Single median maxillary central incisor: new data and mutation review

BACKGROUND: Single median maxillary central incisor (SMMCI) is a rare anomaly that may occur alone or associated with other conditions, frequently as part of the holoprosencephaly (HPE) spectrum. However, it has been suggested that SMMCI alone, or associated with some midline defects, may be considered a different entity from HPE (OMIM: 147250). Families with SMMCI, without HPE cases, are difficult to counsel for the risk of HPE in future generations because the same midline defects described as part of the "SMMCI syndrome" can also be part of the HPE spectrum. METHODS: We screened five cases of SMMCI for mutations in three HPE genes, SHH, TGIF, and SIX3. RESULTS: A missense mutation c.686C>T was found in the gene SIX3 of one patient, which did not differ from the accepted 20% of known HPE gene mutations among all HPE cases. Our results and an extensive literature review of gene mutations in patients with SMMCI showed that 27/28 of them were in HPE genes: SHH (n = 21), SIX3 (n = 3), TGIF (n = 1), GLI2 (n = 1), and PTCH (n = 1), and only one in the SALL4 gene. CONCLUSIONS: The clinical findings in patients with SMMCI without HPE in families with mutations in HPE genes cannot be distinguished from the findings reported in the SMMCI syndrome. Therefore, persons with SMMCI and their relatives should be carefully investigated for related midline disorders, especially of the HPE spectrum, and all known HPE genes screened.     

Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation

The term "supernumerary teeth" describes production of more than the normal number of teeth in the primary or permanent dentitions. Their aetiology is not understood. Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist that plays important roles in the local regulation of BMP signaling by binding and neutralizing BMP activities, and also serves as a modulator of Wnt signaling. We report here that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor tooth. We confirmed that the USAG-1 expression is localized to the epithelium and mesenchyme of the rudimentary maxillary incisor tooth organ formation. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. Based upon these results, we conclude that USAG-1 controls the number of teeth in the maxillary incisor region by regulating apoptosis.     

Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome

Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome: In this report we present the prenatal second trimester echographic diagnosis of laryngeal atresia in a male fetus with multiple associated congenital anomalies: oesophageal atresia, crossed fused ectopy of the right kidney, mild cutaneous syndactyly of fingers III-V and toes II-III, distinct facial appearance and single umbilical artery. Bilateral voluminous echogenic lungs were the major echographic diagnostic sign. The associated multiple congenital anomalies were not diagnostic for a distinct, recognizable multiple malformation syndrome.     

Cat eye syndrome and growth hormone deficiency with pituitary anomalies: A case report and review of the literature

Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted.     

BILIARY TRACT ANOMALIES—The Utilization of Modern Techniques in Differential Diagnosis

The diagnostic aids used in dealing with biliary disease in adults were applied to the study in infants of the principal congenital anomalies of the biliary tract such as choledochal cyst, biliary atresia and biliary stenosis.Choledochal cysts were distinguished from other upper abdominal masses occurring in childhood by the use of intravenous cholecystography.Since the clinical manifestations in infants with biliary atresia or stenosis are almost identical to those associated with the obstructive phase of neonatal hepatitis, the problem of differentiation is difficult. The serial total serum bilirubin curve, a careful analysis of the pigment content of feces and urine and duodenal intubation for bilirubin determinations were found to be useful in making the distinction. Operative cholangiograms were helpful in some cases. Frozen section examinations of liver tissue during operation were of little value except to demonstrate certain unusual cases of intrahepatic biliary atresia. Routine liver function studies, including serum transaminase determination in a limited number of cases, did not help in differentiation.     

Biliary tract anomalies: the utilization of modern techniques in differential diagnosis

The diagnostic aids used in dealing with biliary disease in adults were applied to the study in infants of the principal congenital anomalies of the biliary tract such as choledochal cyst, biliary atresia and biliary stenosis. Choledochal cysts were distinguished from other upper abdominal masses occurring in childhood by the use of intravenous cholecystography. Since the clinical manifestations in infants with biliary atresia or stenosis are almost identical to those associated with the obstructive phase of neonatal hepatitis, the problem of differentiation is difficult. The serial total serum bilirubin curve, a careful analysis of the pigment content of feces and urine and duodenal intubation for bilirubin determinations were found to be useful in making the distinction. Operative cholangiograms were helpful in some cases. Frozen section examinations of liver tissue during operation were of little value except to demonstrate certain unusual cases of intrahepatic biliary atresia. Routine liver function studies, including serum transaminase determination in a limited number of cases, did not help in differentiation.     

Canine reduction in early man: A critique of three mechanical models

The possibility that projecting maxillary canines interfere with either a «rotary chewing» form of molar occlusion or the lateral excursion of the mandible has been used to suggest two dietary (non-weapon) selection models for canine reduction in the earliest male humans. A third model explaining canine reduction is based on the idea that a projecting mandibular canine could interfere with its tip-to-tip occlusion with the maxillary lateral incisor. In this paper, these three mechanical models are critically reexamined in light of more recent studies of occlusion in extant primates, detailed observations of anterior tooth morphology and wear in Miocene to Recent anthropoids, cheek tooth microwear inA. afarensis, and the currently accepted phylogeny and fossil record of the great apes and man.     

