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Clinical Oral Investigations Oct 2023Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth...
OBJECTIVE
Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth characteristics of four patients with different SDs.
MATERIAL AND METHODS
Four SD patients with molecularly confirmed diagnoses, Pt-1 acromicric dysplasia, Pt-2 hypophosphatasia and hypochondroplasia, Pt-3 cleidocranial dysplasia, and Pt-4 achondroplasia, were recruited. A tooth from each patient was evaluated for mineral density (micro-computerized tomography), surface roughness (surface profilometer), microhardness, mineral contents (energy-dispersive X-ray), and ultrastructure (scanning electron microscopy and histology), and compared with three tooth-type matched controls.
RESULTS
Pt-1 and Pt-3 had several unerupted teeth. Pt-2 had an intact-root-exfoliated tooth at 2 years old. The lingual surfaces of the patients' teeth were significantly smoother, while their buccal surfaces were rougher, than controls, except for Pt-1's buccal surface. The patients' teeth exhibited deep grooves around the enamel prisms and rough intertubular dentin. Pt-3 demonstrated a flat dentinoenamel junction and Pt-2 had an enlarged pulp, barely detectable cementum layer, and ill-defined cemento-dentinal junction. Reduced microhardnesses in enamel, dentin, and both layers were observed in Pt-3, Pt-4, and Pt-1, respectively. Pt-1 showed reduced Ca/P ratio in dentin, while both enamel and dentin of Pt-2 and Pt-3 showed reduced Ca/P ratio.
CONCLUSION
Each SD has distinctive dental characteristics with changes in surface roughness, ultrastructure, and mineral composition of dental hard tissues.
CLINICAL RELEVANCE
In this era of precision dentistry, identifying the specific potential dental problems for each patient with SD would help personalize dental management guidelines.
PubMed: 37548766
DOI: 10.1007/s00784-023-05194-w -
International Journal of Surgery Case... 2019Cleidocranial dysplasia (CCD) is a rare congenital disease characterised by generalised skeletal and orofacial defects. The dental rehabilitation of patients with CCD is...
INTRODUCTION
Cleidocranial dysplasia (CCD) is a rare congenital disease characterised by generalised skeletal and orofacial defects. The dental rehabilitation of patients with CCD is a case-sensitive procedure requiring a multidisciplinary approach.
PRESENTATION OF CASE
A 24-year-old woman presented with the skeletal and oral manifestations of CCD, including multiple poorly erupted and impacted teeth. The patient was very depressed and rejected orthodontic treatment; therefore, we formulated a treatment plan involving extraction of all impacted and poorly erupted teeth under general anaesthesia, followed by fabrication and delivery of transitional complete dentures for cosmetic, functional, and psychological benefits. Three months later, 14 screw basal implants were inserted in the maxillary and mandibular jaws and subjected to immediate loading with fixed prostheses 3 days later. At the 3-year follow-up visit, the patient expressed satisfaction with the aesthetic and functional aspects of the prostheses and presented with excellent oral health.
DISCUSSION
The timing of diagnosis, patient's age, willingness to undergo the planned treatment, and treatment duration are valuable considerations for establishing an appropriate treatment plan for the oral manifestations of CCD.
CONCLUSION
To our knowledge, this is the first report on basal implant-based full-mouth rehabilitation in a patient with CCD. Basal implant-supported prostheses may be useful for patients with CCD who present with a limited bony foundation after tooth removal. The treatment requires lesser time than orthodontic treatment, eliminates the need for bone grafting, spares the patient from ill-fitting dentures, reduces the overall cost, and improves the quality of life.
PubMed: 31770711
DOI: 10.1016/j.ijscr.2019.11.005 -
American Journal of Medical Genetics.... Nov 2013Dental anomalies are common congenital malformations that can occur either as isolated findings or as part of a syndrome. This review focuses on genetic causes of... (Review)
Review
Dental anomalies are common congenital malformations that can occur either as isolated findings or as part of a syndrome. This review focuses on genetic causes of abnormal tooth development and the implications of these abnormalities for clinical care. As an introduction, we describe general insights into the genetics of tooth development obtained from mouse and zebrafish models. This is followed by a discussion of isolated as well as syndromic tooth agenesis, including Van der Woude syndrome (VWS), ectodermal dysplasias (EDs), oral-facial-digital (OFD) syndrome type I, Rieger syndrome, holoprosencephaly, and tooth anomalies associated with cleft lip and palate. Next, we review delayed formation and eruption of teeth, as well as abnormalities in tooth size, shape, and form. Finally, isolated and syndromic causes of supernumerary teeth are considered, including cleidocranial dysplasia and Gardner syndrome.
