Multiple Dental Anomalies Research Articles

Rare Variants in LRP4 Are Associated with Mesiodens, Root Maldevelopment, and Oral Exostoses in Humans

Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/β-catenin signaling, through its binding of WNT ligands, and to co-receptors LRP5/6, and WNT inhibitors DKK1, SOSTDC1, and SOST. LRP4 binds to SOSTDC1 and WNT proteins establishing a negative feedback loop between Wnt/β-catenin, Bmp, and Shh signaling during the bud and cap stages of tooth development. Consistent with a critical role for this complex in developing teeth, mice lacking Lrp4 or Sostdc1 have multiple dental anomalies including supernumerary incisors and molars. However, there is limited evidence supporting variants in LRP4 in human dental pathologies. We clinically, radiographically, and molecularly investigated 94 Thai patients with mesiodens. Lrp4 mutant mice were generated in order to study the effects of aberrant Lrp4 expression in mice. Whole exome and Sanger sequencing identified three extremely rare variants (c.4154A>G, p.Asn1385Ser; c.3940G>A, p.Gly1314Ser; and c.448G>A, p.Asp150Asn) in LRP4 in seven patients with mesiodens. Two patients had oral exostoses and two patients had root maldevelopments. Supernumerary incisors were observed in Lrp4 mutant mice. Our study implicates heterozygous genetic variants in LRP4 as contributing factors in the presentation of mesiodens, root maldevelopments, and oral exostoses, possibly as a result of altered WNT/β-catenin-BMP-SHH signaling.

Analysis of the feasibility of using deep learning for multiclass classification of dental anomalies on panoramic radiographs.

The aim of the feasibility study was to construct deep learning models for the classification of multiple dental anomalies in panoramic radiographs. Panoramic radiographs with single supernumerary teeth and/or odontomas were considered the "case" group; panoramic radiographs with no dental anomalies were considered the "control" group. The dataset comprised 150 panoramic radiographs: 50 each of no dental anomalies, single supernumerary teeth, and odontomas. To classify the panoramic radiographs into case and control categories, we employed AlexNet, which is a convolutional neural network model. AlexNet was able to classify whole panoramic radiographs into two or three classes, according to the presence or absence of supernumerary teeth or odontomas. The performance metrics of the three-class classification were 70%, 70.8%, 70%, and 69.7% for accuracy, precision, sensitivity, and F1 score, respectively, in the macro average. These results support the feasibility of using deep learning to detect multiple dental anomalies in panoramic radiographs.

Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia

BackgroundCleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (RUNX2) gene.ObjectiveIdentification and functional characterization of RUNX2 mutation associated with CCD.MethodsWe performed genetic testing of a patient with CCD using whole exome sequencing and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay.ResultsWe found a novel RUNX2 frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant RUNX2 and wild-type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter.ConclusionsWe explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in RUNX2 transactivation ability.

Surgical Management of Multiple Dental Anomalies in an Adolescent: A Case Report

Introduction: Unerupted or impacted teeth are commonly seen in young adolescents, whilst transposition of teeth is fairly uncommon. Paediatric patients presenting with an impacted or missing permanent tooth can complicate what may otherwise be a straightforward transition to the permanent dentition. In patients with multiple impacted teeth or transposition of teeth, the complexity of the case is increased further. Case Report: We present a case of impaction and transposition in an adolescent, managed by surgical technique only, using autotransplantation and corticotomy. This technique permitted rapid positional changes of the teeth to give an immediate aesthetic and functional improvement, with less reliance on longterm patient compliance. Conclusion: This report discusses the complexity of different treatment options that could have been undertaken. A multidisciplinary approach gave more treatment options to the patient, and total surgical management had many clinical advantages, along with a huge reduction in overall treatment time.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: dental anomalies in 8-year olds.

Children born with unilateral cleft lip and palate (UCLP) are reported to display several dental anomalies including agenesis, supernumeraries, as well as variations in dental size, shape, and path of eruption. The extensive sample of individuals with UCLP included in the Scandcleft randomized control trials offers the opportunity to study more rare conditions, which is seldom possible with limited samples. The aim was to study dental anomalies at 8 years of age in children born with UCLP included in the Scandcleft randomized control trials. Panoramic and intraoral radiographs from 425 individuals (279 males and 146 females) with a mean age of 8.1 years were assessed by four orthodontists regarding dental anomalies. Agenesis was found in 52.5 per cent and supernumerary teeth in 16.9 per cent of the participants. The cleft lateral was missing in 43.8 per cent and was found peg shaped in 44.7 per cent. The distribution of ectopic eruption was 14.6 per cent, mainly affecting maxillary first molars, while transposition was found in 3.4 per cent of the individuals. In addition, infraocclusion of one or several primary molars was registered in 7.2 per cent of the participants. We conclude that 8-year-old children born with UCLP display multiple dental anomalies. The Scandcleft sample allowed rarely studied conditions such as infraocclusion of primary molars and transposition to be studied in children born with UCLP. ISRCTN29932826.

Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia

ObjectivesCleidocranial dysplasia (CCD) is a congenital autosomal dominant skeletal disease characterized by multiple craniofacial and dental anomalies. Here, we investigated mutation of the runt-related transcription factor 2 (RUNX2) gene, which is considered responsible for most instances of CCD in patients, in a Chinese family with CCD. MethodsGenomic DNA was extracted from the peripheral blood lymphocytes of all participants, and mutation analysis was performed using whole-exome and Sanger sequencing. Biophysical predictions of the altered protein were analyzed using various bioinformatics tools, and direct sequencing via reverse transcription polymerase chain reaction (PCR) was performed for functional analysis of the mutation. To determine the function of the mutated protein, expression of RUNX2 and integrin-binding sialoprotein (IBSP) was investigated via quantitative PCR. ResultsWe identified a novel splicing mutation (c.581–9 T > G) in all affected members, with this RUNX2 mutation incorporating in a new splice site to replace the canonical splice site, thereby resulting in insertion of an 8-bp fragment within the terminal exon 5 splice-acceptor site and premature translation termination. qPCR results confirmed attenuated RUNX2 expression and IBSP overexpression in the peripheral blood lymphocytes of patients. ConclusionsThese results suggested that the newly identified splice-site mutation (c.581–9 T > G) in RUNX2 was responsible for CCD in this family through its alteration of RUNX2 activity and upregulated IBSP levels. These findings extend the mutational spectrum of the RUNX2 gene and might contribute to genetic diagnosis and counseling of families with CCD.

Multiple Dental Anomalies in a Patient with Down Syndrome

Multiple Dental Anomalies in a Patient with Down Syndrome

Multidisciplinary team approach in the oral rehabilitation of patients with cleidocranial dysplasia to achieve a functional aesthetic outcome

Cleidocranial dysplasia is a hereditary congenital disorder that results in delayed ossification of midline structures, and is caused by mutations in the RunX2 (runt-related transcription factor 2) gene located on the short arm of chromosome 6. Successful treatment depends on multidisciplinary assessment and a comprehensive staged treatment plan. We present a case series of 12 patients who were managed with a specifically tailored combination of surgery, orthodontics, and prosthodontics to provide a functional dentition and restore their smile and facial contour. Successful dental rehabilitation can be challenging in this group because patients often have multiple dental anomalies and a reduced quantity and density of alveolar bone. Rehabilitation with early intervention and a carefully planned multidisciplinary approach has been successful in the long term.

An assessment of the association of taurodontism with various dental anomalies, syndromes, systemic diseases and/or genetic diseases, and its role in identification

The aims of the study are to determine the association of taurodontism with numerical, dimensional, formal and structural dental anomalies, various syndromes, systemic diseases and/or genetic diseases, and to represent the clinical implications of the anomaly for clinicians and future forensic and genetic studies. The records of patients examined at the Department of Pedodontics, Faculty of Dentistry, Suleyman Demirel University were retrospectively analysed. A final sample of 837 patients with various dental anomalies, syndromes, systemic and/or genetic disorders was selected and evaluated to detect the presence of taurodontism. A chi-square goodness of fit test was performed to assess the distribution of this anomaly according to gender and localization. Further, Pearson’s correlation coefficient was calculated. Taurodontism was detected in 199 patients. It was mostly encountered with tooth agenesis. The differences of the distribution of this anomaly between the upper/lower jaws were statistically significant. Bilateral taurodontism was more frequent than unilateral taurodontism and was mainly seen on the maxillary first molars. No statistically significant correlation was found between the missing and taurodont teeth. Identifying individuals with multiple dental anomalies and/or with the syndromes and systemic diseases could serve as a guide for further forensic and genetic studies.

Primary double teeth in siblings: A report

Double teeth are developmental malformations affecting both primary and permanent dentition. This article describes primary double teeth in both the siblings of a family. A 5-year-old boy had a bilateral distribution of anomaly involving lower lateral incisor and canine. Radiographic analysis revealed that his right mandibular permanent lateral incisor was missing. His sister, a 3½-year-old girl, also had double teeth affecting mandibular left lateral incisor and canine. She displayed no other dental anomaly. The boy presented shovel-shaped maxillary permanent central incisors. Family involvement of double teeth is very rare. Double teeth in siblings and simultaneous occurrence of multiple dental anomalies probably show a hereditary etiology.

