Abstract
Background
Cleidocranial dysplasia (CCD) is a rare inherited skeletal disorder characterized by distinctive skeletal and dental abnormalities, often leading to delayed or missed diagnosis. Dental findings are frequently the most prominent clinical features and may play a key role in identifying the condition.
Case presentation
A 16-year-old girl presented with missing permanent teeth, impaired mastication and esthetic concerns. The patient had previously been diagnosed with growth delay despite normal endocrine evaluation, including growth hormone stimulation testing. The diagnosis of CCD was suspected during dental examination based on characteristic clinical and radiographic features. Clinical assessment revealed short stature, clavicular hypoplasia with shoulder hypermobility and typical craniofacial features. Intraoral findings included prolonged retention of primary teeth, delayed eruption of permanent dentition and Class III malocclusion. Radiographic and CBCT imaging confirmed multiple impacted and supernumerary teeth, delayed cranial suture closure and additional skeletal abnormalities consistent with CCD.
A conservative, stage-based treatment approach was adopted to coordinate future surgical and orthodontic interventions according to skeletal maturity. A removable partial denture (RPD) was provided as an interim solution, resulting in improved mastication, speech and esthetics.
Conclusion
This case emphasizes the important role of dental professionals in recognizing undiagnosed systemic conditions such as CCD. Early identification based on dental findings and appropriate timing of intervention are essential for optimizing functional and esthetic outcomes.
Keywords: Cleidocranial dysplasia, Case report, Supernumerary teeth, Delayed tooth eruption, Multidisciplinary management, Radiographic imaging, Prosthetic rehabilitation
Background
Cleidocranial dysplasia (CCD) is a rare inherited skeletal disorder with an estimated prevalence ranging from approximately 1 to 9 per 1,000,000 individuals worldwide [1]. Variability in reported prevalence rates may reflect differences in diagnostic criteria, genetic testing availability and underdiagnosis of milder cases.
Despite its low frequency, CCD is clinically important due to its characteristic combination of skeletal and dental abnormalities, which may remain unrecognized for extended periods. In regions with limited epidemiological data, including Kosovo, the apparent absence of reported cases may reflect underdiagnosis rather than true rarity.
CCD is an autosomal dominant condition with high penetrance and variable expressivity, meaning that affected individuals may present with a wide range of clinical manifestations, even within the same family [2, 3]. This variability often complicates diagnosis, particularly when skeletal or dental findings are assessed in isolation.
The disorder is primarily caused by heterozygous mutations in the RUNX2 gene, located on chromosome 6p21, which encodes a key transcription factor essential for osteoblast differentiation, bone formation and tooth development and plays a central role in skeletal and dental morphogenesis [2, 3]. RUNX2 also functions as a critical regulator of both intramembranous and endochondral ossification. Loss-of-function mutations, most commonly due to haploinsufficiency, disrupt normal skeletal development and result in the characteristic features of CCD [4]. However, approximately 20–30% of clinically diagnosed cases do not show identifiable RUNX2 mutations, suggesting genetic heterogeneity or the involvement of additional molecular mechanisms [5].
Recent studies have demonstrated a broad spectrum of RUNX2 variants and genotype-phenotype correlations, with certain mutations being associated with more pronounced dental and craniofacial manifestations [6–8]. Nevertheless, the relationship between genotype and phenotype remains complex and clinical variability is influenced by additional genetic, epigenetic and environmental factors.
Skeletal manifestations commonly include hypoplastic or absent clavicles, delayed closure of cranial sutures, frontal bossing and short stature. Dental abnormalities are highly prevalent and include prolonged retention of primary teeth, delayed or failed eruption of permanent dentition and multiple supernumerary teeth. These findings are closely related to altered bone remodeling and disturbed eruption mechanisms associated with RUNX2 dysfunction.
Because dental features are often among the earliest and most prominent signs of the disorder, careful clinical and radiographic evaluation is essential for timely diagnosis. Recognition of this characteristic pattern is particularly important in patients presenting with unexplained growth delay or persistent eruption disturbances.
The aim of this case report is to present a patient with cleidocranial dysplasia characterized by complex dental and skeletal manifestations, to emphasize the role of dental findings in early diagnosis and to highlight the importance of a multidisciplinary, stage-based treatment strategy aligned with skeletal maturity.
Case presentation
A 16-year-old girl was referred to the Department of Orthodontics with the chief complaint of missing permanent teeth and dissatisfaction with her dental appearance. She also reported mild difficulty with mastication but denied pain, swelling or any history of dental trauma.