Topics: Abnormalities, Multiple; Animals; Anterior Eye Segment; Cleft Lip; Cleft Palate; Cysts; Dentition; Developmental Disabilities; Ectodermal Dysplasia; Eye Abnormalities; Eye Diseases, Hereditary; Holoprosencephaly; Humans; Lip; Mice; Orofaciodigital Syndromes; Tooth
PubMed: 24124058
DOI: 10.1002/ajmg.c.31382 -
Journal of Pharmacy & Bioallied Sciences Aug 2015Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition with generalized dysplasia of bone characterized by delayed closure of cranial sutures, hypoplastic... (Review)
Review
Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition with generalized dysplasia of bone characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We report two cases presenting with classical features of CCD because of its rarity.
PubMed: 26538892
DOI: 10.4103/0975-7406.163490 -
Journal of Dental Research Apr 2021The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous...
The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous genes associated with congenital craniofacial anomalies, our understanding of their etiology remains incomplete, and many affected individuals have an unknown genetic diagnosis. Here, we show that conditional loss of a Mediator complex subunit protein, Med23 in mouse neural crest cells (;), results in micrognathia, glossoptosis, and cleft palate, mimicking the phenotype of Pierre Robin sequence. messenger RNA and protein levels are both upregulated in neural crest cell-derived mesenchyme surrounding Meckel's cartilage and in the palatal shelves in ; mutant embryos compared to controls. Consistent with these observations, we demonstrate that Med23 binds to the promoter region of and represses Sox9 expression in vitro. Interestingly, Sox9 binding to β-catenin is enhanced in ; mutant embryos, which, together with downregulation of Col2a1 and Wnt signaling target genes, results in decreased proliferation and altered jaw skeletal differentiation and cleft palate. Altogether, our data support a cell-autonomous requirement for Med23 in neural crest cells, potentially linking the global transcription machinery through Med23 to the etiology and pathogenesis of craniofacial anomalies such as micrognathia and cleft palate.
Topics: Animals; Cleft Palate; Mediator Complex; Mesoderm; Mice; Neural Crest; Pierre Robin Syndrome; SOX9 Transcription Factor; Wnt Signaling Pathway
PubMed: 33155500
DOI: 10.1177/0022034520969109 -
International Journal of Clinical and... 2013Cleidocranial dysplasia syndrome (CCD) is a rare autosomal dominant disease with wide range of variability. Dentists are often the first to encounter the CCD patients,...
Cleidocranial dysplasia syndrome (CCD) is a rare autosomal dominant disease with wide range of variability. Dentists are often the first to encounter the CCD patients, some of whom do not show typical manifestations. Thus, dentists should be fully familiar with clinical manifestations and gene mutation. A 16-year-old girl was admitted for orthodontic treatment because of space in the dental arch and teeth irregularity. The introcession on the forehead and occiput suggests that she was a CCD patient. Clinical, radiological and genetic examinations were carried out in this girl and her family members and results showed delayed closure of the fontanel, hypoplastic clavicles and tooth anomalies of the girl and her mother. Genetic analysis revealed a 884C deletion in the exon 5 of the CBFA1/RUNX2 gene, which has never been reported in China. In this reported, the manifestations, diagnostic process and treatment of CCD were introduced according to the experience on the diagnosis of CCD in this family.
PubMed: 24260595
DOI: No ID Found -
Experimental & Molecular Medicine Jan 2023Haploinsufficiency of Runt-related transcription factor-2 (RUNX2) is responsible for cleidocranial dysplasia (CCD), a rare hereditary disease with a range of defects,...
Haploinsufficiency of Runt-related transcription factor-2 (RUNX2) is responsible for cleidocranial dysplasia (CCD), a rare hereditary disease with a range of defects, including delayed closure of the cranial sutures and short stature. Symptom-based treatments, such as a combined surgical-orthodontic approach, are commonly used to treat CCD patients. However, there have been few reports of treatments based on Runx2-specific regulation targeting dwarfism symptoms. Previously, we found that the miR338 cluster, a potential diagnostic and therapeutic target for postmenopausal osteoporosis, could directly target Runx2 during osteoblast differentiation in vitro. Here, we generated miR338;Runx2 mice to investigate whether inhibition of miR338 could rescue CCD defects caused by Runx2 mutation in vivo. We found that the dwarfism phenotype caused by Runx2 haploinsufficiency was recovered in miR338;Runx2 mice, with complete bone density restoration and quicker closure of fontanels. Single-cell RNA-seq analysis revealed that knockout of miR338 specifically rescued the osteoblast lineage priming ability of bone marrow stromal cells in Runx2 femurs, which was further confirmed by Osterix-specific conditional knockout of miR338 in Runx2 mice (OsxCre; miR338 ;Runx2). Mechanistically, ablation of the miR338 cluster in Runx2 femurs directly rescued the Hif1a-Vegfa pathway in Runx2 osteoblasts, as proven by gene expression profiles and ChIP and Re-ChIP assays. Collectively, our data revealed the genetic interaction between Runx2 and the miR338 cluster during osteoblast differentiation and implied that the miR338 cluster could be a potential therapeutic target for CCD.
