Oral parafunction and bruxism in Rett syndrome and associated factors: An observational study.

OBJECTIVES: To explore patterns of parafunction, and bruxism, and its relationships with genotype and snoring in individuals with Rett syndrome (RTT). METHODS: Retrospective observational data of those with confirmed MECP2 mutations in the InterRett database (n = 216) were used to investigate experience of parafunctional habits, and bruxism and their relationships with genotype and snoring using multivariable linear regression. RESULTS: The prevalence of parafunction was 98.2%. Bruxism was reported (66.2%) with the patterns mostly both diurnal and nocturnal (44.1%) and exclusively diurnal (42.7%). Compared to individuals with C-terminal deletion, individuals with p.Arg106Trp mutations were less likely to have bruxism reported (aOR = 0.15; 95% CI 0.02-0.98, p = 0.05) and those with p.Arg168* mutation were more likely to have frequent bruxism than none or occasional bruxism reported (aROR 3.4; 95% CI 1.1-10.7 p = 0.04). The relative odds of having nocturnal bruxism constantly, compared to none/occasionally, were higher among those 'always' snoring (aROR 6.24; 95% CI 2.1-18.2, p = 0.001) than those with no snoring. CONCLUSIONS: There appeared to be genotypic association with bruxism in p.Arg168* and p.Arg106Trp mutations and association between nocturnal bruxism and frequent snoring in an international sample of individuals with RTT. Clinical significance of the high prevalence of bruxism should be highlighted in relation to difficulty communicating pain and increased dental treatment need in RTT.

Association between genetic polymorphisms in the melatonin receptor type 1 A gene and sleep bruxism.

OBJECTIVE: This study evaluated whether single nucleotide polymorphisms in the melatonin receptor type 1 A gene are associated with sleep bruxism in a Brazilian population. DESIGN: Individuals with suspected sleep-related problems were evaluated using polysomnography, following the recommendations proposed by the American Academy of Sleep Medicine and the Research Diagnostic Criteria for Temporomandibular Disorders. Deoxyribonucleic acid (DNA) samples were collected, and three single nucleotide polymorphisms in the melatonin receptor type 1 A gene (rs13140012, rs6553010, and rs6847693) were selected and genotyped using real-time polymerase chain reaction (RT-PCR). Chi-square and odds ratio tests were used to analyze genotypes and alleles individually, while using the plink software for haplotypes. A confidence interval of 95% was considered, and statistical significance was set at p < 0.05. RESULTS: This study included 48 individuals aged between 21 and 80 years, with 27 males and 21 females. From this sample, 17 individuals were diagnosed with sleep bruxism and 31 without bruxism. No associations were found between sleep bruxism and single nucleotide polymorphisms in either the genotypic, allelic, dominant, or recessive models (p > 0.05). Haplotype genetic analysis also did not reveal any association between single nucleotide polymorphisms and sleep bruxism (p > 0.05). CONCLUSION: The genetic polymorphisms rs6553010, rs13140012, and rs6847693 were not associated with sleep bruxism in the studied population.

Polymorphisms of the serotonin receptors genes in patients with bruxism: a systematic review.

This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are associated with bruxism etiology. METHODOLOGY: This systematic review was registered in PROSPERO (CRD42018094561). A search was conducted for articles published in or before May 2021. To qualify for eligibility in this review, the studies had to be case-controls, cohort or cross-sectional. The inclusion criteria were the articles with a group of patients with bruxism and a control group in which the presence of these SNPs was evaluated. The exclusion criteria were the investigations of other polymorphisms, the studies that did not consider a control group for comparison, case reports, and reviews. The NOS and JBI were used to evaluate the methodological quality of studies. RESULTS: We conducted this study with databases, such as Web of Science, Scopus, Embase, PubMed/MEDLINE, and ProQuest. We considered four studies eligible. A total of 672 participants were included,187 with sleep bruxism, 105 with awake bruxism, 89 with sleep and awake bruxism, and 291 controls. One study found a strong association between the SNPs rs6313, rs2770304 and rs4941573 of the 5-HT2A receptor gene and sleep bruxism. In one study, we considered the C allele of the SNP rs2770304 a risk factor for sleep bruxism. We found no significant results of other SNPs in sleep bruxers compared to controls. We found no positive association concerning the SNPs and groups of awake bruxism and sleep and awake bruxism. CONCLUSION: The different results regarding the SNPs in sleep bruxers could be explained by the genetic distinction between Chilean, Mexican, Japanese, and Polish population. More clinical trials and prospective studies must be conducted with larger sample size and in different ethnicities to confirm the results of this review.

