An improved diagnostic method for taurodontism and a comparative study on its effectiveness evaluation.

OBJECTIVE: The two commonly used diagnostic methods for taurodontism are susceptible to aging changes, mastication wear and other factors. Therefore, this study proposed an improved diagnostic method for taurodontism, and compared it with the previous two methods as a supplement for taurodontism diagnosis. METHODS: The included patients were aged 10-89 years and admitted to the Department of Stomatology of Hebei Eye Hospital from June 1, 2022 to May 31, 2023. Eighty cone-beam computed tomography images were divided equally into 4 groups: 10-29, 30-49, 50-69, and 70-89 years old. The right mandibular first molars were selected as measurement objects. Firstly, |BD| and taurodontism index (TI)-related parameters were measured using Shifman and Chanannel's method and crown-body(CB) and root (R) lengths was measured by Seow and Lai's method. The improved method used the length from the cementoenamel junction(CEJ) to the root bifurcation point(body, B)and the root length(root, R)as the measurement objects. Finally, TI, CB/R ratios, and B/R ratios were calculated according to the formulas given below. One-way ANOVA analysis was mainly used to compare the differences in the values, indices and ratios of taurodontism among different age groups (p<0.05). RESULTS: With the increase of age, |BD| and TI values decreased significantly (p<0.01). The CB/R ratios of 70-89 years group were significantly lower than those of the other three groups (p<0.01). Ratios derived from the improved method were significantly lower in the 70-89 years than in 10-29 years group (p<0.05). CONCLUSIONS: The |BD| and TI parameters proposed by Shifman and channel are significantly influenced by age. The measurements of Seow and Lai (CB/R ratios) were less affected by age compared with those of the former. The improved method(B/R ratios) was least affected by age, which would reduce error and bias in the measurement of taurodontism and obtain more objective results in older patients.

Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis.

Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.

Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies.

KCTD1 plays crucial roles in regulating both the SHH and WNT/ß-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in KCTD1 might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies. Whole exome sequencing identified two unrelated families with rare (p.Arg241Gln) or novel (p.Pro243Ser) variants in KCTD1. The variants segregated with the dental anomalies in all nine patients from the two families. Clinical findings of the patients included taurodontism, unseparated roots, long roots, tooth agenesis, a supernumerary tooth, torus palatinus, and torus mandibularis. The role of Kctd1 in root development is supported by our immunohistochemical study showing high expression of Kctd1 in Hertwig epithelial root sheath. The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. Functional studies on the p.Arg241Gln variant are consistent with an impact on ß-catenin levels and canonical WNT signaling. This is the first report of the association of KCTD1 variants and isolated dental anomalies.

Olfactory bulb anomalies in KBG syndrome mouse model and patients.

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.

Radiological features and treatment of erupting maxillary canines in relation to the occurrence of dental developmental abnormalities.

OBJECTIVE: This study aimed to investigate the radiological features of the permanent canines and the treatment carried out to ensure their eruption relative to certain features involved in Dental Anomaly Patterns (DAP). MATERIAL AND METHODS: The cross-sectional part of this retrospective register--based study focused on 1,315 dental panoramic tomographs (DPTs) of children aged 8.5-10.5 years, while the longitudinal part involved information on the treatment provided for 1,269 canines after the DPTs and on their eruption into the oral cavity. RESULTS: The canines of the DAP children more often showed evidence of early treatment (p = 0.014), with girls having more frequently interceptive treatment (p = 0.004) and boys early headgear (p = 0.022). Delayed dental age was associated with early treatment (OR 3.29, 95% CI 1.08-9.99). Either no or clear overlapping of a canine with the lateral incisor occurred more often in the DAP children, whereas canine inclination did not differ between the groups. The root development stage of the canine was more often either beginning or well advanced in the DAP children. CONCLUSIONS: The children with dental developmental abnormalities more often showed evidence of early treatment for the canines. Monitoring of the erupting canines after the first mixed stage is important to enable timely early treatment.

"Examining the link between tooth agenesis and papillary thyroid cancer: is there a risk factor?" Observational study.

BACKGROUND: Mutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease. MATERIALS AND METHODS: This case-control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20-40 with PTC, as well as 424 females in the control group who were of similar age. RESULTS: The prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC. CONCLUSION: Our study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.

Clinical analysis of nonsyndromic oligodontia phenotypes.

OBJECTIVES: To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. METHODS: The information of 178 patients with oligodontia was collected, including histories, oral examinations, and panoramic radiographs. Tooth agenesis characteristics were calculated and evaluated. All the data were statistically analyzed with SPSS 24.0 software. RESULTS: No significant difference in the number of missing teeth was found between sexes nor between the right and left sides, and congenitally missing teeth affected the maxillary arch (P<0.05). The highest prevalence of tooth agenesis was observed in the mandibular second premolars. In the maxillary arch, the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars. The agenesis of the bilateral second premolars was observed in the mandibular arch. The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular antagonistic quadrants. Approximately 16.85% of patients with nonsyndromic oligodontia were affected by other tooth-related anomalies. CONCLUSIONS: The common patterns of tooth agenesis were successfully identified in patients with nonsyndromic oligodontia. Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Systemic and oral abnormalities in Kabuki syndrome: a case series.

