Genome scan reveals several loci associated with torus palatinus.

OBJECTIVE: Torus Palatinus (TP) is a common trait with an unclear aetiology. Although prior studies suggest a hereditary component, the genetic factors that influence TP risk remain unknown. The purpose of this study is to identify genetic variants associated with TP. MATERIALS AND METHODS: We assessed the TP status of 829 individuals from various ancestral backgrounds using 3D palate scans. We then carried out a genome-wide association study (GWAS) to identify common variants associated with TP. We also performed gene-based tests across the exome to investigate the role of low-frequency coding variants. RESULTS: Our GWAS did not identify any genome-wide significant signals but identified suggestive associations including hits on chromosomes 2, 5 and 17 with p-values less than 5 × 10-6. Candidate genes at these suggestive loci have been implicated in normal-range craniofacial features, syndromes with facial and oral malformations, and bone density. We did not find evidence that low-frequency coding variants influence TP risk. In addition, we failed to replicate associations identified in prior genetic studies of TP. CONCLUSION: These findings suggest that multiple genes likely influence the development of TP. Independent replication will be required to confirm our suggestive associations.

LRP4 mutations, dental anomalies, and oral exostoses.

BACKGROUND: In order to generate a normal set of teeth, fine-tuning of Wnt/ß-catenin signaling is required, in which WNT ligands bind to their inhibitors or WNT inhibitors bind to their co-receptors. Lrp4 regulates the number of teeth and their morphology by modulating Wnt/ß-catenin signaling as a Wnt/ß-catenin activator or inhibitor, depending on its interactions with the partner proteins, such as Sostdc1 and Dkk1. AIM: To investigate genetic etiologies of dental anomalies involving LRP4 in a Thai cohort of 250 children and adults with dental anomalies. DESIGN: Oral and radiographic examinations and whole exome sequencing were performed for every patient. RESULTS: Two novel (p.Leu1356Arg and p.Ala1702Gly) and three recurrent (p.Arg263His, p.Gly1314Ser, and p.Asn1385Ser) rare variants in low-density lipoprotein receptor-related protein 4 (LRP4: MIM 604270) were identified in 11 patients. Oral exostoses were observed in five patients. CONCLUSION: Antagonism of Bmp signaling by Sostdc1 requires the presence of Lrp4. Mice lacking Lrp4 have been demonstrated to have alteration of Wnt-Bmp-Shh signaling and an abnormal number of incisors. Therefore, the LRP4 mutations found in our patients may disrupt Wnt-Bmp-Shh signaling, thereby resulting in dental anomalies and oral exostoses. Root maldevelopment in the patients suggests an important role of LRP4 in root morphogenesis.

Oral bony outgrowths: prevalence and genetic factor influence. Study of twins.

OBJECTIVE: The aim of the study was to verify the influence of a genetic factor on the etiology of oral bony outgrowths and to determine the prevalence and type of oral bony outgrowths (tori and exostoses) among a group of Lithuanian twins. MATERIALS AND METHODS: In total, 162 twins (81 twin pairs) were analyzed for the presence or absence, type, and size of oral bony outgrowths. Statistical analysis was carried out to find the prevalence of bony protuberances and the relationship between zygosity and occurrence of oral bony enlargements. Zygosity of twins was confirmed by DNA analysis. RESULTS: 59.9% of the subjects had oral bony outgrowths. Mandibular tori were found in 56.8% and palatal tori in 1.8% of the sample. Palatal exostoses and mandibular exostoses were present in 1.8% and 3.1% of the sample, respectively, whereas maxillary exostoses were not found. A higher percentage of tori and exostoses were found in the group of older subjects (>18 years old, p=0.025). No significant difference was found between men and women in the prevalence of bony outgrowths. High κ and r values (0.91±0.062) showed very good concordance of oral bony outgrowths between monozygotic and moderate concordance (0.58±0.141) between dizygotic co-twins (p<0.001). The calculation of heritability estimate verifies dominant influence of genetic factor on the etiology of oral bony outgrowths (h(2)=0.658). CONCLUSION: The most common bony outgrowth was torus mandibularis. Our results show that the genetic factor is dominant in the etiology of oral bony outgrowths.

Oral Tori Findings in an Adult Albanian Population: A Single-Center Pilot Study.

