Agenesia e fatores associados em pacientes portadores de fissura labiopalatina: uma revisão de literatura / Agenesis and associated factors in patients with cleft lip and palate: a review of the literature

Objetivo: verificar as principais agenesias dentárias e os fatores associados em portadores de fissura labiopalatina por meio de uma revisão de literatura. Métodos: foi realizada uma revisão de literatura utilizando as bases de dados PubMed, SciELO e Google Acadêmico. Revisão de literatura: foram incluídos 34 artigos, sendo 2 casos clínicos, 15 estudos retrospectivos, 10 revisões de literatura, 4 estudos de caso-controle e 5 estudos transversais; além de 3 referências escolhidas através de outras buscas para complementar a revisão. A partir dos estudos incluídos no trabalho, foi possível verificar que a maior prevalência ocorre no sexo masculino. E a fissura que mais acomete a população é a transforame incisivo. Pôde-se analisar também que não há causa exata, porém, existem fatores predisponentes, como os ambientais e os hereditários. Considerações finais: esta revisão de literatura poderá auxiliar os profissionais de saúde para a realização de diagnóstico e planejamento precoces, a fim de encontrar o melhor e mais eficiente tratamento para cada caso. O tratamento precoce, por uma equipe multidisciplinar, certamente garantirá uma melhor qualidade de vida aos pacientes.(AU)

Objective: to verify the main dental agenesis and associated factors in cleft lip and palate through a literature review. Methods: a literature review was carried out using PubMed, SciELO and Google Scholar databases. Literature review: 34 studies were included, 2 clinical studies, 1 retrospective study, 10 literature reviews, 4 case-control studies and 5 cross-sectional studies. In addition to 3 references chosen through other searches complementary to the review. From the included studies, it was verified a higher frequency of cleft lift and palate for the male sex, and a higher frequency of more severe clefts, such as the incisive transformation, in comparison to the labiopalatine. It can also be analyzed that there is no exact cause; however, there are environmental and hereditary predisposing factors. Final considerations: this literature review may help health professionals to carry out early diagnosis and treatment planning, in order to find the best and most efficient treatment for each case. Early treatment by a multidisciplinary team will certainly guarantee a better quality of life for patients.(AU)

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.

Rehabilitation of ectodermal dysplasia patients presenting with hypodontia: outcomes of implant rehabilitation part 1.

PURPOSE: This study has evaluated the pre and post perceptions of patients with ectodermal dysplasia (ED) who have been referred to Westmead Centre for Oral Health for treatment with dental implants. METHODS: Six patients with ED and hypodontia were treated with new maxillary complete dental prostheses or fixed implant prostheses, and a mandibular fixed dental prosthesis with implants. Patient perceptions were recorded with a 10cm visual analogue scale (VAS). All patients were asked to draw a line on the VAS which best described their feelings regarding aesthetics, chewing, diet and speech. RESULTS: Improvement in aesthetics was reported for all patients with change scores ranging from +9 to +4 points. Similarly, all patients reported an improvement in chewing ability with +6 point changes in 2 patients, and +8, +3, +7 and +1 in the other 4 patients. Five out of 6 patients reported less dietary restriction with 3 patients each indicating a change of +6 points, +4 points, +3 points, and 2 patients reporting +1 point change. Speech improved by +1 point for 3 patients, whilst 1 patient improved by +6 points, a further 2 patients scored no change. CONCLUSIONS: Patients with ED treated with dental implants reported encouraging outcomes post treatment after prostheses were fitted. Follow-up from 1.6 to 6.8 years has confirmed these improvements.

Tooth agenesis: A susceptible indicator for colorectal cancer?