Multiple dental anomalies accompany unilateral disturbances in abducens and facial nerves: A case report

This article describes the oral rehabilitation of an 8-year-old girl with extensively affected primary and permanent dentition. This report is unique in which distinct dental anomalies including enamel hypoplasia, irregular dentin formation, taurodontism, hpodontia and dens in dente accompany unilateral disturbance of abducens and facial nerves which control the lateral eye movement, and facial expression, respectively. Keywords: enamel hypoplasia; irregular dentin formation; taurodontism; hypodontia; dens in dente; abducens and facial nerves;

La collection dentaire Hyacinthe Brabant : un outil pédagogique et scientifique majeur

Among the numerous specimens preciously preserved in the Anatomical and Embryological Museum of ULB, there lies also a dental collection assembled by Professor Hyacinthe Brabant. This collection, previously unlabelled, shows several dental anomalies and pathologies as well as tumours. The objective of our study was to conduct an inventory of this collection and to set up an electronic iconographic tool through the Iconography website of ULB. A descriptive study was carried out and it was based on the analysis of 125 models and 90 extracted human teeth. The inspection of the models showed some non-odontological tumours as well as multiple dental anomalies. The extracted teeth showed generalised, coronal or radicular anomalies. The conducted inventory allowed us to classify and label the specimens and therefore to showcase this dental collection which is unique owing to its rich content and didactic display. Finally, the iconographic site will be a useful tool to raise awareness about several dental pathologies and anomalies among students and young practionners.

Taurodontism: An Atypical Dental Phenotype in Apert Syndrome

Taurodontism is a dysgenesis of the molars, characterized by increased occlusal-apical dimension in the pulp chamber, explained by genetic disorder or atavism. It can be an isolated finding or associated with other dental anomalies and syndromes. In a 12-year-old dark-skinned female, clinical and radiographic examinations revealed acrobrachycephaly; syndactyly; maxillary retrusion; anterior open bite; posterior crossbite; Byzantine-arch palate; multiple dental anomalies of position (maxillary dental crowding and dental rotation) and shape (pronounced enamel bridge in lateral incisors and taurodontism in all second molar teeth); and bilateral elongation of the styloid process. Her parents were young adults and her mother had used illicit drugs and alcohol during pregnancy. The patient is undergoing treatment by her orthodontist. This rare case of taurodontism in a patient with Apert syndrome expands knowledge of the possible abnormalities associated with this pathological condition and underscores the role of nonspecific genetic pathways involved in syndromic taurodontism.

Giant mediastinal thymolipoma in a patient with Gardner's syndrome.

Gardner’s syndrome is a hereditary disorder inherited as an autosomal dominant with high penetrance and variable expression that is caused by a mutation of the adenomatous polyposis coli gene. It is characterized by gastrointestinal polyps associated with multiple osteomas, dental anomalies, and skin and soft tissue tumors. We present a case of 30-year-old female patient with Gardner’s syndrome who presented with a giant mediastinal thymolipoma. The tumor was completely excised through a bilateral posterolateral thoracotomy. There was no recurrence after 20 months of follow-up. We therefore suggest that physicians who regularly treat patients with Gardner’s syndrome carefully examine for thoracic manifestations.

Orthodontic and pediatric dental treatment approach in patient with multiple dental anomalies

The purpose of this clinical case report is to discuss the approach to oral rehabilitation of a patient with severe dental alterations such as enamel hypoplasia, change in shape, supernumerary tooth, dental ankylosis, agnesia and crowing in the incisor region. All of these problems compromised not only the esthetical and functional aspects of this patient, but his social relationships as well. Thus integrated planning between Pediatric Dentistry and Orthodontics made it possible to provide the best treatment alternative to recover the patient's stomatognathic system. Esthetic restorations were performed in the anterior tooth region with the use of resin composites, in addition to the use of removable orthodontic appliances, associated with serial extractions and supernumerary tooth removal. There were significant improvements in the esthetic and functional aspects of dentition, in addition to the patient demonstrating good evolution in his psychosocial condition, as he smiled and was more communicative during each follow-up appointment, also according to his mother's reports.