Is there an association of genetic polymorphisms of the catechol-O-methyltransferase gene (rs165656 and rs174675) and the 5-hydroxytryptamine receptor 2A gene (rs4941573 and rs6313) with sleep bruxism in individuals with obstructive sleep apnea?

OBJECTIVE: To evaluate the association of single-nucleotide polymorphisms within the catechol-O-methyltransferase and 5-hydroxytryptamine receptor 2A genes with sleep bruxism in individuals diagnosed with obstructive sleep apnea. DESIGN: Sixty-nine individuals with suspected sleep-related problems were evaluated by polysomnography, following the recommendations of the American Academy of Sleep Medicine. Deoxyribonucleic acid (DNA) samples were collected only from 48 of the study participants because of missing polysomnographic data. DNA samples were collected and two single-nucleotide polymorphisms in the 5-hydroxytryptamine receptor 2A encoding HTR2A gene (rs4941573 and rs6313) and two in the catechol-O-methyltransferase gene (rs165656 and rs174675) were selected to be genotyped using real-time polymerase chain reaction. The association between sleep bruxism and genetic polymorphisms was investigated by recessive and dominant models. Association analyses were performed using a 95% confidence interval and the level of statistical significance was p < 0.05. RESULTS: From the 69 study participants, 48 were included in the polymorphism analysis and sleep bruxism was present in 35.4%. No significant differences were observed in the dominant and recessive models (p > 0.05). Haplotype and diplotype analyses revealed the predicted four haplotypes and two diplotypes were not associated with sleep bruxism. CONCLUSION: Polymorphisms rs174675 and rs165656 in the catechol-O-methyltransferase gene and rs4941573 and rs6313 in the 5-hydroxytryptamine receptor 2A gene were not significantly associated with sleep bruxism in individuals with obstructive sleep apnea.

Breathing problems, being an only child and having parents with possible sleep bruxism are associated with probable sleep bruxism in preschoolers: a population-based study.

PURPOSE: To determine the prevalence of probable sleep bruxism (SB) in preschoolers and associated factors. METHODS: A cross-sectional, population-based study was carried out with 862 dyads of parents/preschoolers aged 5 from Teresina, Brazil. Data collection was performed through a questionnaire answered by parents/guardians about socioeconomic, demographic, and health condition data. Each child was examined for diagnosis of probable SB based on the presence of dental wear associated or not with the report of teeth grinding by parents/guardians. The analysis of independent variables was stratified into four levels of determinants: demographic characteristics of the child (distal), characteristics of the family, environmental factors (intermediate), and health conditions (proximal). Descriptive analysis and bivariate and multivariate Poisson's regression were performed using a hierarchical approach (p < 0.05). RESULTS: The prevalence of probable SB was 36%. In the final adjusted multivariate hierarchical model, a preschooler who was the only child (PR = 1.25; 95%CI = 1.02-1.51), with breathing problems (PR = 1.43; 95%CI = 1.19-1.73), and having parents/guardians with possible sleep bruxism (PR = 1.65; 95%CI = 1.32-2.07) had a higher prevalence of probable SB. CONCLUSION: The prevalence of probable SB in preschoolers was high and associated with the condition of being an only child, the presence of breathing problems, and having parents/guardians with possible sleep bruxism.

Polymorphisms of the serotonin receptors genes in patients with bruxism: a systematic review

Abstract This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are associated with bruxism etiology. Methodology This systematic review was registered in PROSPERO (CRD42018094561). A search was conducted for articles published in or before May 2021. To qualify for eligibility in this review, the studies had to be case-controls, cohort or cross-sectional. The inclusion criteria were the articles with a group of patients with bruxism and a control group in which the presence of these SNPs was evaluated. The exclusion criteria were the investigations of other polymorphisms, the studies that did not consider a control group for comparison, case reports, and reviews. The NOS and JBI were used to evaluate the methodological quality of studies. Results We conducted this study with databases, such as Web of Science, Scopus, Embase, PubMed/MEDLINE, and ProQuest. We considered four studies eligible. A total of 672 participants were included,187 with sleep bruxism, 105 with awake bruxism, 89 with sleep and awake bruxism, and 291 controls. One study found a strong association between the SNPs rs6313, rs2770304 and rs4941573 of the 5-HT2A receptor gene and sleep bruxism. In one study, we considered the C allele of the SNP rs2770304 a risk factor for sleep bruxism. We found no significant results of other SNPs in sleep bruxers compared to controls. We found no positive association concerning the SNPs and groups of awake bruxism and sleep and awake bruxism. Conclusion The different results regarding the SNPs in sleep bruxers could be explained by the genetic distinction between Chilean, Mexican, Japanese, and Polish population. More clinical trials and prospective studies must be conducted with larger sample size and in different ethnicities to confirm the results of this review.