CONTEXT/BACKGROUND: Tooth agenesis (excluding third molars) is a common congenital disorder that affects 2.2-10% of the general population. A number of different genes have been shown to be associated with cases of tooth agenesis including AXIN2, IRF6, FGFR1, MSX1, PAX9, and TGFA. Wingless/integration signaling gene, AXIN2, is linked to tooth agenesis and also to colorectal cancer (CRC). AIMS: To analyze the correlation between tooth agenesis and CRC. MATERIALS AND METHODS: The study included 50 individuals, who were divided into two groups. Group A: 25 individuals diagnosed with CRC and Group B: 25 individuals as a control group. The clinical details were recorded using preformed questionnaire, approved by ethical committee. Orthopantomogram was obtained for all the cases and controls. RESULTS: We observed that 16% of cases and 8% of controls reported having tooth agenesis and there was no statistical significance of difference between them (P = 0.384). Among the study group, 4% reported oligodontia and 12% cases reported hypodontia. In the control group 8% reported hypodontia, there was no incidence of oligodontia. Additional finding in the study group was that 24% cases had fissured tongue which was not seen in the control group. CONCLUSION: Individuals with tooth agenesis might have an increased risk for CRC. A larger epidemiological study along with genetic mapping and gene sequencing is necessary to rule out the risk and relationship between tooth agenesis and CRC.

WNT10B mutations associated with isolated dental anomalies.

Isolated hypodontia is the most common human malformation. It is caused by heterozygous variants in various genes, with heterozygous WNT10A variants being the most common cause. WNT10A and WNT10B are paralogs that likely evolved from a common ancestral gene after its duplication. Recently, an association of WNT10B variants with oligodontia (severe tooth agenesis) has been reported. We performed mutational analysis in our cohort of 256 unrelated Thai families with various kinds of isolated dental anomalies. In 7 families afflicted with dental anomalies we detected 4 heterozygous missense variants in WNT10B. We performed whole exome sequencing in the patients who had WNT10B mutations and found no mutations in other known hypodontia-associated genes, including WNT10A, MSX1, PAX9, EDA, AXIN2, EDAR, EDARADD, LPR6, TFAP2B, LPR6, NEMO, KRT17, and GREM2. Our findings indicate that the variants c.475G>C [p.(Ala159Pro)], found in 4 families, and c.1052G>A [p.(Arg351His)], found in 1 family, are most probably causative. They also show that WNT10B variants are associated not only with oligodontia and isolated tooth agenesis, but also with microdontia, short tooth roots, dental pulp stones, and taurodontism.

Disturbances of dental development distinguish patients with oligodontia-ectodermal dysplasia from isolated oligodontia.

OBJECTIVE: To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). SETTING AND SAMPLE POPULATION: A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. METHODS: The phenotype of dental development was assessed for the frequency of missing a certain tooth, dental age, development of each tooth present, abnormal size and abnormal shape of teeth. The data were analysed building linear, ordinal and logistic regression models. RESULTS: Compared to patients with isolated oligodontia, patients with oligodontia-ED missed more frequently central incisors and second molars in both jaws, and lateral incisors in the mandible (P < .05). Oligodontia-ED was associated with delayed development of the permanent dentition (ß = -0.10; 95% CI: -0.17, -0.03). Specifically, the maxillary teeth: right central incisor, right lateral incisor, right second premolar and left second premolar were delayed approximately from 2 to 4 developmental stages. In addition, the left mandibular second premolar was 3 developmental stages delayed. Abnormal shape of teeth was 7 times more evident in patients with oligodontia-ED compared to patients with isolated oligodontia (OR = 6.54; 95% CI: 2.34, 18.28). The abnormal size of teeth was not a distinctive characteristic for oligodontia-ED. CONCLUSIONS: Oligodontia-ED distinguishes from isolated oligodontia by more disturbances in dental development. The abnormal shape of incisors and canines in a patient with oligodontia can raise suspicions for accompanying ectodermal abnormalities.

Evaluation of dental age and associated developmental anomalies in subjects with impacted mandibular canines.