Interaction between Foxc1 and Fgf8 during Mammalian Jaw Patterning and in the Pathogenesis of Syngnathia

Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the maxillary prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 – Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of other congenital craniofacial anomalies, including temporomandibular joint agenesis.     

Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse

Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist, and also modulates Wnt signaling. We previously reported that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. We confirmed that BMPs were expressed in both the epithelium and mesenchyme of the rudimentary incisor at E14 and E15. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Wnt signaling as demonstrated by the nuclear localization of β-catenin was also up-regulated. Inhibition of BMP signaling rescues supernumerary tooth formation in E15 incisor explant culture. Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model.     

Immunohistochemical localization of Pax6 in the developing tooth germ of mice

Recent studies have reported that supernumerary teeth were observed in the maxillary incisor area in several Pax6 homozygous mutant mouse and rat strains. To date, it remains unknown whether Pax6 is expressed during tooth development in any species. The study aimed to analyze the expression of Pax6 during mouse incisor and molar development. C57BL/6J mouse embryos on days E12.5, E13.5, E14.5, E16.5 and E18.5 were produced. Heads from these embryos, as well as from P1.5 mice, were processed for paraffin wax embedding (N ≥ 3 for each stage) and prepared for immunohistochemistry. Pax6 immunostaining was found in all tooth germs examined. At the E12.5 dental placode, E13.5 bud stage, E14.5 cap stage and E16.5 early bell stage, Pax6 was expressed in ectodermally derived tissues of tooth germs and oral epithelia adjacent to the tooth germs. Cells in the underlying dental ectomesenchyme that showed Pax9 expression were Pax6 negative. At E18.5 and P1.5, Pax6 was expressed in more differentiated ameloblasts and cells of the stratum intermedium and stellate reticulum that were derived from the oral epithelium, as well as in mesenchyme-derived differentiated odontoblasts. Pax6 expression was also observed in the submandibular gland, tongue filiform papilla and hair follicle at E16.5 and P1.5. The present study demonstrated that Pax6 was expressed in incisor and molar germs during mouse tooth development. The results provide a basis for exploring the function of Pax6 during tooth development.     

Static intraspecific allometry of jaws and teeth in Cercopithecus aethiops

Adult static intraspecific allometry of jaw size and tooth area was evaluated in a sample of 100 Cercopithecus aethiops crania (50 male, 50 female). Tooth areas were calculated from mesiodistal and buccolingual measurements of all the teeth in both arcades and were scaled to four viscero-cranial measurements: bimaxillary breadth, maxillo-alveolar length, mandibular length and bigonial width. Allometric coefficients calculated for jaw dimensions alone indicate tighter viscerocranial integration in females than in males. A finding of note was that half of the variation in maxillo-alveolar length may be accounted for by variation in mandibular length: females are isometric, males negatively allometric.
A similar degree of allometric mosaicism was found when maxillary incisor size was scaled to maxillary length and width. In females, the relationship was negatively allometric, whilst incisor size in males was found to be unrelated to either. Negative allometry characterized the relationship of canine base area to jaw length in both sexes, with males additionally being positively allometric to mandibular width.
The scaling of postcanine tooth areas to jaw length was characterized by a dichotomous pattern: males showed significant mandibular integration whilst females showed only significant maxillary integration. Compensatory tooth size interaction between maxillary canine base area and the summed incisor and postcanine areas was suggested by the significant negative allometric relation between them.     

Data on morphometric analysis of anterior teeth from Hazaribag College of Dental Sciences and Hospital,jharkhand

It is of interest to document data on morphometric (measurement of external form) analysis of maxillary and mandibular anterior teeth collected from a dental set up using mesio-distal (MD) dimension. The mesiodistal dimensions of all permanent anterior teeth (central incisor, lateral incisor and canine) of 25 males and 25 females patients were recorded using digital vernier calipers. Data were charted and statistical analysis was done using Mann Whitney U test. Data shows sexual dimorphism for every tooth between males and females. However, dimorphism was exhibited only in maxillary and mandibular canine, mandibular central incisors, and lateral incisor. Hence,odontometric parameters offer simple, reliable and cost-effective in forensic investigation for recording gender discrimination.     