Genetic basis of sleep bruxism and sleep apnea-response to a medical puzzle.

Sleep bruxism (SB) and obstructive sleep apnea (OSA) are co-occurring sleep conditions. The study aimed to evaluate the association of selected single-nucleotide polymorphisms (SNPs) occurring within the genes of the serotonin and dopamine pathways in SB and OSA and investigate the relationship between them. The study group included 100 Caucasian patients. SB and OSA were diagnosed in 74 and 28 patients, respectively. In addition, 125 unrelated Caucasian healthy blood donors served as randomly selected controls to enable comparison of polymorphisms. The following SNPs were analyzed: rs2770304 and rs6313 within the serotonin receptor encoding gene (HTR2A), rs4680 polymorphism of the catechol-O-methyltransferase (COMT) gene, and rs686 within the dopamine receptor (DRD1) encoding gene. The prevalence of the DRD1 rs686 G variant (GG homozygosity) was found to be high in the study group compared to the control group. Bruxism episode index (BEI) was found to be significantly increased in the HTR2A rs6313 TT homozygotes compared to the heterozygous patients. Moreover, within a group of the HTR2A rs2770304 TT homozygous cases, a statistically significant correlation was observed between BEI and apnea-hypopnea index. These results indicate that DRD1 rs686 may potentially affect predisposition to SB, that HTR2A rs6313 SNP may be involved in SB pathogenesis, and that HTR2A rs2770304 polymorphism might contribute to the association between SB and OSA. This suggests a possible genetic contribution to the etiology of primary SB.

DNA is hypomethylated in circadian manifestations of bruxism.

OBJECTIVE: The aim of this study was to compare the global DNA methylation levels in patients under bruxism treatment and a control group. METHODS: Subjects undergoing bruxism treatment were classified in awake bruxism (42 patients), sleep bruxism (32 patients) and both conditions (42 patients). The control group included 42 individuals. A colorimetric assay (MethylFlash Methylated DNA 5-mC Quantification Kit, Epigenetic Group Inc., NY, USA) was used to determine the global DNA methylation levels. RESULTS: Statistically significant differences were found in amounts of methylated DNA in all circadian manifestations of bruxism compared with a control group (sleep bruxism = 0.95% ± 2.02%; awake bruxism = 0.87% ± 2.1%; sleep and awake bruxism = 0.17% ± 0.25%; Control = 1.69% ± 1.6%; Kruskal-Wallis test [p = .0001] followed by Dunn's test [p < .05]). CONCLUSION: Patients undergoing bruxism treatment exhibited hypomethylated DNA levels when compared to control group. Our results suggest that DNA hypomethylation might be a novel aetiologic factor in bruxism aetiology. Further researches must be performed exploring the role of epigenetics modifications in circadian manifestations of bruxism.

Single nucleotide polymorphisms in genes of dopaminergic pathways are associated with bruxism.

OBJECTIVES: This research aimed to evaluate the frequency of single nucleotide polymorphisms (SNPs) in dopaminergic pathway genes (DRD1, DRD2, DRD3, DRD4, DRD5, and MAOB) in patients undergoing bruxism treatment and controls. SUBJECTS AND METHODS: Patients submitted to bruxism treatment were classified in awake bruxism (61 patients), sleep bruxism (26 patients), and awake-sleep bruxism (43 patients). Control group included 59 patients. Association between circadian manifestations of bruxism and SNPs was investigated using Fisher's exact test, chi-squared test, and calculating the odds ratios and their respective 95% confidence intervals. RESULTS: The G allele of DRD2 rs1800497 SNP was associated with a significant risk reduction of awake-sleep bruxism (p = 0.041), while the C allele of DRD3 rs6280 SNP was associated with increased risk of sleep bruxism (p = 0.02), and the C allele of DRD5 rs6283 SNP was associated with decreased risk of awake bruxism (p = 0.01). CONCLUSIONS: To our knowledge, this is the first report exploring the contribution of genetic variants in dopaminergic pathways to bruxism development, considering all circadian manifestations. Our findings indicate a possible genetic influence in the etiology of awake, sleep, and awake-sleep bruxism. Therefore, further research is needed to increase the current understanding of bruxism physiopathology.

Evaluation of genetic factors involved in nocturnal electromyographic activity of masticatory muscles in twins.