OBJECTIVES: To assess the null hypothesis that there is no difference in the rate of dental development and the occurrence of selected developmental anomalies related to shape, number, structure, and position of teeth between subjects with impacted mandibular canines and those with normally erupted canines. MATERIALS AND METHODS: Pretreatment records of 42 subjects diagnosed with mandibular canines impaction (impaction group: IG) were compared with those of 84 subjects serving as a control reference sample (control group: CG). Independent t-tests were used to compare mean dental ages between the groups. Intergroup differences in distribution of subjects based on the rate of dental development and occurrence of selected dental anomalies were assessed using χ(2) tests. Odds of late, normal, and early developers and various categories of developmental anomalies between the IG and the CG were evaluated in terms of odds ratios. RESULTS: Mean dental age for the IG was lower than that for the CG in general. Specifically, this was true for girls (P < .05). Differences in the distribution of the subjects based on the rate of dental development and occurrence of positional anomalies also reached statistical significance (P < .05). The IG showed a higher frequency of late developers and positional anomalies compared with controls (odds ratios 3.00 and 2.82, respectively; P < .05). CONCLUSIONS: The null hypothesis was rejected. We identified close association of female subjects in the IG with retarded dental development compared with the female orthodontic patients. Increased frequency of positional developmental anomalies was also remarkable in the IG.

[Tooth eruption disturbances and syndromes]. / Eruptiestoornissen en syndromen.

In the tooth eruption mechanism, various disturbances can appear as a result of gene mutations, a consequence of which can be that tooth eruption does not occur. There are 5 syndromes which involve the complete failure of several or even all teeth to erupt, specifically: cleidocranial dysplasia, Gardner's syndrome, osteopetrosis, mucopolysaccharidosis and GAPO syndrome. Some are very rare and will seldom be encountered in a dental practice, but they show how vulnerable the tooth eruption mechanism is. Dentists are generally the ones who identify a tooth eruption problem in a patient. Since syndromes can be associated with other disorders, additional investigation by a clinical geneticist is always important when a syndrome is suspected.

Task dependent muscular volume in unilateral edentulous patientsby magnetic resonance imaging (MRI) / Volume muscular função-dependente em pacientes desdentadosunilaterais por ressonância magnética (RM)

Objective: To assess the sequelae of unilateral chewing on muscles of mastication via comparing the approximatemuscular volume (AMV) of the masseter (MM), medial pterygoid (MPM), temporalis (TM),superior and inferior lateral pterygoid muscles (SLPM/ILPM) bilaterally using MRI. Materials and methods:Twenty patients (16 females and 4 males) were selected from outpatient dental clinics of Kaser AlAini Hospitals, Cairo University, complaining from being unilaterally edentulous for one year or more. Alsosix fully dentate individuals (2 males and 4 females) were selected as control group. Magnetic ResonanceImaging (MRI) of the masticatory muscles was performed followed by measuring the approximate musclevolume (AMV) for each muscle bilaterally using the planimetry method. Results: Showed increase in theapproximate muscular volume (AMV) of the dentate side in both right side and left side edentulous patients.Conclusion: Our study shows the effect of long term unilateral chewing on decreasing the AMV in the nonfunctioningside, suggesting that measuring the approximate masticatory muscle volume using MRI couldbe helpful in detection of long-term functional disability of each muscle in comparison to adjacent muscles.

