Three-dimensional evaluation of dental characteristics in patients with Cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption. METHODS: Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed. RESULTS: The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number. CONCLUSIONS: This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.

Restoration of a Maxillary Anterior Defect With a Rotational Path Removable Partial Denture: Clinical Report of a Patient With Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an uncommon genetic condition that affects teeth and bones, potentially leading to delayed ossification, dental abnormalities, and craniofacial changes, which can be treated through a combination of orthodontic and prosthodontic therapies. This case report describes the diagnostic evaluation, laboratory procedures, and prosthodontic treatment for a patient with CCD who had two missing maxillary anterior teeth. Following occlusal device therapy and the achievement of occlusal equilibration, restorative treatment was performed, consisting of a maxillary central incisor survey crown, rest seat preparations, and a lateral rotational path removable partial denture (RPD). The article highlights the value of this type of RPD as an alternative restoration for the replacement of missing anterior teeth.

[Analysis of clinical phenotypes and genetic variants in two children with sporadic cleidocranial dysplasia].

OBJECTIVE: To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia. METHODS: The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. RESULTS: The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. CONCLUSION: For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.

Suspected Endodontic Failure in a Patient with Cleidocranial Dysplasia: A Case Report.

A patient's medical history and related dental manifestations can significantly contribute to confounding signs and symptoms leading to a diagnostic challenge. An 18-year-old female patient presented with persistent radiographic radiolucency associated with the apex of a previously treated tooth (tooth 9); asymptomatic apical periodontitis and endodontic failure were suspected. This report presents how a patient's condition of cleidocranial dysplasia had a profound effect on her dental history, which included the presence of multiple supernumerary teeth. Extensive surgical intervention during the patient's childhood was required to remove the supernumerary teeth, which resulted in an endodontic misdiagnosis in her adult life. After clinical and radiographic examination, the patient was diagnosed with a periapical scar. Periapical fibrous scars have a prevalence of between 2.5% and 12% and are a rare healing process with fibrous tissue after surgical and nonsurgical interventions. This report describes the diagnosis and pathophysiology of fibrous scars, including their risk factors and long-term monitoring approaches.

Multidisciplinary prosthetic rehabilitation of an adult patient with cleidocranial dysplasia by using a rapid external distraction device: A clinical report.

The multidisciplinary treatment of a 41-year-old man with cleidocranial dysplasia is described. A rapid external distraction device was used to reposition the maxilla before the prosthodontic rehabilitation.

RUNX2 Nonsense Mutation Associated with Cleidocranial Dysplasia with Unusual Dental Features.

Purpose: The purpose of this case report is to describe a RUNX2 nonsense mutation associated with cleidocranial dysplasia (CCD) with unusual dental features. The patient was a 12-year-old Brazilian girl who sought dental care due to over-retention of primary teeth and absence of erupted permanent teeth. Clinical and radiographic examinations revealed multiple impacted permanent teeth, a prominent cingulum of the permanent impacted maxillary incisors and enamel defects (hypoplasia and hypomineralization) in addition to skeletal abnormalities. No supernumerary teeth were present. The diagnostic hypothesis of CCD was raised and the patient was refer- red to the genetic medical service, where the diagnosis was cofirmed. After RUNX2 genetic screening, including polymerase chain reaction and sequencing of both DNA strands, a heterozygous nonsense mutation was identified in exon 2 (c.193 C>T [Q65X]). This article reports unusual dental features in a patient with CCD.

An overview of the intraoral features and craniofacial morphology of growing and adult Japanese cleidocranial dysplasia subjects.

