS. Prior research (17) assessed the phonatory and morphological outcomes of 72 cognitively unimpaired adolescents with PRS. Morphological or phonatory impairments persisted in adolescents with PRS, although they did not appear to directly affect their quality of life. Adolescents, particularly those with non-isolated PRS, exhibited fragility in self-confidence and social relationships. European scholars assessed survival, hospitalization, and surgical procedures for children born with PRS across Europe (18). They found that infants with PRS experienced elevated mortality and morbidity rates, resulting in prolonged hospitalizations during their first year of life, with nearly all undergoing surgery before the age of five. However, survival rates improved beyond infancy, leading to decreased hospital admissions after reaching five years of age. Following cleft palate surgery, alterations in the patient's oropharynx volume within the airway are inevitable (19–21). Post-palatoplasty, the oropharyngeal airway mainly demonstrates transverse narrowing due to soft palate closure (22–24). Techniques, such as Fulow palatoplasty may further reduce transverse pharyngeal dimensions to achieve palatal elongation (25–27). Indirect evidence, such as postoperative stertor, suggests a reduction in patients' postoperative airway volume (28). Prior research highlighted that the original upper airway volume of children with PRS was lower than that of patients with similar clefts lacking micrognathia (29), alerting anesthesiologists to the elevated incidence of postoperative airway disorders in PRS patients. In a guideline for surgical management of neonates with PRS or severe micrognathia (30), CT was utilized to assess the structure and positioning of the tongue, as well as to delineate the relative placement of the inferior alveolar nerve upon entry into the mandible. Additionally, a CT scan aided in identifying the position of tooth buds and quantifying the minimum airway space (31). Han et al. (32) documented the utilization of allogenic acellular bone matrix and mandibular distraction osteogenesis in PRS cases and investigated the impact of distraction on the osteogenesis of acellular bone. They found that combining bilateral mandibular distraction osteogenesis with the placement of allogenic acellular bone in neonates represented safe and precise procedures, serving as the primary treatment modalities for severe PRS cases (32).

This study focused on exploring the digital diagnosis of micrognathia in non-syndromic PRS patients by integrating existing parameters established by other researchers. Our goal is to enhance the performance of digital models and provide valuable insights to the broader community. Digital models with high specificity indicators, combined with patient history, enable stomatologists and anesthesiologists to perform a more quantitative assessment of the airway before surgery, as opposed to relying solely on visual examination. This method is especially crucial developing countries.

The limitations of the present study should be pointed out. Firstly, the single-center, retrospective design of the study might introduce potential biases and incomplete data, such as missing information on head circumference, chest circumference, and head-to-body ratio. Secondly, the small sample size, particularly the reduced sample size for PRS due to missing electronic CT data, might limit the generalizability of the findings and increase the risk of type II errors. Finally, the study primarily concentrated on quantitative dentoskeletal characteristics, while qualitative aspects, such as functional outcomes or patient-reported measures were not assessed. Further large-scale prospective studies are warranted to overcome these limitations and provide more robust evidence.

In conclusion, this study concentrated on the dentoskeletal characteristics of non-syndromic PRS children compared with those with cleft palates, utilizing advanced imaging techniques and sophisticated software for analysis. The findings revealed significant differences in certain cephalometric parameters, particularly the ANB angle, the ArGo/GoPo ratio, and the anteroposterior length and area of LPAS between the PRS and control groups, highlighting the potential utility of these metrics as indicators for diagnosing micrognathia in non-syndromic PRS patients. Future research is required to validate these parameters.