Objetivo: Avaliar as sequelas da mastigação unilateral sobre os músculos da mastigação por meio da comparaçãodo volume aproximado muscular (AMV) do músculo masseter (MM), pterigóideo medial (MPM), temporal(TM), músculos pterigóideos laterais superior e inferior (SLPM/ILPM) bilateralmente usando ressonânciamagnética. Materiais e métodos: Vinte pacientes (16 mulheres e 4 homens) foram selecionados a partir deambulatórios odontológicos do Hospital Kaser Al Aini, Universidade do Cairo; todos os participantes eram unilateralmentedesdentados há um ano ou mais. Também, seis indivíduos totalmente dentados (2 homens e 4mulheres) foram selecionados como grupo controle. Imagem por Ressonância Magnética (RM) dos músculosmastigatórios foi realizada seguido pela medição do volume muscular aproximada (AMV) para cada músculobilateral utilizando o método de planimetria. Resultados: Foi observado aumento no volume aproximadomuscular (AMV) do lado dentado em ambos os lados direito e esquerdo de desdentados laterais. Conclusão:Este estudo mostra o efeito em longo prazo da mastigação unilateral na diminuição da AMV no lado nãofuncional, o que sugere que a medição do volume muscular mastigatório aproximado usando ressonânciamagnética pode ser útil na detecção de deficiência funcional de cada músculo em comparação com músculosadjacentes em longo prazo.

Root resorption of primary molars without successor teeth. An experimental study in the beagle dog.

Tooth agenesis is a common craniofacial congenital malformation in humans, but little is known about the mechanisms of root resorption in this condition. The purpose of this study was to investigate the mechanisms of root resorption in primary molars without successors. An animal model without permanent tooth germs was established by surgery in beagles. The times of onset of primary molar root resorption, with and without successors, were compared. The distribution of immune cells, odontoclasts, and their activating factors were determined by histochemistry and immunohistochemistry. Root resorption of primary mandibular molars without successors began later than physiological resorption. In primary molars without permanent germs, odontoclasts and immune cells were present mainly in the apical pulp at the start of root resorption, whereas in control teeth receptor activator of nuclear factor-κB ligand (RANKL)-positive cells were found mainly in the region of the periodontal ligament. CD14(+) and CD3(+) cells were found in both the pulp and the periodontal ligament region. These results suggest that the dental pulp of primary molars, as well as immune cells, may play an important role in root resorption in primary molars without permanent tooth germs.

Dental development in hemifacial microsomia.

Hemifacial microsomia (HFM) is a congenital disorder marked by facial asymmetry. Whether facial asymmetry accounts for asymmetrical dental development is unknown. There are few data on dental development relative to mandibular development or severity of HFM, or on development over time. We hypothesized that when mandibular development was severely disturbed, local dental development was also affected. We compared dental development scores between affected and non-affected mandibular sides in patients with HFM (n = 84) and compared these data with those collected from Dutch control children (n = 451). Logistic functions were constructed for dental age over time for all four Pruzansky/Kaban types. The results showed a tendency toward delayed dental development in Pruzansky/Kaban types IIb and III at younger ages. The temporary delay of tooth formation in patients with severe forms of HFM and the distribution of agenic teeth suggest an interaction between mandibular and dental development.

Premolar hypodontia is a common feature in Sotos syndrome with a mutation in the NSD1 gene.

The major diagnostic manifestations in Sotos syndrome include frontal bossing, downward slanting palpebral fissures, a prominent jaw, learning disability, and childhood overgrowth. Over 90% of clinically diagnosed patients have an abnormality in the NSD1 gene. We investigated the dental manifestations of this disorder and found one or several premolar teeth were absent in 9 out of 13 (69%) affected children and adolescents. A heterozygous mutation in the NSD1 gene was identified in 12 patients, including all patients with hypodontia. The severity of the hypodontia seemed to increase with the severity of aberration of the NSD1. More than 50% of the patients had enamel defects or excessive tooth wear. Dental age, based on tooth formation, was within the normal range. A characteristic occlusion for Sotos syndrome could not be identified. As agenesis of premolars was a common feature in these patients affected with Sotos syndrome, we recommend panoramic radiography at the age of 7 years. If premolars are missing, proper preventive and restorative care is necessary to maintain the deciduous molars.

Head and neck manifestations and quality of life of patients with ectodermal dysplasia.