Tori are bony growths in the mouth caused by genetic and environmental factors. Oral tori may grow over time and interfere with oral hygiene, speech, mastication, and the application of dentures. The aim of this study was to evaluate the prevalence and patterns of torus mandibularis and torus palatinus according to age and gender among people in Albania. A single-center pilot study was conducted at Diamond Dental Hospital (DDH) from 1 February to 30 April 2024 in Tirana, Albania. Written consent was obtained from each participant. The patients were interviewed by one trained researcher and examined intraorally by one experienced examiner. Photographs were taken of any positive findings. The prevalence of oral tori in this sample from Albania was very high at 48%, and the peak incidence was in the 18-29 age group (54%). The most common type was torus mandibularis, with a prevalence of 39%. The most prevalent form of torus palatinus was flat (71%) and of torus mandibularis was solitary bilateral (48%). This single-center pilot study found a high prevalence of oral tori among people in Tirana, Albania. Its prevalence was not related to gender or bruxism. Dental professionals should note the high occurrence of oral tori and their importance in dental practice.

Medication-related osteonecrosis in torus palatinus: Report of a case and literature review.

BACKGROUND: Medication-related osteonecrosis of the jaw bones have been frequently reported. However, its occurrence in torus palatinus is very rare with only 10 cases published in the English-language literature. CASE REPORT: We describe an additional case in a 79-year-old woman, who was referred for evaluation of a painful swelling with areas of suppuration on the hard palate. CONCLUSION: Conservative treatment was performed and after spontaneous sequestrectomy, total healing was achieved.

Asymptomatic Symmetric Bilateral Mandibular Tori: A Case Study.

Tori are reactive or developmental localized overgrowths of alveolar bone that are not cancerous. A thin, weakly vascularized mucosa surrounds a densely cortical, low-density mass of bone marrow known as tori or exostosis. Tori are more frequently observed in middle age. Both the maxilla (torus palatinus) and the mandible (torus mandibularis) exhibit tori. Difficulty in speaking and other issues are common obstacles associated with tori. Tori range in diameter from a few millimeters to several centimeters. Surgical excision of tori is the mainstay of treatment for large tori obstructing speech, mastication, or tongue position. The following case study includes a 36-year-old male patient with an association of mandibular canine and premolar regions with bony outgrowth.

The tori of the mouth and ear: a review.

There is a great deal of literature regarding the tori of the mouth and ear. However, there is controversy regarding the etiology and prevalence of each. The torus palatinus is generally agreed to be the most common oral exostosis and is more frequently found in females. The torus mandibularis is also quite common, is more prevalent in males, and occurs bilaterally in 80% of cases. Far less data have been presented regarding the torus maxillaries primarily due to the lack of consensus regarding its nomenclature and classification. These oral tori are thought to be inherited in an autosomal dominant manner with a relatively high penetrance; however, environmental and functional factors have been postulated that may account for a more complex etiology than simply genetics. The torus auditivus is rarely acknowledged in clinical papers and most data are found in anthropological journals. Although there is an abundance of literature that addresses these traits individually, there is a lack of research that collectively acknowledges these. Therefore, the aim of this study was to present a composite review of the tori with regards to their anatomical features, prevalence, etiology and clinical relevance.

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

BACKGROUND: Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/ß-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/ß-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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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/ß-catenin-BMP-SHH signaling.

Alveolar bone exostoses following orthodontic treatment. Diagnostic considerations and clinical management.

Alveolar bone exostoses (ABE) are benign localized convex outgrowths of buccal or lingual bone, which could be delineated from the surrounding cortical plate, also known as a buttress bone formation. Our review and case series demonstrate the development of alveolar bone exostoses during orthodontic therapy. It is crucial to keep in mind that every case presented had a history of palatal tori. In our clinical observations, higher precedence of ABE development was seen in participants during incisor retraction, especially with preexisting palatal tori. Additionally, we have successfully demonstrated surgical techniques to eliminate ABE in the event that self-remission does not occur once orthodontic forces are discontinued.

LRP6 High Bone Mass Characterized in Two Generations Harboring a Unique Mutation of Low-Density Lipoprotein Receptor-Related Protein 6.