Her medical history was notable for previously documented growth delay.
Given the history of growth delay, the patient underwent pediatric endocrine evaluation to rule out endocrine causes of short stature, including growth hormone (GH) deficiency. Growth hormone stimulation testing demonstrated a normal hormonal response, with peak GH levels exceeding 10 ng/mL (reference range: peak GH > 10 ng/mL) (Table 1).
Table 1.
Growth hormone stimulation test results
| Time (min) | Blood glucose (mmol/L) | GH (ng/mL) |
|---|---|---|
| 0 | 6.5 | 3.0 |
| 20 | 4.4 | 6.4 |
| 30 | 4.8 | 11.5 |
| 60 | 3.9 | 14.8 |
| 90 | 4.8 | 11.9 |
| 120 | 5.7 | 5.8 |
Peak GH level exceeded 10 ng/mL, indicating a normal response
This finding excluded endocrine causes of short stature and prompted further consideration of an underlying systemic or genetic condition. There was no known family history of similar skeletal or dental conditions.
The patient was otherwise in good general health, was not taking any medications and reported no known allergies. General physical examination revealed short stature and a slender body habitus. A notable clinical finding was marked shoulder hypermobility, allowing approximation of the shoulders toward the midline, consistent with clavicular hypoplasia (Fig. 1).
Fig. 1.
Clinical photographs demonstrating shoulder hypermobility due to hypoplastic clavicles. A Frontal view showing approximation of the shoulders toward the midline. B Lateral view illustrating reduced clavicular contour
Craniofacial examination revealed frontal bossing, mild hypertelorism, a depressed nasal bridge, midface hypoplasia and mandibular prognathism (Fig. 2).
Fig. 2.
Craniofacial features associated with cleidocranial dysplasia. A Frontal view demonstrating frontal bossing, hypertelorism and depressed nasal bridge. B Lateral profile showing midface hypoplasia and mandibular prognathism
Intraoral examination showed a high-arched and narrow palate, prolonged retention of primary teeth, delayed eruption of permanent dentition and a Class III malocclusion (Fig. 3).
Fig. 3.
Intraoral findings. A Frontal intraoral view showing prolonged retention of primary teeth and Class III malocclusion. B Maxillary occlusal view demonstrating a high-arched and narrow palate
Examination of the extremities revealed dysplastic fingernails and shortened, malformed phalanges (Fig. 4). In addition, mild postural asymmetry with subtle thoracic kyphosis was observed (Fig. 5). Bilateral knee alignment changes suggestive of genu valgum were also noted (Fig. 6).
Fig. 4.
Examination of the hands. A, B Clinical images demonstrating dysplastic fingernails and shortened, malformed phalanges, consistent with skeletal dysplasia
Fig. 5.
Clinical photograph showing mild postural asymmetry and subtle thoracic kyphosis
Fig. 6.
Lower limb examination demonstrating bilateral knee alignment changes suggestive of genu valgum
Radiographic and imaging findings
Radiographic evaluation was performed to assess both dental and skeletal abnormalities and to support diagnostic clarification.
Panoramic radiography (orthopantomogram) revealed multiple impacted permanent teeth and numerous supernumerary teeth in both the maxilla and mandible. Features suggestive of increased gonial angle width and maxillary sinus morphology were also observed (Fig. 7).
Fig. 7.
Panoramic radiograph showing multiple impacted permanent teeth and supernumerary teeth, with features suggestive of increased gonial angle width and maxillary sinus morphology
Cone-beam computed tomography (CBCT) was utilized to provide a three-dimensional assessment of the craniofacial structures. This modality enabled precise visualization of the number, position and orientation of impacted and supernumerary teeth, as well as their spatial relationship with adjacent anatomical structures, including the inferior alveolar nerve and maxillary sinus (Fig. 8).
Fig. 8.
Cone-beam computed tomography (CBCT) images demonstrating multiple impacted and supernumerary teeth. The three-dimensional reconstruction highlights their spatial relationship with adjacent anatomical structures, including the inferior alveolar nerve
A chest radiograph confirmed hypoplastic clavicles and mild thoracic spinal curvature (Fig. 9). Hand and wrist radiographs demonstrated metacarpal pseudoepiphysis and shortened phalanges (Fig. 10). Posteroanterior skull radiographs showed delayed closure of cranial sutures and the presence of wormian bones, consistent with delayed ossification (Fig. 11).
Fig. 9.
Chest radiograph demonstrating hypoplastic clavicles and mild thoracic spinal curvature
Fig. 10.