OBJECTIVES: Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by deficient ectodermal and mesodermal development. Studies examining resultant otolaryngologic issues are few. The objectives of this study were to delineate the head and neck manifestations and quality of life in EDs. STUDY DESIGN AND SETTING: For 75 individuals, comprehensive histories were taken and otolaryngologic examinations were performed, and subjects rated their otolaryngologic symptom severity. A validated quality of life instrument (SF-8) was administered. RESULTS: The majority of subjects had a diagnosis of hypohidrotic ED (72%). Otolaryngologic conditions included otitis media (28%), cerumen impaction (48%), nasal obstruction/crusting (51%), heat intolerance (76%), and eczema (39%). Physical findings included peg teeth/hypodontia (76%), alopecia (41%), nasal crusting (41%), and saddle nose deformity (44%). Quality of life scores were generally high. Overall, health was rated "good to excellent" by 87 percent. CONCLUSION: Patients with ED frequently experience significant otolaryngologic symptoms, although most patients report a good quality of life. SIGNIFICANCE: A greater understanding of the otolaryngologic issues in ED should help facilitate diagnosis and improve management.

Mandibular morphology and growth with and without hypodontia in subjects with Pierre Robin sequence.

INTRODUCTION: Mandibular micrognathia is the hallmark of Pierre Robin sequence (PRS). A high prevalence of mandibular hypodontia has been reported in subjects with PRS. The hypothesis of this study is that the morphology of the mandible in subjects with PRS and mandibular hypodontia is different from that in subjects with PRS but without mandibular hypodontia. METHODS: The study was conducted at the craniofacial center of The Hospital for Sick Children in Toronto. The study sample comprised 16 caucasian children with nonsyndromic PRS (7 boys, 9 girls) with mandibular hypodontia and 18 white children with nonsyndromic PRS (6 boys, 12 girls) without hypodontia. Longitudinal lateral cephalograms were available before orthodontic treatment (T1; mean age, 11.7 years) and after orthodontic treatment but before orthognathic surgery (T2; mean age, 16.6 years). A new, customized cephalometric analysis with additional landmarks and measurements to study mandibular morphology was performed. Differences in measurements were studied by using analysis of variance adjusted for age and sex. RESULTS: Cephalometric measurements were smaller in the group with mandibular hypodontia at T1: mandibular length (3.36 mm, P = .04), ramal length (2.78 mm, P = .04), posterior facial height (3.97 mm, P = .03), and mandibular molar eruption (1.96 mm, P = .02). At T2, the differences increased: mandibular length (4.56 mm, P = .02), ramal length (4.04 mm, P = .002), posterior facial height (5.98 mm, P = .001), and mandibular molar eruption (2.08 mm, P = .04). Comparison of growth increments between the 2 groups from T1 to T2 showed a greater cranial base deflection increment in the group with mandibular hypodontia (0.88 degrees, P = .02) and a larger posterior facial height increment in the group without mandibular hypodontia (2.02 mm, P = .04). CONCLUSIONS: Children with nonsyndromic PRS with mandibular hypodontia had smaller mandibles than children with nonsyndromic PRS and normal complements of mandibular teeth. Their patterns of growth did not improve during adolescence, and the magnitude of differences increased.

Child with De Novo t(1;6)(p22.1;p22.1) translocation and features of ectodermal dysplasia with hypodontia and developmental delay.

We report on a 6.5-year-old girl with a balanced translocation between the short arms of chromosomes 1 and 6. She was referred for genetics evaluation because of developmental speech delay and congenital absence of several deciduous and permanent teeth. She was very sensitive to noise (hyperacusis), had poor hair and nail growth, decreased sweating, and turned very red with high fever. She had microcephaly (head circumference at the second centile; weight and height were at 25th centile), short palpebral fissures, epicanthal folds, sparse eyelashes, large ears, partial anodontia, short finger and toenails, and dry skin. She had mild developmental delay. Family history was significant for learning problems in two paternal uncles, one paternal aunt, and several paternal cousins. Thyroid studies, calcium, phosphorus, and alkaline phosphatase levels were normal. Her karyotype was 46,XX,t(1;6)(p22.1;p22.2), and parental karyotypes were normal. This apparently balanced translocation may have resulted in either a submicroscopic loss or disruption of a gene or genes involved in ectodermal dysplasia. There are no reported cases of ectodermal dysplasia associated with this chromosome rearrangement.