Multiple Dental Anomalies in Primary and Permanent Dentition: A Case Report

Multiple Dental Anomalies in Primary and Permanent Dentition: A Case Report

Permanent mandibular incisor with multiple anomalies – Report of a rare clinical case

BackgroundMorphological alterations in tooth structure involving either crown or root are common in the literature. But co-occurrence of multiple anomalies in a permanent mandibular central incisor is extremely rare. Case reportThis paper reports an unusual combination of multiple dental anomalies–talon cusp, dens invaginatus and macrodontia affecting both the crown and root of a permanent mandibular left central incisor of a 12-year old Indian boy. Case management has been described and the implications are discussed. ConclusionDiagnosis and treatment of teeth affected by multiple anomalies is a challenging proposition, requiring careful clinical and radiographic interpretation.

A rare case of multiple dental anomalies in non syndromic patient

Human dental anomalies are formative defects to variety of genetic and environmental factors. Multiple anomalies are seen in patient with chromosomal abnormalities or specific syndromes. Multiple odontogenic anomalies in non syndromic patient are unusual and rare. This paper reports a rare, unique and interesting case of multiple odontogenic anomalies such as bilateral macrodontia of maxillary central incisor, hypodontia, hyperdontia in lower anterior mandible, transposition in left anterior maxilla and taurodontism with molars in a single non syndromic young Indian female patient. Patients with multiple dental anomalies require multidisplinary treatment approaches such as surgical, orthodontic, endodontic, prosthodontic rehabilitation etc. Multiple dental anomalies in non syndromic patient are rare and needs early diagnosis and require multidisplinary approach. DOI: http://dx.doi.org/10.3329/bjms.v13i1.17444 Bangladesh Journal of Medical Science Vol. 13 No. 01 January2014: 95-98

Genome-wide Association Studies of Pit-and-Fissure- and Smooth-surface Caries in Permanent Dentition

While genetics clearly influences dental caries risk, few caries genes have been discovered and validated. Recent studies have suggested differential genetic factors for primary dentition caries and permanent dentition caries, as well as for pit-and-fissure- (PF) and smooth- (SM) surface caries. We performed separate GWAS for caries in permanent-dentition PF surfaces (1,017 participants, adjusted for age, sex, and the presence of Streptococcus mutans) and SM surfaces (1,004 participants, adjusted for age, education group, and the presence of Streptococcus mutans) in self-reported whites (ages 14 to 56 yrs). Caries scores were derived based on visual assessment of each surface of each tooth; more than 1.2 million SNPs were either successfully genotyped or imputed and were tested for association. Two homologous genes were suggestively associated: BCOR (Xp11.4) in PF-surface caries (p value = 1.8E-7), and BCORL1 (Xq26.1) in SM-surface caries (p value = 1.0E-5). BCOR mutations cause oculofaciocardiodental syndrome, a Mendelian disease involving multiple dental anomalies. Associations of other plausible cariogenesis genes were also observed for PF-surface caries (e.g., INHBA, p value = 6.5E-6) and for SM-surface caries (e.g., CXCR1 and CXCR2, p value = 1.9E-6). This study supports the notion that genes differentially affect cariogenesis across the surfaces of the permanent dentition, and nominates several novel genes for investigation.

Diagnosis and Treatment of Digitocutaneous Dysplasia, a Rare Infantile Digital Fibromatosis: A Case Report

Digitocutaneous dysplasia, also termed osseous terminal dysplasia with pigmentary defects, is a recently described pathology. In 1974, Bloem et al. [5] discussed the association between digital fibromas and pigmentary lesions. In 1998, Horii et al. [13] published a case report with similar characteristics associated with facial dysmorphia and metacarpal involvement. These authors were the first to describe a syndrome that embraced all these features. Recently, in 2010, Sun et al. [28] published the etiology of this pathology, FLNA gene mutation, with X-linked dominant transmission. This gene codifies filamin A, a protein essential in cytoskeleton formation. Published cases with digitocutaneous dysplasia are rare, with only 19 patients from nine different families [2, 3, 6, 7, 19, 21, 30], with exceptional isolated cases [15, 20]. In all of these cases, there were similar clinical findings that defined digitocutaneous dysplasia, such as multiple digital fibromas, dental anomalies, osseous alterations, and dysmorphic changes [13]. Fibromas associated with infantile digital fibromatosis have a high risk of recurrence when they are removed and they tend to autoresolve with time [20]. For fibromas associated with dysplasia digitocutaneous, the response to excision or other treatments is still not well defined. Consultation of a newborn female in our center, who presented with severe digital fibromas, encouraged us to carefully review the literature and examine the therapeutic possibilities.