Hand and wrist radiographs. A Metacarpal pseudoepiphysis. B Shortened phalanges, consistent with skeletal dysplasia
Fig. 11.
Skull radiographs. A Posteroanterior view showing delayed cranial suture closure and wormian bones. B Lateral cephalometric image demonstrating maxillary hypoplasia and mandibular prognathism
Diagnosis
Based on the comprehensive clinical and radiographic findings, a diagnosis of cleidocranial dysplasia (CCD) was established. The combination of hypoplastic clavicles, delayed cranial ossification, multiple impacted and supernumerary teeth and characteristic craniofacial features strongly supported this diagnosis.
Chromosomal analysis demonstrated a normal female karyotype (46,XX), thereby excluding major chromosomal abnormalities associated with growth and skeletal disorders that may present with overlapping clinical features.
Molecular genetic testing for RUNX2 mutations was not performed due to the limited availability of genetic diagnostic resources, representing a limitation of the present case. Nevertheless, the diagnosis was strongly supported by the highly characteristic clinical and radiographic presentation, which is widely accepted as sufficient for the clinical diagnosis of CCD [2, 3].
Treatment and management
The management plan was developed based on the patient’s age, skeletal maturity, extent of dental impaction and overall craniofacial characteristics.
Radiographic findings revealed multiple impacted permanent and supernumerary teeth, as well as incomplete root formation of several unerupted teeth. In addition, the presence of a high-arched and narrow palate further complicated the treatment approach, as it may require future orthodontic and possibly surgical expansion. At this stage, no active expansion intervention was performed, as definitive expansion procedures were deferred until completion of skeletal growth to ensure greater stability and predictability of outcomes.
Several treatment protocols described in the literature advocate early surgical exposure combined with orthodontic traction to facilitate eruption of impacted teeth and improve occlusal development. However, these approaches may require multiple surgical procedures, prolonged orthodontic treatment and high patient compliance. In the present case, early surgical exposure and orthodontic traction were carefully considered but were not selected as the initial treatment approach due to the extent of dental impaction, ongoing skeletal development and the patient’s immediate functional and esthetic concerns.
Patient-related factors, including significant anxiety regarding extensive surgical intervention, were also considered during treatment planning and supported the decision to initially adopt a conservative staged approach.
For these reasons, a conservative, stage-based management strategy was adopted. This approach was selected to allow appropriate timing and coordination of future surgical and orthodontic interventions, including the planned extraction of supernumerary teeth and the possibility of implant-supported rehabilitation after completion of skeletal growth. The decision was further supported by clinical assessment of skeletal maturity, indicating ongoing growth.
Definitive surgical intervention, including extraction of supernumerary teeth and orthodontic traction of impacted teeth, was therefore postponed to achieve more predictable and stable long-term outcomes.
At this stage, a removable partial denture (RPD) was fabricated and delivered as a temporary rehabilitative solution to restore function and esthetics while maintaining arch integrity and preserving space for future definitive rehabilitation.
Following insertion of the RPD, the patient reported improved mastication and greater comfort during speech. Esthetic improvement was particularly evident in the anterior region, contributing positively to the patient’s self-confidence.
Clinical follow-up during the initial post-insertion period demonstrated good adaptation to the prosthesis, satisfactory retention and stable occlusal relationships. No signs of mucosal irritation or pressure-related discomfort were observed. The appliance effectively maintained arch space and supported occlusal stability.
Long-term management will involve a multidisciplinary approach, including orthodontic, surgical and prosthetic interventions. After completion of skeletal growth, definitive treatment may include surgical removal of supernumerary teeth, orthodontic traction and alignment of impacted teeth, maxillary expansion if indicated and implant-supported rehabilitation to achieve optimal functional and esthetic outcomes.
Regular follow-up appointments have been scheduled to monitor skeletal development, eruption patterns and prosthesis adaptation, ensuring a timely transition to definitive treatment.
Results and follow-up
A removable partial denture (RPD) was fabricated and delivered according to the treatment plan. Following placement, the patient reported improved mastication, greater comfort during speech and improved esthetic appearance, particularly in the anterior region.
Clinical evaluation demonstrated good adaptation of the prosthesis to the supporting tissues, satisfactory retention and stable occlusal relationships. No signs of mucosal irritation or pressure-related discomfort were observed during follow-up visits.
The RPD effectively preserved arch space and maintained occlusal stability, supporting future definitive treatment planning. Periodic follow-up appointments were scheduled to monitor skeletal growth, eruption patterns and prosthesis adaptation.