Osteoblast Wnt/ß-catenin signaling conditions skeletal development and health. Bone formation is stimulated when on the osteoblast surface a Wnt binds to low-density lipoprotein receptor-related protein 5 (LRP5) or 6 (LRP6), in turn coupled to a frizzled receptor. Sclerostin and dickkopf1 inhibit osteogenesis if either links selectively to the first ß-propeller of LRP5 or LRP6, thereby disassociating these cognate co-receptors from the frizzled receptor. Sixteen heterozygous mutations identified since 2002 within LRP5 and three heterozygous mutations identified since 2019 within LRP6 prevent this binding of sclerostin or dickkopf1 and account for the exceptionally rare, but highly instructive, autosomal dominant disorders called LRP5 and LRP6 high bone mass (HBM). Herein, we characterize LRP6 HBM in the first large affected family. Their novel heterozygous LRP6 missense mutation (c.719C>T, p.Thr240Ile) was present in two middle-aged sisters and three of their sons. They considered themselves healthy. Their broad jaw and torus palatinus developed during childhood and, contrary to the two previous reports of LRP6 HBM, the appearance of their adult dentition was unremarkable. Skeletal modeling, defined radiographically, supported classification as an endosteal hyperostosis. Areal bone mineral density (g/cm2) of the lumbar spine and total hip featured accelerated increases reaching Z-scores of ~ +8 and +6, respectively, although biochemical markers of bone formation were normal. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.

OBJECTIVE: The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families. METHODS: Oral and radiographic examinations were performed on every patient. Whole exome and Sanger sequencing were performed on DNA of the patients, the unaffected parents and unaffected siblings. LRP6 mutant proteins were modeled and analyzed. RESULTS: Five mutations in LRP6, including four missense (p.Glu72Lys, p.Lys82Asn, Tyr418His, and p.Ile773Val) and one nonsense mutation (p.Arg32Ter), were identified. These mutations have not been reported to be associated with dental anomalies or oral exostoses. Oral features included a variety of oral exostoses (7 of the 14 patients), root defects (6 of the 14 patients), and tooth agenesis (5 of the 14 patients). Less common dental anomalies included microdontia, tooth fusion, odontomas, and mesiodens. Analysis of the protein models of the five LRP6 mutations shed light on their likely impact on LRP6 protein structure and function. CONCLUSION: Fourteen patients with five LRP6 mutations, including two recurrent mutations and three novel ones, are reported. Our study shows for the first time that mutations in LRP6 are associated with mesiodens, fusion of teeth, odontomas, microdontia, long roots, molars with unseparated roots, and taurodontism.

Genome-wide family-based study in torus palatinus affected individuals.

OBJECTIVE: Tori or exostoses are bony growths that appear in different oral regions. Torus palatinus, more specifically, develop in the palate midline and can impair proper word pronunciation and hinder the fabrication and use of dentures. Even though a multifactorial inheritance model has been suggested for torus palatinus appearance, precise genetic factors involved in its etiology remain unclear. Hence, in this study we aimed to identify variants across the genome of individuals from 46 Filipino families that associate with torus palatinus. DESIGN: All families were composed of fishermen or landless rural dwellers who provided blood samples for DNA extraction and genotyping. A total of 3519 single nucleotide polymorphisms (SNPs) were analyzed through a transmission disequilibrium test in individuals affected by torus palatinus and their unaffected family members. RESULTS: Fourteen SNPs showed trends for associations to the level of p < .005 threshold and several others were nominally (p < .05) associated with torus palatinus. We highlight SNP rs6582285, which is located in the CAPS2 gene, being the C allele less transmitted than the T allele in our sample. The C allele of CAPS2 rs6582285 protects from having torus palatinus whereas the other associations found were linked to an increased risk of developing the condition. CONCLUSIONS: Trends for associations were identified for several markers across the genome, supporting the hypothesis that torus palatinus has a multifactorial mode of inheritance. We hope that our study contributes to a better understanding of torus palatinus etiology and helps guide future research in examining genes for this often-overlooked condition in different populations.

Sucrose Is Not the Whole Story: Risk Factors and Oral Health at the Contact (Yakutia, Siberia-16th/19th).

(1) Background: contact between indigenous and European populations has often resulted in changes in oral health attributed to the introduction of sucrose. Most studies are per tooth over considerable periods and with few ethnological references. (2) Aim: dental epidemiology of 96 autochthonous frozen bodies from Yakutia between the early 17th century and the late 19th century; comparisons with historical texts and ethnographic data. (3) Material and methods: we use descriptive statistics and discriminant factorial analyses to identify dominant variables in the dataset and compare periods and subjects, considering all variables. (4) Results: the peculiarities of the population are the rarity of cavities and the relative frequency of dental pathologies leading to death. Assimilation into the Russian Orthodox culture has led to decreased tooth wear and an increase in tooth loss. Dental health evolves only two centuries after the contact. (5) Conclusions: the confrontation with historical data suggests that changes are not related to the growing importance of sucrose but to a combined action: the substitution of dendrophagy by cereal flour; the decrease in immunity linked to the development of chronic infectious diseases; tobacco addiction and the mandibular torus: a risk factor promoting apical cysts.