OBJECTIVES: The objectives of this study were to assess sleep bruxism events by directly recording electromyographic activity during sleep and to reveal the relative importance of genetic and environmental factors involved in sleep bruxism in twins. MATERIAL AND METHODS: The subjects consisted of 108 twins (mean age 22.2 ± 6.4 years). Electromyographic activity of temporalis muscles during sleep was evaluated using a portable automatic sleep bruxism analyzer (Grindcare 3.0, Medotech A/S), and recordings were carried out for at least three consecutive nights. Quantitative genetic statistics based on structural equation modeling was utilized to estimate variance components. RESULTS: Monozygotic twin-pair correlation for the number of nocturnal electromyographic activities recorded in this study (r = 0.463, P = 0.009) was higher than dizygotic twin-pair correlation (r = 0.103, P = 0.725). The proportion of total phenotypic variance in the liability of sleep bruxism to attribute to genetic influences, related to the electromyographic activities, was 48 % (95 % CI 17-95 %) and to unique environmental influences was 52 % (95 % CI 28-82 %). CONCLUSIONS: Additive genetic effects may be a contributing factor to the occurrence of nocturnal EMG activity associated with sleep bruxism. CLINICAL RELEVANCE: A greater understanding of the contribution of genetic factors could have beneficial uses, including enhanced accuracy of sleep bruxism diagnosis, management of sleep bruxism, and enhanced estimation of the prognosis for patients suffering from sleep bruxism. In addition, it could be also important to adequately evaluate the environmental factors in patients with sleep bruxism.

Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism.

PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4.25-fold increased risk of SB. Based on this finding, the aim of this study was to generate of neural cells using SB patient-specific induced pluripotent stem cells (iPSCs). METHODS: Two SB patients with C/C genotype of rs6313 and two controls with T/T genotype were screened by laboratory-based polysomnographic recordings and the TaqMan genotyping assay. Four lines of iPSCs, two from SB patients and two from controls, were established from peripheral blood mononuclear cells by introduction of reprogramming factors. We performed quality control assays on iPSCs using expression of markers for undifferentiated pluripotent cells, immunostaining for pluripotency markers, a three-germ layer assay, and karyotype analysis. The established iPSCs were differentiated into neurons using the neurosphere culture system. 5-HT2A gene expression in these neurons was evaluated by quantitative real-time PCR. RESULTS: Patient-specific iPSCs were successfully differentiated into neurons expressing 5-HT2A. CONCLUSIONS: This report is the first successful generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism, which has the potential to elucidate the etiology and underlying mechanism of SB.

Epigenetics and Bruxism: Possible Role of Epigenetics in the Etiology of Bruxism.

Bruxism is defined as a repetitive jaw muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. There are two distinct circadian phenotypes for bruxism: sleep bruxism (SB) and awake bruxism, which are considered separate entities due to the putative difference in their etiology and phenotypic variance. The detailed etiology of bruxism so far remains unknown. Recent theories suggest the central regulation of certain pathophysiological or psychological pathways. Current proposed causes of bruxism appear to be a combination of genetic and environmental (G×E) factors, with epigenetics providing a robust framework for investigating G×E interactions, and their involvement in bruxism makes it a suitable candidate for epigenetic research. Both types of bruxism are associated with certain epigenetically determined disorders, such as Rett syndrome (RTT), Prader-Willi syndrome (PWS), and Angelman syndrome (AS), and these associations suggest a mechanistic link between epigenetic deregulation and bruxism. The present article reviews the possible role of epigenetic mechanisms in the etiology of both types of bruxism based on the epigenetic pathways involved in the pathophysiology of RTT, PWS, and AS, and on other epigenetic disruptions associated with risk factors for bruxism, including sleep disorders, altered stress response, and psychopathology.

Bruxism and genetics: a review of the literature.

People who suffer from bruxism (teeth-grinding) often ask their dentists whether their condition is hereditary. The purpose of this study is to enable dentists to provide an 'evidence-based' answer to this question. The biomedical literature was searched using PubMed, and 32 publications were identified, of which nine proved relevant to the research question. The references cited by the publications identified yielded one further publication, bringing the total number of publications included in the analysis to 10. Four publications related to family studies, five related to twin studies and one related to a DNA analysis. With the exception of one of the twin studies, all the included studies concluded that bruxism appears to be (in part) genetically determined. Dentists whose patients ask them about bruxism can therefore tell them that teeth-grinding does indeed 'run in families'.

Genetic factors account for half of the phenotypic variance in liability to sleep-related bruxism in young adults: a nationwide Finnish twin cohort study.