The clinical outcome following RPD placement is presented in Figs. 12 and 13.
Fig. 12.
Clinical photographs of the patient after insertion of the removable partial denture (RPD), demonstrating improved esthetics
Fig. 13.
Removable partial denture prior to insertion, illustrating prosthetic design and structure
Discussion
Cleidocranial dysplasia (CCD) is a rare skeletal disorder that may remain undiagnosed for extended periods, particularly when clinical findings are interpreted in isolation. In the present case, the patient had previously been classified as having growth delay despite normal endocrine evaluation. This reflects a common diagnostic challenge, as short stature and delayed development may overlap with endocrine or constitutional conditions.
The combination of skeletal and dental findings observed in this patient is consistent with previously reported cases of CCD. Hypoplastic clavicles, delayed cranial ossification and multiple impacted and supernumerary teeth represent the classical triad described in the literature [3, 6]. Previous reports have emphasized that dental abnormalities are often the most prominent clinical feature and may serve as the first indicator leading to diagnosis.
In line with existing evidence, prolonged retention of primary teeth and failure of eruption of permanent dentition in CCD are associated with altered bone remodeling and disturbed eruption mechanisms related to RUNX2 dysfunction [2, 7, 8]. The high number of impacted and supernumerary teeth observed in this case is consistent with findings described in both clinical and radiographic studies.
Radiographic imaging plays a central role in confirming the diagnosis and guiding treatment planning. While panoramic radiography provides an overview of eruption disturbances, CBCT offers detailed three-dimensional assessment of impacted teeth and their relationship to adjacent anatomical structures [9, 10]. Similar imaging approaches have been recommended to optimize treatment planning in complex CCD cases.
Management strategies for cleidocranial dysplasia are complex and should be individualized according to patient age, skeletal maturity, severity of dental impaction, craniofacial morphology, functional needs and patient-related factors [11, 12]. Several established protocols advocate early surgical exposure combined with orthodontic traction to guide eruption of impacted permanent teeth and improve occlusal development [11]. Such approaches may offer important advantages, including earlier orthodontic rehabilitation and improved eruption guidance. However, they may also require multiple surgical procedures, prolonged orthodontic treatment and a high level of patient compliance.
In the present case, early surgical exposure and orthodontic traction were carefully considered but were not selected as the initial treatment approach. The patient presented with extensive dental impaction, multiple supernumerary teeth, a high-arched narrow palate, ongoing skeletal development and immediate functional and esthetic concerns. Therefore, a conservative interim approach was selected to restore mastication, speech and esthetics while preserving arch space and allowing time for coordinated multidisciplinary planning.
The removable partial denture was not intended as definitive treatment, but as a temporary rehabilitative measure. Definitive treatment remains planned and may include surgical removal of supernumerary teeth, orthodontic traction of impacted teeth, maxillary expansion if indicated and implant-supported rehabilitation after completion of skeletal growth [11, 12]. This staged strategy was considered an appropriate risk-benefit approach for the present patient, as it addressed immediate functional and psychosocial needs while avoiding extensive intervention before final multidisciplinary planning.
Compared with previously reported cases, the present case highlights a similar pattern of delayed diagnosis and complex dental involvement, but also emphasizes the role of dental assessment in identifying CCD in patients initially evaluated for growth delay. The present report also demonstrates the importance of individualized treatment planning, as management decisions in CCD should be guided not only by chronological age but also by skeletal maturity, functional needs, patient-related factors and the extent of craniofacial involvement.
This case also highlights the importance of increased clinical awareness, particularly in regions where epidemiological data are limited. Early recognition of the characteristic dental and skeletal pattern of CCD can significantly reduce diagnostic delay and improve long-term treatment outcomes.
Limitations
This case report has several limitations. Molecular genetic testing for RUNX2 mutations was not performed due to limited availability of diagnostic resources. Although the diagnosis was strongly supported by the characteristic clinical and radiographic findings, the absence of genetic confirmation limits genotype-phenotype correlation and prevents molecular confirmation of the condition. In addition, genetic analysis could have provided further information regarding inheritance patterns and familial screening. Additionally, long-term follow-up data are limited, and future outcomes following definitive surgical and orthodontic treatment remain to be evaluated.
Conclusion
This case illustrates the diagnostic complexity of cleidocranial dysplasia and highlights the important role of dental assessment in recognizing the condition. Persistent failure of tooth eruption combined with characteristic skeletal findings should raise suspicion of an underlying systemic disorder.
