Introduction
Cystic fibrosis (CF) is a genetic disorder affecting multiple systems and is often associated with nasal congestion, rhinorrhea, and mouth breathing because of upper respiratory tract involvement. These factors may influence craniofacial growth. This study aimed to evaluate craniofacial morphology in children with CF.
Methods
Fifty-six Turkish participants were included: 28 children with CF (14 boys and 14 girls; mean age = 12.10 ± 2.74 years) and 28 age- and sex-matched healthy controls (14 boys and 14 girls; mean age = 12.14 ± 2.74 years). Craniofacial features were assessed using cephalometric radiographs and maxillary digital models. Descriptive characteristics were compared using the chi-square test, and group differences were analyzed using the independent-samples t test.
Results
The sagittal skeletal classification revealed that patients with CF were 32.1% Class I, 35.7% Class II, and 32.1% Class III skeletal bases. Class I malocclusion was the most common (85.7%). In the control group, Class I skeletal relationships and malocclusion patterns were most prevalent (89.3%). Children with CF showed a statistically significant decrease in Ricketts maxillary width, and smaller SNA and SNB values (58.93 ± 3.55 mm, 79.51° ± 3.26°, and 76.43° ± 2.89°, respectively) than controls (64.03 ± 4.05 mm, 81.73° ± 2.60°, and 79.26° ± 2.47°, respectively). Conversely, the CF group had a higher Frankfort mandibular plane angle, a lower anterior facial height (LAFH), and LAFH% values (29.66° ± 2.90°, 66.0 ± 4.03 mm, and 57.09% ± 1.01%) than controls (25.91° ± 1.59°, 60.52 ± 2.67 mm, and 53.33% ± 1.16%). Digital model analysis showed a significantly reduced palatal width and palatal curvature angle (the mean difference was–2.36,–2.57,–3.06, and–3.77 mm for palatal width and–9.46°,–10.91°,–10.67°, and–11.67° for palatal curvature angle at the canine, first premolar, second premolar, and first molar teeth, respectively) and increased palatal depth (the mean difference was 0.41, 1.20, 1.64, 1.69 mm at the canine, first premolar, second premolar, and first molar regions, respectively), in the CF group ( P <0.05).
Conclusions
Children with CF exhibit altered craniofacial development, including bimaxillary retrusion and a constricted maxilla with a narrowed dental arch. Although the Frankfort mandibular plane angle and LAFH were statistically greater in patients with CF, these measurements were within normative limits, suggesting a tendency toward a vertically directed growth pattern. Future studies with a larger sample size can investigate this tendency.
Highlights
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The objective of this study was to evaluate craniofacial development in children diagnosed with cystic fibrosis (CF).
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Cephalometric analysis revealed a maxillary constriction and an increased vertical dimension in the CF group.
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In the model analysis, palatal width and palatal curvature angle measurements decreased, whereas palatal depth measurements increased in the CF group.
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Evaluation of children with CF in terms of craniofacial development may provide early detection of morphologic abnormalities.
Cystic fibrosis (CF) is a life-threatening genetic disease that affects approximately 1 in 3500 births and is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). , The CFTR gene encodes a protein that facilitates the transport of chloride and sodium across the apical membranes of epithelial cells, thereby regulating mucociliary secretions. Mutations in this protein result in the formation of thick, viscous secretions within the upper respiratory tract, which subsequently impair mucociliary clearance. This leads to reduced clearance of secretions and inflammation of the sinonasal mucosa. Chronic rhinosinusitis (CRS) and nasal polyposis are prevalent conditions affecting the upper respiratory tract of patients with CF. , The primary symptoms of CRS, namely nasal obstruction and mouth breathing, are frequently reported among patients with CF. ,,,,, Respiration, which normally occurs through the nose under physiological conditions, shifts to oral breathing in the presence of intranasal pathologies, such as chronic sinonasal infections, allergies, nasal polyposis, CRS, anatomic variations, and adenoid or tonsillar hypertrophy. Nasal breathing plays a crucial role in promoting the harmonious growth and development of the structures within the craniofacial complex. Prolonged mouth breathing can lead to alterations in the craniofacial tissues because of changes in the balance of forces acting on these tissues. Moreover, because children and adults with CF must adhere to a nutritionally balanced diet to ensure optimal growth and development, as maintaining optimal oral health is crucial to support adequate nutrient intake.
