[Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia].

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia / 中华口腔医学杂志

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

Cleidocranial dysostosis: a case report with clinical illustration.

Cleidocranial Dysostosis or Dysplasia (CCD) is an infrequent clinical condition, with an autosomal dominant hereditary mode of inheritance. Triad lesions: multiple supernumerary teeth, partial or complete absence of the clavicles and open sagittal sutures and fontanelles. Nine-year-old female patient comes to our service for outpatient consultation with the main complaint of upper limbs mobility restriction with shoulders hypermotility. The chest X-ray showed partial absence of the clavicles and a cone-shaped thorax. The diagnosis of CCD was performed. Treatment of these patients requires a multidisciplinary approach which includes orthopaedic and dental corrections. The premature diagnosis allows a proper orientation for the treatment, offering a better life quality for the patient.

Disostosis cleidocraneal a tres años de tratamiento ortopédico / Cleidocraneal dysostosis at three years of orthopedic treatment

Introducción: La disostosis cleidocraneal es un trastorno genético raro con patrón hereditario. Sus rasgos patognomónicos son la aplasia clavicular, fontanelas y suturas abiertas, múltiples anomalías dentales. Su origen se relaciona con alteraciones en el gen RUNX2, importante para la síntesis de CBFA1, que a su vez funciona como un conformador óseo y un diferenciador de osteoblastos. Caso clínico: Paciente de 11 años con características clínicas de CCD, se corroboran los antecedentes genéticos hereditarios y alteraciones dentales relacionados con disostosis cleidocraneal. Resultado: A tres años de tratamiento se observa mejor definición facial, la erupción de piezas permanentes retenidas y mejor función masticatoria. Conclusión: Mejorar la calidad de vida del paciente con tratamientos interceptivos y el conocimiento de las alteraciones causadas por el síndrome, así como el trabajo interdisciplinario (AU)

Introduction: Cleidocranial dysostosis is a rare genetic disorder with a hereditary pattern. Its pathognomonic features are clavicular aplasia, fontanelles and open sutures, multiple dental anomalies. Its origin is related to alterations in the RUNX2 gene, important for the synthesis of CBFA1, which in turn functions as a bone conformer and an osteoblast differentiator. Clinical case: Patient with eleven years old with clinical characteristics of CCD, hereditary genetic background, and dental alterations related to cleidocranial dysostosis are corroborated. Result: After three years of treatment, the facial definition is better, the eruption of permanent pieces retained and better chewing function. Conclusion: Improve the quality of life of the patient with interceptive treatments and the knowledge of the alterations caused by the syndrome, as well as the interdisciplinary work (AU)

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

BACKGROUND: Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. METHODS: Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. RESULTS: Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. CONCLUSIONS: Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

Cleidocranial Dysplasia: A Review of Clinical, Radiological, Genetic Implications and a Guidelines Proposal.

In this review, we aimed to depict the clinical, radiological, and genetic features of cleidocranial dysplasia (CCD) and to suggest management guidelines, based on our experience of 8 cases, with an emphasis given to dental complications.The most common craniofacial features of CCD that stand out are a patency of the anterior fontanelle, an inverted pear-shaped calvaria, a hypertelorism, a general midface retrusion, and a mandible prognathism, associated with an excessive mobility of the shoulders, a short stature, and teeth abnormalities such as supernumerary teeth and failure of eruption, in particular. RUNX2 is the only gene in which mutation is known to cause CCD, but mutations are detected in only 65% of all patients with a clinical diagnosis of CCD. Panoramic radiography is a valuable adjunct in confirming the diagnosis of CCD.Our experience allowed us to conclude that orthodontically aided eruption should always be attempted. However, to stabilize the occlusion and to improve facial esthetics, we recommend associated orthognathic surgery. When orthodontic treatment is partially efficient, prosthetic treatment options bring satisfactory results, in terms of occlusion. Nevertheless, when orthodontic treatment fails, we recommend to preserve as many native teeth as possible, and to combine orthognathic preprosthetic surgery and implant-supported prosthesis.In any case, an individualized treatment protocol, depending on the needs and demand of the patient, the age at diagnosis and social and economic circumstances, should be put forward.

Restorative treatment strategies for patients with cleidocranial dysplasia.