BACKGROUND: Orthodontic treatment for cleidocranial dysplasia (CCD) requires an understanding of the nature of the retained deciduous teeth, supernumerary teeth, delayed eruption of the permanent teeth, and craniofacial morphology from childhood to adulthood. This study aimed to provide an overview of the intraoral and craniofacial characteristics of growing and adult Japanese CCD subjects. METHODS: We assessed cross-sectionally the intraoral features of 28 CCD subjects (males, 15.3 ± 7.0 years; females, 15.2 ± 5.1 years) using orthopantomograms and photographs. Mean facial diagrams (profilograms) of 3 age groups (5-10 years, 11-14 years, over 15 years: adult) were constructed, and linear and angular measurements of 2 age groups (under 15 years, adult) were performed by using cephalograms. The data were compared with Japanese standards. RESULTS: A mean of 11.7 and 8.4 retained deciduous teeth, 10.4 and 15.8 erupted permanent teeth were observed in the adult males and females, and a mean of 6.8 and 5.3 supernumerary teeth were observed in all males and females, respectively. A positive correlation was found between the number of supernumerary teeth and the age at initial visit. Cephalometric analysis showed an average to anteriorly positioned maxilla, a tendency for counter-clockwise rotation of the ramus, and a prognathic mandible in all groups. CONCLUSIONS: The number of supernumerary teeth increased with age. The maxilla was average to anteriorly positioned, and the mandible was counter-clockwise rotated and prognathic for all groups. These characteristic craniofacial morphologies and changes of intraoral conditions at different ages in CCD patients should be considered when proposing rational orthodontic treatment plans.

Cleidocranial dysplasia and novel RUNX2 variants: dental, craniofacial, and osseous manifestations.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a skeletal disorder affecting cranial sutures, teeth, and clavicles, and is associated with the RUNX2 mutations. Although numerous patients have been described, a direct genotype-phenotype correlation for RUNX2 has been difficult to establish. Further cases must be studied to understand the clinical and genetic spectra of CCD. To characterize detailed phenotypes and identify variants causing CCD in five unrelated patients and their family members. METHODOLOGY: Clinical and radiographic examinations were performed. Genetic variants were identified by exome and Sanger sequencing, data were analyzed by bioinformatics tools. RESULTS: Three cases were sporadic and two were familial. Exome sequencing successfully detected the heterozygous pathogenic RUNX2 variants in all affected individuals. Three were novel, comprising a frameshift c.739delA (p.(Ser247Valfs*)) in exon 6 (Patient-1), a nonsense c.901C>T (p.(Gln301*)) in exon 7 (Patient-2 and affected mother), and a nonsense c.1081C>T (p.(Gln361*)) in exon 8 (Patient-3). Two previously reported variants were missense: the c.673C>T (p.(Arg225Trp)) (Patient-4) and c.674G>A (p.(Arg225Gln)) (Patient-5) in exon 5 within the Runt homology domain. Patient-1, Patient-2, and Patient-4 with permanent dentition had thirty, nineteen, and twenty unerupted teeth, respectively; whereas Patient-3 and Patient-5, with deciduous dentition, had normally developed teeth. All patients exhibited typical CCD features, but the following uncommon/unreported phenotypes were observed: left fourth ray brachymetatarsia (Patient-1), normal clavicles (Patient-2 and affected mother), phalangeal malformations (Patient-3), and normal primary dentition (Patient-3, Patient-5). CONCLUSIONS: The study shows that exome sequencing is effective to detect mutation across ethnics. The two p.Arg225 variants confirm that the Runt homology domain is vital for RUNX2 function. Here, we report a new CCD feature, unilateral brachymetatarsia, and three novel truncating variants, expanding the phenotypic and genotypic spectra of RUNX2 , as well as show that the CCD patients can have normal deciduous teeth, but must be monitored for permanent teeth anomalies.

Clinical, radiographic, and genetic observations in 2 families with cleidocranial dysplasia.

The clinical, radiographic, and molecular alterations in 7 individuals belonging to 2 families with clinical characteristics of cleidocranial dysplasia (CCD) were investigated. The patients underwent karyotype and genetic sequencing examinations. Cytogenetic analysis did not demonstrate any alterations. The next-generation sequencing technique employed for the molecular analysis revealed sequence variations in the RUNX2 gene: c.568C>T (p.Arg190Trp) in exon 4 in family A and c.1205del (p.Pro402Argfs*82) in exon 9 in family B. Incomplete closure of anterior fontanels, hypoplastic clavicles, and dental changes were observed in all 7 patients. Uncommon clinical findings, such as partial hearing loss and bilateral clavicular agenesis, were noted in some patients. According to the literature consulted, this is the first time that the total absence of the pubic bone in a study subject is being reported. The variable expression among individuals of the same family and between families A and B suggests the absence of a genotype-phenotype relationship. Early diagnosis allows the dentist to minimize the effects of changes associated with CCD by monitoring and providing appropriate treatment, and the identification of genetic sequence variations enables appropriate family genetic counseling.