Today, the life expectancy of people with CF has increased significantly, and with early diagnosis and advanced treatment, the disease has become predominantly an adult condition rather than a childhood disease. Median survival has improved from 36.3 years in 2006 to 53.1 years in 2021. Upper respiratory disorders are common in CF and affect patients’ quality of life. A review of the existing literature reveals only 2 studies that have investigated the effect of CF on the craniofacial structures; however, these studies were limited to cephalometric analysis or small sample sizes. , Despite these findings, the orthodontic implications of CF-related craniofacial alterations remain largely underexplored, highlighting the need for early orthodontic assessment and multidisciplinary collaboration between pediatricians and orthodontists. The prevention of oral diseases is of paramount importance in this population, primarily because of the compromised immune function characteristic of patients with CF. Given the increased likelihood of an orthodontist encountering a patient diagnosed with CF, and conversely, the need for physicians to recognize the importance of referring patients with CF for orthodontic evaluation, the objective of this study was to comprehensively evaluate the impact of CF on the anteroposterior and transverse development of the maxilla, as well as the vertical development of the face. The null hypothesis is that there is no significant difference in craniofacial developmental patterns between subjects with CF and age- and sex-matched healthy controls.
Material and methods
The present prospective case-control observational study was approved by the clinical research ethics committee of Gaziantep University on 28 February 2024 (reference number: 2024/45). A power analysis using the G∗Power software (version 3.1.9.6; Franz Faul, Universtat Kiel, Kiel, Germany) indicated that a minimum sample size of 28 participants per group was required to detect a significant difference in maxillary intermolar width, assuming an effect size of 0.351, a standard deviation of 2.87, a statistical power of 0.80, and an alpha level of 0.05.
The study cohort comprised 28 pediatric Turkish patients with CF (14 boys and 14 girls; mean age = 12.10 ± 2.74 years) who were referred to the Department of Orthodontics, Faculty of Dentistry, Gaziantep University, and were followed in the outpatient clinics of the Pediatric Pulmonology and Pediatric Gastroenterology Departments of Gaziantep City Hospital. The CF group included children who had been diagnosed with CF based on either a sweat chloride concentration greater than 60 mEq/L or the identification of at least 2 CF-causing gene mutations. In most patients, genetic analyses were performed using targeted mutation panels or CFTR gene sequencing (either Sanger sequencing or next-generation sequencing). In instances in which large deletions or duplications were suspected, multiplex ligation-dependent probe amplification was performed. In addition, all patients had no coordination difficulties and had not received prior orthodontic treatment ( Fig 1 ).
The patient’s facial and intraoral photographs, along with the panoramic, posteroanterior cephalometric, and lateral cephalometric radiographs.
An equal number of healthy Turkish controls, matched to the CF group by cervical maturation and sex (14 boys and 14 girls; mean age = 12.14 ± 2.74 years), were selected from all consecutive orthodontic patients at the Department of Orthodontics based on these matching criteria ( Table I ). The control group included children with Class I minimal crowding, with no history of systemic disease, syndrome, anomaly, or allergy. Subjects with a history of previous orthodontic treatment or poor-quality radiographs or digital models were excluded. Cervical maturation was assessed using lateral cephalometric radiographs according to the cervical vertebral maturation method of Bacetti et al. A consent form was signed by patients and their parents, indicating their agreement to participate in the study.
Table I
Descriptive characteristics of patients diagnosed with CF and the control group
| CF (n = 28) | Control (n = 28) | P value | ||||
|---|---|---|---|---|---|---|
| Number | % | Number | % | |||
| Gender | Girls | 14 | 50.0 | 14 | 50.0 | 1.000 |
| Boys | 14 | 50.0 | 14 | 50.0 | ||
| Cervical maturation | CS2 | 8 | 28.5 | 8 | 28.5 | 1.000 |
| CS3 | 6 | 21.4 | 6 | 21.4 | ||
| CS4 | 7 | 25.0 | 7 | 25.0 | ||
| CS5 | 7 | 25.0 | 7 | 25.0 | ||
| Mean ± SD (min-max) | Mean ± SD (min-max) | |||||
|---|---|---|---|---|---|---|
| Age t | 12.10 ± 2.74 (8.0-16.0) | 12.14 ± 2.74 (7.5-16.0) | 0.958 | |||
| Gender | Girls | 11.43 ± 2.64 (8.0-15.5) | 11.43 ± 2.68 (7.5-16.0) | |||
| Boys | 12.77 ± 2.78 (9.0-16.0) | 12.85 ± 2.72 (7.83-16.0) | ||||
χ 2, Chi-square test (categorical data); t , independent-samples t test; min , minimum; max , maximum; SD , standard deviation, CS , cervical vertebral maturation stage.