Early and accurate diagnosis enables a structured, stage-based management approach tailored to skeletal maturity. In this patient, postponing invasive intervention and implementing a conservative interim prosthetic strategy allowed functional rehabilitation while preserving conditions for future definitive treatment.
From a clinical perspective, this case underscores the importance of interdisciplinary collaboration and careful treatment timing. Aligning therapeutic interventions with skeletal development is essential to optimize functional and esthetic outcomes while minimizing treatment-related risks. Clinicians should consider CCD in patients presenting with delayed tooth eruption and unexplained growth abnormalities, as early recognition and appropriate referral can significantly improve long-term outcomes.
CARE guidelines
The manuscript has been revised in accordance with the CARE reporting guidelines.
Authors' contributions
E.Ç. performed the clinical diagnosis, evaluated the patient and was responsible for the overall clinical management and treatment planning. E.Ç. coordinated the case, contributed to clinical interpretation and prepared the manuscript. A.R. assisted with clinical documentation. All authors read and approved the final manuscript.
Funding
The authors received no financial support for this study.
Data availability
All data generated or analyzed during this study are included in this published article. Additional clinical data are available from the corresponding author upon reasonable request, in accordance with patient confidentiality.
Declarations
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the University Clinical Center of Kosovo (Approval No. 230/2, dated 24 March 2025). The study was conducted in accordance with the principles of the Declaration of Helsinki.
Consent for publication
Written informed consent for publication of this case report, including clinical data and diagnostic images, was obtained from the patient’s parent/legal guardian. The parent was fully informed about the purpose of the publication and the type of data to be used. All patient information has been handled in accordance with ethical standards and personal identifiers have been removed to ensure confidentiality. A copy of the written consent is available for review by the Editor of this journal upon request. All patient data were anonymized and no identifying information is included.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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References
- 1.Orphanet. Cleidocranial dysplasia. Paris: INSERM. 2026. Available from: https://www.orpha.net
- 2.Mundlos S. Cleidocranial dysplasia: clinical and molecular genetics. J Med Genet. 1999;36(3):177–82. [PMC free article] [PubMed] [Google Scholar]
- 3.Jaruga A, Hordyjewska E, Kandzierski G, Tylzanowski P. Cleidocranial dysplasia and RUNX2: clinical phenotype–genotype correlation. Clin Genet. 2016;90(5):393–402. [DOI] [PubMed] [Google Scholar]
- 4.Cooper SC, Flaitz CM, Johnston DA, Lee B, Hecht JT. A natural history of cleidocranial dysplasia. Am J Med Genet. 2001;104(1):1–6. [DOI] [PubMed] [Google Scholar]
- 5.Golan I, Baumert U, Hrala BP, Müßig D. Cleidocranial dysplasia: review and a case report. Quintessence Int. 2003;34(8):607–14. [Google Scholar]
- 6.Dhanrajani PJ. Dental manifestations of cleidocranial dysplasia: a case report. J Indian Soc Pedod Prev Dent. 2002;20(4):155–60. [Google Scholar]
- 7.Li Y, Wang J, Zhang H, et al. Clinical and genetic analysis of cleidocranial dysplasia: expanding the RUNX2 mutation spectrum. Front Genet. 2021;12:748111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Cheng A, Wang Y, Li J, et al. Genotype–phenotype correlation in cleidocranial dysplasia: a systematic review. Orphanet J Rare Dis. 2022;17(1):134. [Google Scholar]
- 9.Tanaka JL, Ono E, Filho EM, Castilho JC, Moraes LC, Moraes ME. Cleidocranial dysplasia: importance of radiographic images in diagnosis of the condition. J Oral Sci. 2006;48(3):161–6. [DOI] [PubMed] [Google Scholar]
- 10.Patil S, Maheshwari S, Khandelwal S. Role of cone-beam computed tomography in diagnosis and management of impacted teeth in cleidocranial dysplasia. Imaging Sci Dent. 2021;51(2):185–92. [Google Scholar]
- 11.Jensen BL, Kreiborg S. Dental treatment strategies in cleidocranial dysplasia. Br Dent J. 1992;172(6):243–7. [DOI] [PubMed] [Google Scholar]
- 12.Zhang CY, Si Y, Wang XZ, Sun XY, Yan WJ, Zheng SG. Early dental treatments for patients with cleidocranial dysplasia. Chin J Dent Res. 2015;18(1):51–7. [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this published article. Additional clinical data are available from the corresponding author upon reasonable request, in accordance with patient confidentiality.