Analysis of facial growth in subjects with syndromic ectodermal dysplasia: a longitudinal analysis.

OBJECTIVE: To examine the craniofacial growth pattern of patients diagnosed with syndromic ectodermal dysplasia. DESIGN: Mixed longitudinal analysis of lateral cephalograms. SETTING: The data were analysed using a multilevel modelling technique with the MLwiN application software and the results presented numerically and graphically. SAMPLE POPULATION: All 61 subjects had severe hypodontia with the number of absent teeth (excluding third molars) ranging from 6 to 28 (mean = 15.4). At presentation the subjects had a mean age of 133 months and were followed longitudinally for between one and five subsequent occasions (mean 2.66 occasions; mean age at completion of observation 207 months). OUTCOME MEASURES: Lateral cephalograms taken at each visit. EXPERIMENTAL VARIABLES: Analysis of four angular measurements and four linear measurements, together with one calculated ratio. RESULTS: Growth curves are presented showing the trends of craniofacial growth. CONCLUSIONS: The most significant findings were for a universal tendency for the individuals to undergo a change in sagittal relationship of the jaws, becoming markedly more Class III with time. We have also demonstrated a significant difference in growth between the anterior and posterior face heights indicating that the subjects have a tendency to an anterior growth rotation.

Dental development after successful treatment of infantile osteopetrosis with bone marrow transplantation.

A 3-week-old boy was diagnosed with congenital osteopetrosis. He underwent a bone marrow transplant at 6 weeks of age. At 3 years of age the primary teeth had all erupted, but the canines and the first molars totally lacked root development. The teeth were smaller in size and had evidence of both enamel hypomineralization and hypoplasia. In the permanent dentition, multiple missing teeth were found. The incisors were conical and the mandibular laterals were extremely small. All permanent teeth had normal eruption. This case shows that dental development and eruption of teeth can be reconstituted in a child with congenital osteopetrosis. Bone marrow transplantation induces normalization of osteoclast function, which is a prerequisite for normal dental development and eruption of teeth.

Oligodontia is associated with extra-oral ectodermal symptoms and low whole salivary flow rates.

INTRODUCTION: Ectodermal dysplasias (EDs) involve abnormal development of hair, teeth, nails, and sweat glands. OBJECTIVES: (1) To investigate the frequency of extraoral ectodermal symptoms in persons with oligodontia (>6 congenitally missing teeth). (2) To examine whole salivary flow rates in oligodontia patients, with special emphasis on persons with EDs. SURVEY GROUP AND METHODS: Sixty-eight persons with oligodontia and 39 healthy control persons were included. All participants underwent an interview, general and oral examinations, and whole salivary secretory tests. RESULTS: Thirty-nine (57%) of the oligodontia patients had disturbances in either hair, nails and/or sweat production in addition to teeth and were classified as the ED group. The remaining 29 oligodontia patients had no obvious signs of EDs (non-ED group). The prevalences of dry skin, asthma and eczema were higher, and whole salivary secretory rates lower, in the ED group as compared to the control group. Intermediate values were observed in the non-ED group. Incisors, canines and molars were more frequently missing in the ED group than in the non-ED group, whereas no differences were observed in the frequency of missing premolars. Negative correlations between the number of missing teeth and unstimulated and chewing stimulated whole salivary secretory rates were found.

Alveolar bone growth in response to endosteal implants in two patients with ectodermal dysplasia.

The occurrence of alveolar bone growth after placement of endosteal mandibular implants in two edentulous children is reported. The fact that alveolar bone growth occurred in the absence of natural teeth suggests that its growth and preservation is dependent upon biomechanical factors rather than the presence of teeth, as is traditionally thought.