OBJECTIVE: This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. STUDY DESIGN: Clinical examination was conducted on 15 individuals to investigate orodental alterations such as tooth abnormalities and cleft lip and/or palate, and the patient records were also reviewed to investigate systemic diseases such as cardiopathies, infectious and immunologic diseases, nephropathies, and delayed neuropsychomotor development. RESULTS: All individuals with KS presented cleft lip and/or palate, 11 (73.34%) tooth abnormalities, 5 (33.34%) congenital cardiopathies, 12 (80%) infectious or immunologic diseases, 1 (6.67%) nephropathy, and 14 (93.34%) had an intellectual disability. CONCLUSION: Individuals with KS often have dental anomalies such as hypodontia, cleft or palate, and systemic disorders such as congenital heart disease and infectious diseases. Intellectual disability is present in most cases. These alterations should be investigated as early as possible to prevent the increase in morbidity in these individuals.

Developmental and Acquired Abnormalities of the Teeth.

This review aims to present a detailed analysis of the most common developmental and acquired dental abnormalities, including caries, resorptive lesions, and congenital anomalies of teeth number, size, form, and structure. This review highlights how diagnostic imaging can aid in the accurate identification and management of these conditions.

Dentofacial manifestations of a Paediatric patient with Goltz-Gorlin Syndrome.

Goltz-Gorlin syndrome is a rare X-linked inherited disorder associated with PORCN (porcupine homolog-Drosophila) gene mutation. It primarily affects the skin and its appendages. The characteristic cutaneous features include a blaschko-linear pattern, skin atrophy, pigmentary changes, and telangiectasia. The oral manifestations have been reported in more than half of the affected individuals. The most common oral findings include enamel hypoplasia, hypodontia, supernumerary teeth, microdontia, vertical grooving of the teeth, taurodontism, fusion, and abnormal root morphology reported in sporadic cases. The objective of this case report is to describe the dentofacial characteristics of a middle childhood aged girl with Goltz-Gorlin syndrome.

Single variant, yet "double trouble": TSC and KBG syndrome because of a large de novo inversion.

Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests including TSC1 and TSC2 Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints in TSC2 and ANKRD11, which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome. Our findings illustrate how complex variants, such as large inversions, may be missed by clinical tests and further highlight the importance of well-defined clinical diagnoses in uncovering complex molecular mechanisms of a disease, such as complex variants and "double trouble" effects.

The Rogdi knockout mouse is a model for Kohlschütter-Tönz syndrome.

Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and amelogenesis imperfecta. Here, we present a novel Rogdi mutant mouse deleting exons 6-11- a mutation found in KTS patients disabling ROGDI function. This Rogdi-/- mutant model recapitulates most KTS symptoms. Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility. Spontaneous locomotion and circadian activity tests demonstrate Rogdi mutant hyperactivity mirroring patient spasticity. Object recognition impairment indicates memory deficits. Rogdi-/- mutant enamel was markedly less mature. Scanning electron microscopy confirmed its hypomineralized/hypomature crystallization, as well as its low mineral content. Transcriptomic RNA sequencing of postnatal day 5 lower incisors showed downregulated enamel matrix proteins Enam, Amelx, and Ambn. Enamel crystallization appears highly pH-dependent, cycling between an acidic and neutral pH during enamel maturation. Rogdi-/- teeth exhibit no signs of cyclic dental acidification. Additionally, expression changes in Wdr72, Slc9a3r2, and Atp6v0c were identified as potential contributors to these tooth acidification abnormalities. These proteins interact through the acidifying V-ATPase complex. Here, we present the Rogdi-/- mutant as a novel model to partially decipher KTS pathophysiology. Rogdi-/- mutant defects in acidification might explain the unusual combination of enamel and rare neurological disease symptoms.

Prevalence and Distribution of Dental Anomalies in Schoolchildren in Kuwait.

