Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions. OBJECTIVE: Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context. METHODS: The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank. RESULTS: We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10-6), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10-6), NLRP3 rs2056795 (P = 8.91 × 10-6) and MAP2K4 rs7225328 (P = 1.64 × 10-5). CONCLUSION: This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.

Restricted tongue mobility and ankyloglossia in 6-8-year-old Vietnamese school children: prevalence and association with tongue strength and endurance.

PURPOSE: Generating adequate tongue pressure against the hard palate requires full-range mobility of the tongue. The study aimed to (1) determine the prevalence of restricted tongue mobility and ankyloglossia and (2) determine whether, in children with restricted tongue mobility, their condition also affects tongue pressure. METHODS: A cross-sectional study of healthy 6-8-year-old children from primary schools in central Vietnam was conducted in 2019. Restricted tongue mobility and ankyloglossia were graded using the tongue range of motion ratio (TRMR), with the tongue-tip-to-incisive papillae (TIP) for the anterior tongue tip and lingual-palatal suction (LPS) for the posterior two-thirds of the tongue. Tongue strength and tongue endurance were measured by the Iowa Oral Pressure Instrument. Statistical analysis investigated the associations between tongue mobility and tongue pressure measurement. RESULTS: Five hundred twelve children (46.5% female, mean age 7.2 ± 0.2 years) were assessed. The prevalence of anterior ankyloglossia and restricted mobility was 17.5%, with 16.2% cases of less than 50% mobility and 1.3% cases of less than 25% mobility. The prevalence of posterior ankyloglossia and restricted mobility with less than 30% mobility was 28.9%. Anterior restricted mobility was not a predictor of reduced tongue pressure. Posterior restricted mobility in LPS was independently associated with tongue strength but not tongue endurance. CONCLUSION: Restrictions of posterior tongue mobility in ankyloglossia are more frequent than restrictions in anterior tongue mobility. Reduced tongue strength is related to mobility and the severity of restrictions in the posterior tongue. These findings suggest that restricted posterior tongue mobility may affect tongue muscle weakness.

Association of Temporomandibular Joint Osseous Changes with Anxiety, Depression, and Limitation of Mandibular Function in Elderly Vietnamese.

OBJECTIVES: This study aimed (1) to determine the prevalence of anxiety, depression, and TMJ osseous changes in elderly Vietnamese according to sex and residence, and (2) to investigate the association of temporomandibular joint (TMJ) osseous changes with anxiety, depression, and limitation of mandibular function. METHODS: Elderly people living in Danang, Vietnam were recruited. Participants were screened for anxiety and depression using the self-reported 7-item Generalized Anxiety Disorder Scale (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9), respectively. Participants then self-rated the limitation of their mandibular function using the 20-item Jaw Functional Limitation Scale (JFLS-20) questionnaire. TMJ osseous changes (erosion, flattening, osteophytes, and sclerosis) were evaluated using digital orthopantomography. RESULTS: Of 179 participants aged 65 to 74 years, 17.9% and 35.8% had anxiety and depression symptoms, respectively. Compared with urban residents, rural residents had higher prevalence of anxiety (23.3% vs 12.4%, p = 0.009) and depression (46.62% vs 24.7%, p = 0.019). The prevalence of TMJ osseous changes was 58.1%. The most common TMJ osseous change was flattening (41.3%), followed by erosion (34.6%), sclerosis (16.2%), and osteophytes (7.8%). Participants with or without TMJ osseous changes were comparable in terms of GAD-7 score, PHQ-9 score, and JFLS-20 score and sub-scores. CONCLUSIONS: Anxiety and depression and TMJ osseous changes were prevalent in elderly Vietnamese. Rural residents had higher prevalence of anxiety and depression than urban residents. TMJ osseous changes were not associated with anxiety, depression, or limitation of mandibular function.

A missense mutation in DUSP6 is associated with Class III malocclusion.

Class III malocclusion is a common dentofacial phenotype with a variable prevalence according to ethnic background. The etiology of Class III malocclusion has been attributed mainly to interactions between susceptibility genes and environmental factors during the morphogenesis of the mandible and maxilla. Class III malocclusion shows familial recurrence, and family-based studies support a predominance of an autosomal-dominant mode of inheritance. We performed whole-exome sequencing on five siblings from an Estonian family affected by Class III malocclusion. We identified a rare heterozygous missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene, a likely causal variant. This variant co-segregated with the disease following an autosomal-dominant mode of inheritance with incomplete penetrance. Transcriptional activation of DUSP6 has been presumed to be regulated by FGF/FGFR and MAPK/ERK signaling during fundamental processes at early stages of skeletal development. Several candidate genes within a linkage region on chromosome 12q22-q23--harboring DUSP6--are implicated in the regulation of maxillary or mandibular growth. The current study reinforces that the 12q22-q23 region is biologically relevant to craniofacial development and may be genetically linked to the Class III malocclusion.

Non-syndromic tooth agenesis associated with a nonsense mutation in ectodysplasin-A (EDA).

Mutations in the ectodysplasin-A (EDA) gene have been generally associated with X-linked hypohidrotic ectodermal dysplasia (XLHED). Recently, missense mutations in EDA have been reported to cause familial non-syndromic tooth agenesis. In this study, we report a novel EDA mutation in an Estonian family segregating non-syndromic tooth agenesis with variable expressivity. Affected individuals had no associated defects in other ectodermal organs. Using whole-exome sequencing, we identified a heterozygous nonsense mutation c.874G>T (p.Glu292X) in the TNF homology domain of EDA in all affected female patients. This protein-altering variant arose de novo, and the potentially causative allele was transmitted to affected offspring from the affected mother. We suggest that the dental phenotype variability described in heterozygous female carriers of EDA mutation may occur because of the differential pattern of X-chromosome inactivation, which retains reduced levels of EDA-receptor signaling in tissues involved in tooth morphogenesis. This results in selective tooth agenesis rather than XLHED phenotype. The present study broadens the mutation spectrum for this locus and demonstrates that EDA mutations may result in non-syndromic tooth agenesis in heterozygous females.