OBJECTIVE: To develop a suitable treatment strategy for patients with cleidocranial dysplasia (CCD) who miss the optimal early treatment stage. MATERIALS AND METHODS: This study enrolled 15 patients with CCD who had all missed the optimal treatment stage and were diagnosed with CCD through clinical examinations and genetic tests. Based on the chief complaints and requirements of the patients, three different therapeutic schedules were devised for these patients. Schedules I (periodontal and endodontic treatments) and II (periodontal, endodontic and prosthodontic treatments) were used for patients with low requirements, whereas Schedule III (multidisciplinary strategy, including periodontal, endodontic, surgical, orthodontic and prosthodontic treatments) was used for patients with high requirements. RESULTS: Schedules I, II and III were used in five, seven and three patients, respectively. Schedule III treatments produced the best outcomes in terms of occlusion and esthetics. CONCLUSIONS: Schedule III based on a comprehensive multidisciplinary therapy is an ideal restorative therapeutic strategy and can achieve good outcomes for patients with CCD who missed the optimal treatment stage.

Advantages of cone beam computed tomography (CBCT) in the orthodontic treatment planning of cleidocranial dysplasia patients: a case report.

Our aim was to discuss, by presenting a case, the possibilities connected to the use of a CBCT exam in the dental evaluation of patients with Cleidocranial Dysplasia (CCD), an autosomal dominant skeletal dysplasia with delayed exfoliation of deciduous and eruption of permanent teeth and multiple supernumeraries, often impacted. We think that CBCT in this patient was adequate to accurately evaluate impacted teeth position and anatomy, resulting thus useful both in the diagnostic process and in the treatment planning, with an important reduction in the radiation dose absorbed by the patient.

Diagnóstico y tratamiento de dientes retenidos: comunicación de 2 casos con disostosis cleido-craneo-facial / Diagnosis and treatment of impacted teeth: report of 2 cases with cleidocranial dysplasia

La disostosis cleidocraneal es una enfermedad esqueletal rara que se caracteriza por retardo en la osificación cranel, hipoplaisa o aplasia clavicular y anomalías dentarias. En esta publicación se mostrarán dos casos en que se involucra la genética y las enfermedades del sistema óseo y dentario, corresopndientes a dos miembros de la misma familia. Se detallan la etiología y patogenia, así como los hallazgos clínicos y radiográficos.

Cleidocranial dysplasia: diagnostic criteria and combined treatment.

Cleidocranial dysplasia (CCD) is an uncommon, generalized skeletal disorder characterized by delayed ossification of the skull, aplastic or hypoplastic clavicles, and serious, complex dental abnormalities. There are many difficulties in the early diagnosis of CCD because a majority of the craniofacial abnormalities becomes obvious only during adolescence. In the present case, a hypoplastic midface, a relative prognathia of the mandible, and close approximation of the shoulders in the anterior plane were the conspicuous extraoral findings. Prolonged exfoliation of the primary dentition, unerupted supernumerary teeth, and the irregularly and partially erupted secondary dentition produced occlusional anomalies. The presence of the second permanent molars together with the primary dentition and wide spacing in the lower incisor area were typical dental signs. Gradual extraction of the supernumerary teeth and over-retained primary teeth was the first step of oral surgery. This was followed by a surgical exposure of the unerupted teeth by thinning of the cortical bone. Orthodontic treatment was aimed at parallel growth of the jaws. Removable appliances were used to expand the narrow maxillary and mandibular arches, and a Delaire mask compensated for the lack of sagittal growth of the upper jaw. Temporary functional rehabilitation was solved by partial denture. When the jaws have been fully developed, implant insertions and bridges are the therapeutic measures. The reported case and the literature data support the importance of the early diagnosis and interdisciplinary treatment of CCD.

Displasia cleidocraniana: relato de caso clínico / Cleidocranial dysplasi: case report

Paciente de 24 anos, sexo feminino, portadora de sinais característicos da Displasia Cleidocraniana foi submetida a exames clínico e radiográfico, os quais evidenciaram anormalidades na aparência física e constituição esquelética da mesma, confirmando a suspeita diagnóstica. O tratamento proposto foi excisão cirúrgica de numerosos dentes inclusos, para viabilizar posterior reabilitação protética. A peça cirúrgica foi encaminhada para exame histopatológico, para avaliar a presença de lesão cística e possíveis distúrbios na constituição morfológica dos dentes removidos. Diante da raridade desta síndrome, este artigo objetiva relatar os aspectos gerais da doença e a terapêutica utilizada

Cleidocranial dysplasia: Part 2--Treatment protocol for the orthodontic and surgical modality.