OBJECTIVE: Dental anomalies (DA) can affect paediatric patients' aesthetics, function, and psychological well-being. There is a lack of data about the prevalence of DA in children in Kuwait. This study aimed to investigate the prevalence and distribution of DA amongst schoolchildren aged 8 to 12 years. METHODS: A retrospective study was conducted using panoramic digital radiographs of children who attended a single dental center. All radiographs were evaluated by 2 calibrated and trained examiners. RESULTS: DA were present in 110 (20.1%) out of the 546 panoramic radiographs examined: 53.6% in females and 46.4% in males. The mean age of children with DA (9.83 ± 1.29) was similar to that of children with no anomalies (9.96 ± 1.46). The most prevalent anomaly was dental agenesis (9.3%), followed by taurodontism (6.6%) and ectopic eruption (EE, 2%). DA were more common in the maxilla (58.2%) compared to the mandible (41.8%, P = .042). Congenitally missing teeth were significantly more frequent in the mandible (56.9%) than in the maxilla (43.1%, P = .003). EE was significantly more common in the maxilla (90.9%) than in the mandible (9.1%, P = .024). Microdontia and root dilacerations were only present in males, whilst supernumerary teeth, transposition, and impacted teeth were noted in females only. CONCLUSIONS: The prevalence of DA amongst schoolchildren in Kuwait was considered to be relatively high. Certain DA were associated with gender. The significant prevalence of DA highlights the need for early diagnosis using panoramic radiographs, particularly during the ages of 9 and 10, in order to ensure effective patient management.

Peripheral odontogenic fibroma in a child with Ellis-van Creveld syndrome: Case report.

INTRODUCTION: Ellis-van Creveld (EVC) syndrome is an autosomal recessive disorder predominantly characterized by a disproportionate dwarfism, ectodermal dysplasia, postaxial polydactyly, and congenital heart malformations and pulmonary hypoplasia. OBJECTIVE: In this article, we hereby present a case of a 6-year-old Brazilian boy with EVC syndrome who presented a rare oral lesion as well as a remarkable number of classical and uncommon oral and dental features. CASE REPORT: Clinical and radiographic examination revealed multiple enamel hypoplasia, teeth agenesis, conical teeth, lower canine rotation, bilateral posterior crossbite, taurodontism of deciduous and permanent molars and delayed tooth eruption, dental caries, and absent vestibular sulcus. Additionally, a whitish lobulated nodule located in the alveolar ridge in the anterior region of the mandible was noted. Anatomopathological examination was compatible with the diagnosis of peripheral odontogenic fibroma (POF). In a 10-month clinical follow-up, no signs of recurrence were observed. CONCLUSION: In view of the characteristic oral findings of EVC syndrome and the potential for recurrence of POF, the pediatric dentist plays an essential role in clinical follow-up, planning and preventive, and rehabilitative treatment.

Ocular manifestations in a cohort of 43 patients with KBG syndrome.

Ophthalmological conditions are underreported in patients with KBG syndrome, which is classically described as presenting with dental, developmental, intellectual, skeletal, and craniofacial abnormalities. This study analyzed the prevalence of four ophthalmological conditions (strabismus, astigmatism, myopia, hyperopia) in 43 patients with KBG syndrome carrying variants in ANKRD11 or deletions in 16q24.3 and compared it to the literature. Forty-three patients were recruited via self-referral or a private Facebook group hosted by the KBG Foundation, with 40 of them having pathogenic or likely pathogenic variants. Virtual interviews were conducted to collect a comprehensive medical history verified by medical records. From these records, data analysis was performed to calculate the prevalence of ophthalmological conditions. Out of the 40 participants with pathogenic or likely pathogenic variants, strabismus was reported in 9 (22.5%) participants, while astigmatism, myopia, and hyperopia were reported in 11 (27.5%), 6 (15.0%), and 8 (20.0%) participants, respectively. Other reported conditions include anisometropia, amblyopia, and nystagmus. When compared to the literature, the prevalence of strabismus and refractive errors is higher than other studies. However, more research is needed to determine if variants in ANKRD11 play a role in abnormal development of the visual system. In patients with established KBG syndrome, screening for misalignment or refractive errors should be done, as interventions in patients with these conditions can improve functioning and quality of life.

Oral manifestations of nine individuals with Williams syndrome. A case series.

AIMS: Williams syndrome (WS) is a congenital developmental disorder characterized, mainly, by distinctive facial features, cardiovascular anomalies, growth delay and a typical neurobehavioral profile. The oral manifestations have not been sufficiently described and, therefore, the aim of the current study was to present the clinical, radiographic and microbiological findings of individuals with WS. METHODS AND RESULTS: A series of nine WS individuals (seven females) with mean age 21 years-old were evaluated. A complete intraoral clinical examination, a radiographic analysis using panoramic and cephalometric x-ray and a supra- and sub-gingival microbiological profiling were performed. We observed abnormal tooth morphology, excessive interdental spacing, congenitally missing permanent teeth and malocclusion. High levels of DMFT were observed and gingivitis was present in all subjects. Bacteria related to periodontal disease were detected in dental plaque. Three patients were classified with a gingival phenotype type I according to the Maynard and Wilson classification. The sella turcica bridging was a novel finding for this group of patients. CONCLUSION: Due to the elevated prevalence of gingivitis, caries and malocclusion, a multidisciplinary approach including dental follow-ups should be the standard of care in WS patients.