Appropriateness of standard cephalometric norms for the assessment of dentofacial characteristics in patients with cleidocranial dysplasia.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a rare skeletal syndrome affecting craniofacial and dental development. As a consequence, conventional cephalometric landmarks may not be valid for CCD patients, and the appropriateness of norms used for the general population should be critically discussed. METHODS: Five patients 9- to 22-year-old (three females, two males) with CCD were included. Lateral-cephalograms, orthopantomographies, and intra-oral photos were retrospectively analysed. Lateral-cephalograms of 50 normal controls (ten for each CCD patient) matched for age and sex were selected from an online database. Cephalometric measurements of each CCD patients were compared with average values of matched controls using Wilcoxon signed-rank test for paired values (α = 0.05). RESULTS: In CCD patients, a shortening of the cranial base was present (ΔSN = -17.1 mm, p = 0.043). Thus, the mandible (ΔSNPg = +9.5°, p = 0.043) and the maxilla (ΔSNA = +11.2°, p = 0.043) showed protrusion compared to the cranial base, despite a reduced maxillary (ΔCo-A = -15.1 mm, p = 0.043) and mandibular (ΔCo-Gn = -15.2 mm, p = 0.080) length. The mandibular divergence was reduced (ΔSN/GoGn = -6.4°, p = 0.043), a reduced overbite was present (ΔOverbite = -2.9 mm, p = 0.043), and the interincisal angle was increased (ΔInterincisalAngle = +13.7°, p = 0.043), mainly due to retro-inclination of lower incisors. CONCLUSIONS: Standard cephalometric norms for the assessment of horizontal jaw position may not be applicable to CCD patients because of a reduced anterior cranial base length compared to normal subjects. Vertical relationships may not be affected, and mandibular hypodivergency was confirmed.

Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon.

Hypophosphatasia (HPT) and cleidocranial dysplasia (CCD) are rare genetic disorders characterized by both defective ossification and bone mineralization. Patients usually present with craniosynostosis and cranial defects which in many cases require surgical repair. There is only 1 reported case of combined HPT and CCD in the literature. Our reported case involves a 3.5-year-old girl with concomitant homozygous CCD and heterozygous HPT. The child had an extended cranial defect since birth which improved with the administration of Strensiq and was followed until preschool age. Bone defects were relatively minor on revaluation. Due to the limited final defect, we decided not to intervene. In HPT-CCD patients, bone defects are overestimated due to osteomalacia, and thus, management strategy should be less aggressive. They should undergo surgical repair with cranioplasty with the use of cement and/or titanium meshes in case of extended final defects.

Congenital Pseudarthrosis of the Tibia Associated With Cleidocranial Dysostosis: Case Report and Literature Review.

CASE: We describe a case of 2 individually rare diseases existing comorbidly in the form of congenital pseudarthrosis of the tibia (CPT) coincident with cleidocranial dysostosis and provide a review of the literature, including the sole preexisting documented coincidence. CONCLUSION: Understanding, treatment, and surgical protocol of CPT have changed considerably since this comorbidity was last reported. Updates include synostosis, periosteal grafting, the use of bone morphogenetic protein, and bisphosphonates. Our case varies from the previous in associated disorder and family history. The relationship between CBFA1 and RUNX2 genes may hold the key, but further study is needed.

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.

Identification of a Novel Splice Site Mutation in RUNX2 Gene in a Family with Rare Autosomal Dominant Cleidocranial Dysplasia.