Torus Palatinus in Taiwan Patients Receiving Peritoneal Dialysis and Hemodialysis: A Prospective Observational Study.

PURPOSE: A consensus about the pathogenesis of torus palatinus (TP) in patients receiving dialysis still eludes the scientific community. This prospective observational study investigated the epidemiology of TP in peritoneal dialysis and hemodialysis patients and analyzed the influences of multiple pathogenic factors such as mineral and bone disorders, genetic, environmental or nutritional triggers, progression of age, heredity, climatologic or biomechanical causes, and hyperparathyroidism on the formation of TP. METHODS: Between 2013 and 2016, a total of 575 chronic dialysis patients (441 on hemodialysis and 134 on peritoneal dialysis) were recruited from Chang Gung Memorial Hospital, Taiwan. Patients were stratified into two groups based on the presence (n = 179) or absence (n = 396) of TP. Demographic, oral examination, laboratory, and dialysis data were collected for analysis. Student's t-test was used to analyze the quantitative variables and Chi-square or Fisher's exact test for categorical variables. Univariate binary logistic regression analysis was conducted to determine the predictors for TP and multivariate binary logistic regression analysis to identify significant associated factors. RESULTS: The prevalence of TP in dialysis patients in this study was 31.1% (28.3% for hemodialysis and 40.3% for peritoneal dialysis). Patients with TP were younger (54.6 ± 13.4 versus 58.9 ± 14.7 years, P = 0.001) and mostly female (60.3 versus 41.2%, P < 0.001). Most TP cases (55.3%) were small in size (<2 cm), with the flat shape (56.4%) being the most common followed by the spindle (17.9%), nodular (17.3%), and lobular (8.4%) shapes. A longer duration of dialysis was associated with TP ≥2 cm than with TP <2 cm (94.4 ± 85.9 versus 72.8 ± 59.1 months, P = 0.048). Multivariate logistic regression revealed that female gender (odds ratio 2.108, 95% confidence interval 1.455-3.055, P < 0.001) and younger age (odds ratio 0.982; 95% confidence interval 0.969-0.994, P = 0.005) were significant predictors for TP. CONCLUSION: The prevalence of TP in chronic dialysis patients is 31.1%, higher in patients receiving peritoneal dialysis (40.3%) than hemodialysis (28.3%). Female gender and younger age are significant predictors associated with TP.

High bone mass from mutation of low-density lipoprotein receptor-related protein 6 (LRP6).

Wnt/ß-catenin signaling is important for skeletal development and health. Eleven heterozygous gain-of-function missense mutations within the first ß-propeller of low-density lipoprotein receptor-related protein 5 (LRP5) are known to cause the autosomal dominant disorder called high bone mass (HBM). In 2019, different heterozygous LRP6 missense mutations were identified in two American families with the HBM phenotype but including absent lateral maxillary and mandibular incisors. We report a 19-year-old Argentinian man referred for "osteopetrosis" and nine years of generalized, medium-intensity bone pain and arthralgias of both knees. His jaw and nasal bridge were broad and several teeth were missing. Routine biochemical testing, including of mineral homeostasis, was normal. Urinary deoxypyridinoline and serum CTX were slightly increased. Radiographic skeletal survey showed diffusely increased radiodensity. DXA revealed substantially elevated BMD Z-scores. Digital orthopantomography confirmed agenesis of his maxillary and mandibular lateral incisors and his second left superior premolar. Cranial magnetic resonance imaging showed diffuse thickening of the calvarium and skull base, dilation of the sheath of the optic nerves containing increased fluid and associated with subtle stenosis of the optic canal, and narrow internal auditory canals. Mutation analyses identified a heterozygous indel mutation in exon 4 of LRP6 involving a single nucleotide change and 6-nucleotide deletion (c.678T>Adel679-684, p.His226Gln-del227-228ProPhe) leading to a missense change and 2-amino acid deletion that would compromise the first ß-propeller of LRP6. Experience to date indicates LRP6 HBM is indistinguishable from LRP5 HBM without mutation analysis, although in LRP6 HBM absence of adult lateral incisors may prove to be a unique feature.

The use of torus palatinus in the identification of unknown skeletal remains.

Torus palatinus (TP) is a benign, bony outgrowth located on the hard palate. Variation in this trait occurs, ranging from absent to a protuberance several millimeters in length. If a TP becomes too large, it can interfere with daily activities and thus warrant medical attention. This case utilised the unique morphology of a TP after surgical invention to identify the unknown skeletal remains of a woman missing for six years. Even though there is still much unknown regarding the aetiology, occurrence and prevalence of TP, this study demonstrates the usefulness of anatomical variants in the identification of unknown skeletal remains.