实验性延期再植牙大鼠模型组织学分析方法的建立

摘要 目的：建立延期再植牙大鼠模型并观察牙根不同部位预后特点,比较不同组织学分析方法的合理性,为相关临床、基础研究提供参考。方法：6周龄雄性SD大鼠10只,右侧上颌切牙脱位后延期再植,术后30 d 处死,分离上颌骨;利用micro CT从不同截面分析上颌切牙及牙周组织生理结构。切片后通过HE染色、MASSON染色、TRAP染色观察比较牙根不同部位愈合情况、破骨细胞分布情况。结果：大鼠切牙唇侧有釉质覆盖,腭侧牙骨质覆盖,且再植牙不同部位愈合情况、破骨细胞分布有差异,其牙根唇侧未见明显吸收,腭侧根中1/3相比根尖1/3和根颈1/3吸收范围更广、深度更深,破骨细胞分布数量更多,差异具有统计学意义（P<0.001）,提出了腭侧中1/3作为牙根吸收组织学分析区域的合理性。结论：本实验比较了再植牙大鼠模型牙根不同部位的愈合情况,提出了一种较为合理的组织学分析方法,能客观反映再植牙愈合方式,为进一步研究再植牙愈合机理提供了较好的研究模型。     

Isolation and Culture of Dental Epithelial Stem Cells from the Adult Mouse Incisor

Understanding the cellular and molecular mechanisms that underlie tooth regeneration and renewal has become a topic of great interest^1-4, and the mouse incisor provides a model for these processes. This remarkable organ grows continuously throughout the animal''s life and generates all the necessary cell types from active pools of adult stem cells housed in the labial (toward the lip) and lingual (toward the tongue) cervical loop (CL) regions. Only the dental stem cells from the labial CL give rise to ameloblasts that generate enamel, the outer covering of teeth, on the labial surface. This asymmetric enamel formation allows abrasion at the incisor tip, and progenitors and stem cells in the proximal incisor ensure that the dental tissues are constantly replenished. The ability to isolate and grow these progenitor or stem cells in vitro allows their expansion and opens doors to numerous experiments not achievable in vivo, such as high throughput testing of potential stem cell regulatory factors. Here, we describe and demonstrate a reliable and consistent method to culture cells from the labial CL of the mouse incisor.     

A Global Numerical Analysis of the “Central Incisor / Local Maxillary Bone” System using a Meshless Method

In this work the maxillary central incisor is numerically analysed with an advance discretization technique – Natural Neighbour Radial Point Interpolation Method (NNRPIM). The NNRPIM permits to organically determine the nodal connectivity, which is essential to construct the interpolation functions. The NNRPIM procedure, based uniquely in the computational nodal mesh discretizing the problem domain, allows to obtain autonomously the required integration mesh, permitting to numerically integrate the differential equations ruling the studied physical phenomenon. A numerical analysis of a tooth structure using a meshless method is presented for the first time. A two-dimensional model of the maxillary central incisor, based on the clinical literature, is established and two distinct analyses are performed. First, a complete elasto-static analysis of the incisor/maxillary structure using the NNRPIM is evaluated and then a non-linear iterative bone tissue remodelling analysis of the maxillary bone, surrounding the central incisive, is performed. The obtained NNRPIM solutions are compared with other numerical methods solutions available in the literature and with clinical cases. The results show that the NNRPIM is a suitable numerical method to analyse numerically dental biomechanics problems.     

Microform holoprosencephaly in mice that lack the Ig superfamily member Cdon

Holoprosencephaly (HPE), the most common developmental defect of the forebrain and midface, is caused by a failure to delineate the midline in these structures. Despite the identification of several HPE genes, its genetic basis is largely unknown. Furthermore, the phenotype of affected individuals is highly variable, even within pedigrees. Facial defects in HPE range from cyclopia and proboscis in severe cases to solitary median maxillary central incisor in individuals with microforms of HPE. Cdon (also known as Cdo), an Ig superfamily member, is a component of a cell surface receptor that positively regulates skeletal myogenesis. Cdon is also highly expressed in the frontonasal and maxillary processes (FNP and MXP, respectively) of the developing mouse embryo, structures that contain signaling centers that pattern the face. We report here that mice homozygous for targeted mutations of Cdon display the hallmark facial defects associated with microforms of HPE. This is the first example of a mouse mutant with this phenotype, and this finding implicates a new family of receptors in development of the facial midline and suggests a potential role for Cdon in the pathogenesis and expressivity of HPE in humans.     

Combined deletion 18q22.2 and duplication/triplication 18q22.1 causes microcephaly,mental retardation and leukencephalopathy

Chromosome 18 abnormalities rank among the most common autosomal anomalies with 18q being the most frequently affected. A deletion of 18q has been attributed to microcephaly, mental retardation, short stature, facial dysmorphism, myelination disorders, limb and genitourinary malformations and congenital aural atresia. On the other hand, duplications of 18q have been associated with the phenotype of Edwards syndrome. Critical chromosomal regions for both phenotypes are contentious. In this report, we describe the first case of an 11-year old male with a combined interstitial duplication 18q22.1, triplication 18q22.1q22.2 and terminal deletion 18q22.2q23 with phenotypic features of isolated 18q deletion syndrome and absence of phenotypic features characteristic of Edwards syndrome despite duplication of the suggested critical region. This report allows for reevaluation of proposed critical intervals for the phenotypes in deletion 18q syndrome and Edwards syndrome.