Background: Pathogenic variants of RUNX2, a gene that encodes an osteoblast-specific transcription factor, have been shown as the cause of Cleidocranial dysplasia (CCD), which is a rare hereditary skeletal and dental disorder with dominant mode of inheritance and a broad range of clinical variability. Due to the relative lack of clinical complications resulting in CCD, the medical diagnosis of this disorder is challenging, which leaves it underdiagnosed. Methods: : In this study, nine healthy and affected members of an Iranian family were investigated. PCR and sequencing of all exons and exon-intron boundaries of runt-related transcription factor 2 (RUNX2; NM_001024630) gene was performed on proband. Co-segregation analysis was conducted in the other family members for the identified variant. Additionally, a cohort of 100 Iranian ethnicity-matched healthy controls was screened by Amplification Refractory Mutation System PCR method. Results: The novel splice site variant (c.860-2A>G), which was identified in the intron 6 of RUNX2 gene, co-segregated with the disease in the family, and it was absent in healthy controls. Pathogenicity of this variant was determined by several software, including , human splicing finder, which predicts the formation or disruption of splice donor sites, splice acceptor sites, exonic splicing silencer sites, and exonic splicing enhancer sites. In silico analysis predicted this novel variant to be disease causing. Conclusion: The identified variant is predicted to have an effect on splicing, which leads to exon skipping and producing a truncated protein via introducing a premature stop codon.

Imaging studies used as aid in the diagnosis of cleidocranial dysplasia. A review / Estudios de imagen utilizados como ayuda en el diagnóstico de displasia cleidocraneal. Una revisión

Cleidocranial dysplasia (CCD), also known as Marie-Sainton syndrome, is a rare disorder of autosomal dominant type that presents specific characteristics at the skeletal and dental level. The diagnosis of CCD is based on clinical and radiographic findings. Panoramic, cephalometric and anterior poster radiographs have been used for its diagnosis in dentistry. However, these radiological techniques have limitations, and advances in technology with new imaging studies such as magnetic resonance imaging (MRI) and ultrasound have emerged, contributing to the diagnosis of CCD. Therefore, the aim of this review was to identify and describe current imaging studies that contribute to both the diagnosis and adequate and efficient treatment planning of CCD, and describe the clinical and radiographic characteristics of patients with this syndrome. (AU)

La displasia cleidocraneal (DCC), también conocida como síndrome de Marie-Sainton, es un trastorno poco común de tipo autosómico dominante, que presenta características específicas a nivel esquelético y dental. El diagnóstico de DCC se basa en hallazgos clínicos y radiográficos. Las radiografías panorámicas, cefalométricas y posteroanteriores se han utilizado para su diagnóstico en el área de la odontología, pero con los avances de la tecnología y debido a las limitaciones de estas técnicas radiológicas han surgido nuevos estudios de imagen como la resonancia magnética (RM) y la ecografía, que contribuyen al diagnóstico de DCC. Por lo tanto, el propósito de esta revisión fue identificar y describir los estudios de imagen actuales que aportan tanto al diagnóstico como a la planificación del tratamiento adecuado y eficiente de la DCC, y permiten describir las características clínicas y radiográficas de los pacientes con este síndrome. (AU)

Prosthetic rehabilitation of a patient with cleidocranial dysplasia using dental implants-a clinical report.

Adult patients with oral manifestations of untreated syndromic malformations usually exhibit a high degree of suffering. In this clinical report, we describe the implant-supported prosthetic treatment of a patient with cleidocranial dysplasia, a rare autosomal-dominant inherited malformation syndrome. Therapy for oral manifestations of cleidocranial dysplasia should be started in early childhood; however, the 26-year-old patient in the present study had not undergone orthodontic therapy in childhood. The treatment measures performed prior to this study were limited to the removal of several permanent teeth. Surgical pretreatment, placement of six implants each in the maxilla and mandible, and prosthetic restoration are described. The implantation was guided using a three-dimensional template. Long-term immediate temporary restoration and immediate loading of the implants were performed. The definitive prosthetic restoration was completed using fixed, acrylic resin-veneered screw-retained fixed dental prostheses. The clinical and radiological parameters observed in this case suggest that surgical and prosthetic procedure concepts from implantology can be adopted for patients with CCD.

Nuss procedure for pectus excavatum in a patient with cleidocranial dysplasia.

Cleidocranial dysplasia is an autosomal skeletal disorder resulting from delayed or abnormal ossification of bony growth. Pectus excavatum independently presented in a 9-year-old boy with cleidocranial dysplasia and was corrected using the Nuss procedure. There were no perioperative complications, and the post-operative course was uneventful. Although there were concerns regarding extraordinary late consolidation or remodeling of the bony thorax, placement of a Nuss plate for 5 years and 6 months improved the patient's concave deformity without re-depression.