The relationship between oral tori and bite force.

OBJECTIVE: The relationship between bite force and torus palatinus or mandibularis remains to be explained. The major aim of this study was to determine the correlation between bite force and oral tori. METHODS: The bite force of 345 patients was measured with a bite force recorder; impressions of the shape and size of the oral tori were taken on plaster models prior to orthodontic treatments. Subsequently, the relationship between oral tori and bite force was analyzed. RESULTS: The size, shape, and incidence of torus palatinus was not significantly correlated with bite force. However, the size of torus mandibularis increased significantly in proportion to the bite force (p = 0.020). The occurrence of different types of oral tori was not correlated with the bite force. DISCUSSION: The size of torus mandibularis provides information about bite force and can thus be used to clinically assess occlusal stress.

New explanation for autosomal dominant high bone mass: Mutation of low-density lipoprotein receptor-related protein 6.

LRP5 encodes low-density lipoprotein receptor-related protein 5 (LRP5). When LRP5 with a Frizzled receptor join on the surface of an osteoblast and bind a member of the Wnt family of ligands, canonical Wnt/ß-catenin signaling occurs and increases bone formation. Eleven heterozygous gain-of-function missense mutations within LRP5 are known to prevent the LRP5 inhibitory ligands sclerostin and dickkopf1 from attaching to LRP5's first ß-propeller, and thereby explain the rare autosomal dominant (AD) skeletal disorder "high bone mass" (HBM). LRP6 is a cognate co-receptor of LRP5 and similarly controls Wnt signaling in osteoblasts, yet the consequences of increased LRP6-mediated signaling remain unknown. We investigated two multi-generational American families manifesting the clinical and routine laboratory features of LRP5 HBM but without an LRP5 defect and instead carrying a heterozygous LRP6 missense mutation that would alter the first ß-propeller of LRP6. In Family 1 LRP6 c.602C>T, p.A201V was homologous to LRP5 HBM mutation c.641C>T, p.A214V, and in Family 2 LRP6 c.553A>C, p.N185H was homologous to LRP5 HBM mutation c.593A>G, p.N198S but predicting a different residue at the identical amino acid position. In both families the LRP6 mutation co-segregated with striking generalized osteosclerosis and hyperostosis. Clinical features shared by the seven LRP6 HBM family members and ten LRP5 HBM patients included a broad jaw, torus palatinus, teeth encased in bone and, reportedly, resistance to fracturing and inability to float in water. For both HBM disorders, all affected individuals were taller than average for Americans (Ps < 0.005), but with similar mean height Z-scores (P = 0.7606) and indistinguishable radiographic skeletal features. Absence of adult maxillary lateral incisors was reported by some LRP6 HBM individuals. In contrast, our 16 patients with AD osteopetrosis [i.e., Albers-Schönberg disease (A-SD)] had an unremarkable mean height Z-score (P = 0.9401) lower than for either HBM group (Ps < 0.05). DXA mean BMD Z-scores in LRP6 HBM versus LRP5 HBM were somewhat higher at the lumbar spine (+7.8 vs +6.5, respectively; P = 0.0403), but no different at the total hip (+7.9 vs +7.7, respectively; P = 0.7905). Among the three diagnostic groups, only the LRP6 HBM DXA BMD values at the spine seemed to increase with subject age (R = +0.7183, P = 0.0448). Total hip BMD Z-scores were not significantly different among the three disorders (Ps > 0.05), and showed no age effect (Ps > 0.1). HR-pQCT available only for LRP6 HBM revealed indistinct corticomedullary boundaries, high distal forearm and tibial total volumetric BMD, and finite element analysis predicted marked fracture resistance. Hence, we have discovered mutations of LRP6 that cause a dento-osseous disorder indistinguishable without mutation analysis from LRP5 HBM. LRP6 HBM seems associated with generally good health, providing some reassurance for the development of anabolic treatments aimed to enhance LRP5/LRP6-mediated osteogenesis.

Is it as dangerous as it looks?

A common bony protrusion that occurs over the hard palate is sometimes mistaken for a malignancy especially when it is large. This bony growth is a torus palatinus (TP), which is a benign bony prominence over the hard palate. It occurs most commonly in bilateral multiple form, and is often located at the canine to premolar area. A basic knowledge of the assessment and management of TP is important, particularly for the first-line family physician to ensure that the correct information is given to the patient.