The principles on which the present approach to the treatment of cleidocranial dysplasia are based were stated in part 1 of this article. Comparison was made with two other methods and the advantages of the present method were described in terms of (a) how this method is adapted to the clinical features of the condition, (b) when surgical intervention is appropriate, (c) how the dynamic appliance system may be adapted to the changing environment as more teeth erupt, and (d) the importance of rapidly bringing about the eruption of the anterior teeth. The practical aspects of the treatment are now described step-by-step with illustrations taken from the treatment of several different patients.

Cleidocranial dysplasia: Part 1--General principles of the orthodontic and surgical treatment modality.

Over several decades, occasional reports of dental treatment provided by an individual practitioner to patients suffering with cleidocranial dysplasia have appeared in the literature. In the past, the main treatment was prosthetic replacement. Orthodontic treatment has only recently been considered as a serious treatment option, with success being described in several aspects of this treatment modality, in published individual case reports. Given the rarity of the condition, guidelines for the treatment of cleidocranial dysplasia are difficult to find in the literature, because few practitioners have treated enough cases to be in a position to make such recommendations. Two different approaches have been proposed in the past and are discussed here. The relative advantages of a third approach are expounded in detail.

[Cleidocranial dysplasia: review of the literature and presentation of a case]. / La dysplasie cléidocrânienne: mise à jour et présentation d'un cas.

Cleidocranial Dysplasia, although not frequent, can present to the dentist. In this article, we have reviewed the literature concerning this disease and we present a patient with this condition. An overview of the disease would reveal partial to complete absence of clavicles, delayed closing of cranial fontanels, prolonged retention of deciduous teeth, subsequent delay in eruption of permanent teeth and multiple impactions.

Disostose cleido cranial: relato de um caso clínico / Cleidocranial dysostosis: report of a case

Os autores apresentam um caso de disostose cleido cranial em paciente jovem. A ênfase ao diagnóstico e tratamento precoce da doença, assim como o acompanhamento do caso, ensejará um tratamento odontológico e ortopédico adequado, e aconselhamento genético

Dental treatment strategies in cleidocranial dysplasia.

Based on the findings of our recent longitudinal study on the abnormalities of the dentition in cleidocranial dysplasia (CCD), a hypothesis has been proposed, which makes it possible to predict time of onset of formation of supernumerary teeth and their location in the jaws. It was found that a diagnosis should be made early so that formation of supernumerary teeth can be diagnosed and early intervention undertaken. It should be possible to diagnose supernumerary incisors at about 5-7 years of age and supernumerary canines and premolars a few years later. When root length of the normal permanent teeth has reached about one third of its final length, the overlying supernumerary teeth should be removed, together with overlying bone and primary teeth. In regions where no supernumerary teeth are formed, eruption may also be improved by removal of the primary teeth and surgical exposure of the underlying permanent teeth. Conventional orthodontic treatment and eventually autotransplantation of teeth may still be necessary in the future, but it can be anticipated that the new strategy, with much earlier intervention, will materially reduce the extent of surgical and orthodontic interventions, which have previously been of extremely long duration, tedious to the patients and often of limited success.

[Therapeutic approaches for patients with cleidocranial dysostosis]. / Behandlungsmassnahmen bei Patienten mit Dysostosis cleidocranialis.

In three cases of c.c.d. it could be shown, that combined orthodontic and surgical treatment provided further possibilities for the treatment of severe problems in permanent dentitions as well as correcting extreme skeletal discrepancies of the facial skeleton in c.c.d. Well-scheduled removal of supernumerary teeth creates space for the spontaneous eruption of delayed teeth. By the use of carefully applied orthodontic forces, alignment of even extremely displaced teeth is shown to be possible. Furthermore, it is demonstrated that careful planning and realization of osteotomies in the midface can remarkably improve the facial appearance and the relationship of the jaws thus facilitating particularly future prosthodontic treatment.