The data for the present study were gathered from cephalometric radiographs and digital models obtained from the participating patients. Lateral and posteroanterior (PA) cephalograms for this study were taken using the Planmeca Promax 2D (Planmeca OY, Finland). The angles and distances in the lateral and PA cephalometric radiographs measured in the present study are illustrated in Figure 2 , A and B . In brief, the SNA, SNB, and ANB angles were measured from lateral cephalometric radiographs to evaluate the sagittal relationships (Class I tendency: ANB 2°-4°; Class II tendency: ANB >4°; and Class III tendency: ANB <2°); the Frankfort mandibular plane (FMA) angle, lower anterior facial height (LAFH), and LAFH% were measured to evaluate vertical relationship; overjet was measured to classify the malocclusion according to the incisor bases malocclusion classification, (Class I: OJ = 1-4 mm and OB was normal; Class II: OJ >4 mm; and Class III: OJ <1 mm) and the Ricketts maxillary width (MW), defined as the distance between the intersection points of the zygomatic arch and maxillary tuberosity on the right and left jugal processes (MW), was measured from PA cephalometric radiographs to evaluate the transverse relationships. A total of 56 lateral and 56 PA cephalometric radiographs were traced by N.G.E. using the Dolphin Imaging program (Dolphin Imaging, Chatsworth, Calif).
A , Cephalometric analysis: 1. SNA (°): the angle between the sella-nasion plane and the line passing through the nasion-A point; 2. SNB (°): the angle between the sella-nasion plane and the line passing through the nasion-B point; 3. ANB (°): the angle between the N-A line and the N-B line; 4. FMA (°): the angle formed between the Frankfort horizontal plane and the mandibular plane (Go-Me); and 5. LAFH (mm): lower anterior facial height. The distance between the anterior nasal spine and the menton points; B, PA analyses: 6. AFH (mm): anterior facial height. The distance between the nasion and menton; and 7. MW (mm): maxillary width: the distance between the intersection points of the zygomatic arch and the maxillary tuberosity on the right and left jugal processes (according to Ricketts).
Digital models were acquired using an intraoral scanner (Trios 3 Move+, 3Shape Trios A/S, Copenhagen, Denmark), with a resolution of 20 μm. A total of 12 measurements (4 widths, 4 heights, and 4 angles) were obtained using Ortho Analyzer (3Shape, Copenhagen, Denmark) by identifying 14 points on the digital maxillary models. A gingival plane was defined by joining the center of the dentogingival junction of all teeth ( Fig 3 , A ). The measurements performed after the gingival plane was created are shown in Figure 3 , B . Briefly, a series of linear and angular measurements were performed at 4 transverse levels to facilitate a comprehensive 3-dimensional evaluation of the palatal vault in terms of width, height, and shape across the various dental levels. These levels corresponded to the canine, first premolar, second premolar, and first molar regions. The transverse distances (D3-D6) were defined as the width of the palate and measured as the distances between the centers of the dentogingival junctions of the right and left teeth at each level. The vertical heights (H3-H6) were measured as the perpendicular distance from the line connecting the dentogingival junctions of the corresponding teeth to the highest point of the palatal vault along the midpalatal suture, reflecting palatal depth. The angular measurements (A3-A6) were calculated as the angles formed between the line connecting the dentogingival junctions of the right and left teeth and the line extending from this connection to the highest point of the palatal vault on the midpalatal suture. An increase in the angle indicates a narrower palate, whereas a decrease corresponds to a deeper palatal vault. These angular measurements are indicative of palatal curvature.
A , Before palatal analysis, a gingival plane was defined by joining the centers of the dentogingival junction of all teeth; B, Analysis of the palatal surface (D3: the distance between the centers of the dentogingival junction of the maxillary right and left canines; D4: maxillary right and left first premolars; D5: maxillary right and left second premolars; D6: maxillary right and left first molars; H3: the distance between the line connecting the centers of the dentogingival junction of the maxillary right and left canines and the highest point of the palatal vault at the midpalatal suture; H4: maxillary right and left first premolars; H5: maxillary right and left second premolars; H6: maxillary right and left first molars; A3, the angle between the line joining the centers of the dentogingival junction of the maxillary right and left canines and the highest point of the palatal vault on the midpalatal suture; A4: maxillary right and left first premolars; A5: maxillary right and left second premolars; and A6: maxillary right and left first molars).