OBJECTIVES: The aim of the present study was to examine the role of genetic and environmental factors in the phenotypic variance of bruxism in a large population-based cohort of young adult twins in Finland. METHODS: The material of the present study derives from the FinnTwin16 cohort study consisting of five birth cohorts of twin pairs born in 1975-1979 who completed a questionnaire (at mean age 24, range 23-27 years) with data on frequency of sleep-related bruxism in 2000-2002. We used quantitative genetic modeling, based on the genetic similarity of monozygotic and dizygotic twins, to estimate the most probable genetic model for bruxism, based on decomposition of phenotypic variance into components:additive genetic effects (A), dominant genetic effects (D), and non-shared environmental effects (E). RESULTS: On average, 8.7% experienced bruxism weekly, 23.4% rarely, and 67.9% never, with no significant gender difference (p = .052). The best fitting genetic model for bruxism was the AE-model. Additive genetic effects accounted for 52% (95% Cl 0.41--0.62) of the total phenotypic variance. Sex-limitation model revealed no gender differences. CONCLUSIONS: Genetic factors account for a substantial proportion of the phenotypic variation of the liability to sleep-related bruxism, with no gender difference in its genetic architecture.

Association of genetic, psychological and behavioral factors with sleep bruxism in a Japanese population.

Sleep bruxism is a sleep-related movement disorder that can be responsible for various pains and dysfunctions in the orofacial region. The aim of the current case-control association study was to investigate the association of genetic, psychological and behavioral factors with sleep bruxism in a Japanese population. Non-related participants were recruited and divided into either a sleep bruxism group (n = 66) or control group (n = 48) by clinical diagnoses and 3-night masseter electromyographic recordings by means of a portable miniature device. The Epworth Sleepiness Scale, Temperament and Character Inventory, NEO-Five Factor Inventory and custom-made questionnaires that asked about familial aggregation, alcohol intake, caffeine intake, cigarette smoking, past stressful life events, daytime tooth-contacting habit, temporomandibular disorder, daily headache, snoring, apnea/hypopnea symptoms, leg-restlessness symptoms and nocturnal-myoclonus symptoms were administered. In addition, 13 polymorphisms in four genes related to serotonergic neurotransmission (SLC6A4, HTR1A, HTR2A and HTR2C) were genotyped. These factors were compared between case (sleep bruxism) and control groups in order to select potential predictors of sleep-bruxism status. The statistical procedure selected five predictors: Epworth Sleepiness Scale, leg-restlessness symptoms, rs6313 genotypes, rs2770304 genotypes and rs4941573 genotypes. A multivariate stepwise logistic regression analysis between the selected predictors and sleep-bruxism status was then conducted. This analysis revealed that only the C allele carrier of HTR2A single nucleotide polymorphism rs6313 (102C>T) was associated significantly with an increased risk of sleep bruxism (odds ratio = 4.250, 95% confidence interval: 1.599-11.297, P = 0.004).This finding suggests a possible genetic contribution to the etiology of sleep bruxism.

Familial nocturnal facio-mandibular myoclonus mimicking sleep bruxism.

A mother and son presented with a multi-decade history of nocturnal tongue biting and bleeding. In both patients, video polysomnographic recordings documented bursts of electromyographic activity originating in the masseter and spreading to orbicularis oris and oculi muscles, present only during sleep. Faciomandibular myoclonic activity during sleep mimics sleep bruxism and may be familial.

Parasomnias: co-occurrence and genetics.

In clinical practice, parasomnias are often found to run in families and to co-occur. Several studies have indicated a role of genetic factors in them. In 1990, a questionnaire (response rate, 77%) sent to the Finnish Twin Cohort, a representative population sample aged 33-60 years, surveyed the frequency of five parasomnias (sleepwalking, sleeptalking, enuresis, bruxism, and nightmares) in childhood and as adults. In assessing the phenotypic covariation and shared genetic effects between the parasomnias, we used polychoric correlations and structural equation modelling. In childhood (n = 5856 individuals), co-occurrence is highest in sleeptalking with sleepwalking (R = 0.73), nightmares (R = 0.50), and bruxism (R = 0.43). As adults (n = 8567), the results are similar (R = 0.56, 0.43, and 0.39, respectively). The analyses of shared genetic effects included 815 monozygotic and 1442 dizygotic twin pairs with complete responses on four parasomnias as adults. The strongest genetic covariation was found in sleeptalking with sleepwalking, sleeptalking with bruxism, and in sleeptalking with nightmares. The estimated proportions of shared genetic effects were 50, 30, and 26%, respectively. The present results indicate that parasomnias share some common genetic background.