Topics: Animals; Mice; Cleidocranial Dysplasia; Core Binding Factor Alpha 1 Subunit; Mutation; Osteoblasts; Osteogenesis
PubMed: 36599929
DOI: 10.1038/s12276-022-00914-w -
Congenital Anomalies Jul 2020Cleidocranial dysplasia (CCD) is a congenital anomaly characterized by the presence of impacted supernumerary teeth and delayed eruption of permanent teeth. However,...
Cleidocranial dysplasia (CCD) is a congenital anomaly characterized by the presence of impacted supernumerary teeth and delayed eruption of permanent teeth. However, there has been no detailed investigation on supernumerary teeth in patients with CCD using three-dimensional (3D) imaging techniques. The purpose of this study was to elucidate the morphology and position of supernumerary teeth using 3D images reconstructed from cone-beam computed tomography (CBCT) data in a group of five Japanese subjects (male, 3; female, 2; age, 15.0-25.4 years) with CCD. All five subjects exhibited supernumerary teeth (39 in total; average, 7.8; range, 1-15). All supernumerary teeth were impacted and existed as pairs with adjacent permanent teeth. Comparison of the size (the crown and dental-root lengths, the crown mesiodistal and buccolingual diameters), the number of cusps and dental roots, the position, and direction of supernumerary teeth in relation to the adjacent permanent teeth was analyzed. The results of relationship analyses revealed that, at sites other than the molar region, supernumerary teeth were positioned on the lingual and distal sides and supernumerary teeth resembled the morphology of their adjacent permanent teeth in terms of the number of cusps but were smaller than the adjacent permanent teeth. In the molar region, supernumerary teeth were microdontia, which were apparently small and obscure morphologically. In addition, while all adjacent permanent teeth exhibited normal direction, five supernumerary teeth exhibited inverse direction. The findings of this study will improve our understanding of the characteristics of CCD and provide important information for the pathophysiology and clinical treatment.
Topics: Adolescent; Adult; Cleidocranial Dysplasia; Cone-Beam Computed Tomography; Female; Humans; Imaging, Three-Dimensional; Male; Tooth; Tooth Abnormalities; Tooth, Supernumerary; Young Adult
PubMed: 31599034
DOI: 10.1111/cga.12358 -
International Journal of Clinical... 2010Cleidocranial dysplasia or mutational dysostosis or cleidocranial dysostosis is a generalized skeletodental dysplastic disorder, inherited in an autosomal dominant...
Cleidocranial dysplasia or mutational dysostosis or cleidocranial dysostosis is a generalized skeletodental dysplastic disorder, inherited in an autosomal dominant pattern. The expression of this disorder can vary widely in severity, even within the same family. This is a relatively rare disease and has no standard effective treatment option as of yet. Here we present a case report of affected mother and son with classical manifestations of the disease.
PubMed: 27625558
DOI: 10.5005/jp-journals-10005-1055 -
Orphanet Journal of Rare Diseases Dec 2018To study the present treatment situation and investigate a better orthodontic approach for patients with cleidocranial dysplasia (CCD) through systematically reviewing... (Review)
Review
OBJECTIVES
To study the present treatment situation and investigate a better orthodontic approach for patients with cleidocranial dysplasia (CCD) through systematically reviewing the published cases and to conclude the surgical-orthodontic treatment experience of cleidocranial dysplasia.
METHODS
A comprehensive search for studies published through to April 10, 2018 was conducted using the Pubmed, Web of Science, and Embase databases. The CCD cases treated with the approach combining surgical exposure and orthodontic treatment were concluded.
RESULTS
Eight papers and 9 finished cases were included to be compared with the present case. The age of cases ranged from 9 to 28 years. Clearing the way of eruption path in early age can facilitate the spontaneous eruption of impacted teeth. For adults, combined surgical-orthodontic treatment can achieve a nearly complete dentition and stable occlusal contact, but it is time consuming and needs surgical assistance. The combination of orthognathic surgery can reduce the difficulty of orthodontic treatment and treatment duration, as well as achieve a better facial profile.
CONCLUSION
Surgical exposure combined with orthodontic traction is an effective treatment for patient with CCD. Patient's age, demand, economic circumstances, and status of permanent dentition should be considered when making treatment plan.
Topics: Adult; Cleidocranial Dysplasia; Female; Humans; Male; Orthodontics; Young Adult
PubMed: 30514338
DOI: 10.1186/s13023-018-0959-3