Statistical analyses
A chi-square test was used to compare the descriptive characteristics of the children in the CF and control groups. Independent-samples t tests were used to compare the cephalometric and digital model measurements between the CF and control groups, as well as between gender subgroups, which were normally distributed. The assumptions of normality and homogeneity of variances were tested using the Shapiro-Wilk and Levene tests, respectively. The data were analyzed using SPSS (version 22.0; IBM, Armonk, NY). Statistical significance was set at P <0.05
The same investigator retraced all the radiographs and repeated the model analyses after a 3-week interval to assess the intraexaminer reliability of measurements. The measurements obtained from the same patient at different time points were assessed using the Pearson correlation coefficient (r). The r values ranged 0.987-1.000, indicating an excellent level of consistency in intraexaminer measurement.
Results
Patients with CF exhibited a heterogeneous distribution of skeletal pattern distribution, with 32.1% Class I, 35.7% Class II, and 32.1% Class III–tendency; Class I malocclusion was the most prevalent (85.7%), followed by Class II (7.1%), and Class III (3.6%). Controls showed a Class I skeletal pattern, with Class I malocclusion being the most common (89.3%) and Class III malocclusion observed only in 3 patients.
Children with CF showed a statistically significant reduction in Ricketts maxillary width, and smaller SNA and SNB angles (58.93 ± 3.55 mm, 79.5°1 ± 3.26°, and 76.43° ± 2.89°, respectively) than controls (64.03 ± 4.05 mm, 81.73° ± 2.60°, and 79.26° ± 2.47°, respectively). Conversely, the CF group had higher FMA, LAFH, and LAFH% values (29.66° ± 2.90°, 66.0 ± 4.03 mm, and 57.09% ± 1.01%, respectively) than controls (25.91° ± 1.59°, 60.52 ± 2.67 mm, and 53.33% ± 1.16%, respectively). In intragroup comparisons, the LAFH, LAFH%, and MW of boys with CF were higher than those of the girls ( Table II ).
Table II
Results of the cephalometric measurements of CF and controls
| SNA (°) | SNB (°) | ANB (°) | FMA (°) | LAFH (mm) | LAFH (%) | MW (mm) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean ± SD | P value | Mean ± SD | P value | Mean ± SD | P value | Mean ± SD | P value | Mean ± SD | P value | Mean ± SD | P value | Mean ± SD | P value | |
| CF (n = 28) | 79.51 ± 3.26 | 0.007 | 76.43 ± 2.89 | 0.000 | 3.22 ± 2.49 | 0.172 | 29.66 ± 2.90 | 0.000 | 66.00 ± 4.03 | 0.000 | 57.09 ± 1.01 | 0.000 | 58.93 ± 3.55 | 0.000 |
| Control (n = 28) | 81.73 ± 2.60 | 79.26 ± 2.47 | 2.45 ± 1.52 | 25.91 ± 1.59 | 60.52 ± 2.67 | 53.33 ± 1.16 | 64.03 ± 4.05 | |||||||
| CF girls (n = 14) | 79.59 ± 3.25 | 0.102 | 76.42 ± 2.87 | 0.011 | 3.42 ± 2.41 | 0.204 | 30.05 ± 3.23 | 0.000 | 63.70 ± 2.22 | 0.000 | 56.47 ± 0.41 | 0.000 | 57.15 ± 3.00 | 0.001 |
| CF girls (n = 14) | 81.41 ± 2.36 | 79.04 ± 2.1 | 2.35 ± 1.91 | 26.01 ± 1.52 | 59.20 ± 1.81 | 52.89 ± 0.84 | 61.50 ± 2.81 | |||||||
| CF boys (n = 14) | 79.44 ± 3.39 | 0.037 | 76.44 ± 3.01 | 0.011 | 3.01 ± 2.65 | 0.554 | 29.34 ± 2.49 | 0.000 | 68.30 ± 4.17 | 0.000 | 57.72 ± 1.06 | 0.000 | 60.72 ± 3.21 | 0.000 |
| CF boys (n = 14) | 82.04 ± 2.87 | 79.49 ± 2.85 | 2.56 ± 1.07 | 25.82 ± 1.71 | 61.85 ± 2.79 | 53.76 ± 1.30 | 66.57 ± 3.50 | |||||||
| CF girls (n = 14) | 79.59 ± 3.25 | 0.901 | 76.42 ± 2.87 | 0.985 | 3.42 ± 2.41 | 0.674 | 30.05 ± 3.23 | 0.496 | 63.70 ± 2.22 | 0.001 | 56.47 ± 0.41 | 0.000 | 57.15 ± 3.00 | 0.005 |
| CF boys (n = 14) | 79.44 ± 3.39 | 76.44 ± 3.01 | 3.01 ± 2.65 | 29.34 ± 2.59 | 68.30 ± 4.17 | 57.72 ± 1.06 | 60.72 ± 3.21 | |||||||
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