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Key Points Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP affects approximately 1 in 700 live births, with wide variability across geographic origin, racial and ethnic groups, as well as environmental exposures and socioeconomic status. CLP can occur in syndromic or non-syndromic forms. This Review focuses on the latter. Although twin studies and familial clustering studies have provided compelling evidence for a genetic component to non-syndromic CLP, few pedigrees show clear-cut Mendelian inheritance and many cases appear to be sporadic. Accurate phenotyping is crucial to understanding both the epidemiology and aetiology of any congenital malformation because the power to detect effects is weakened when heterogeneous groups are treated as a single entity. To date, genetic approaches to non-syndromic CLP have included: linkage analysis using large, multiplex families or smaller but inbred families, or analysis of affected relative pairs; association studies using case–parent trios or case–control samples; identification of chromosomal anomalies or micro-deletions in cases; and direct sequencing of affected individuals. Genome-wide association studies have provided recent major advances in our understanding of genes and pathways that have a role in the aetiology of CLP. There is remarkable heterogeneity by ancestry in the relative contributions by genes found with common variants contributing to CLP. There is evidence that environmental factors have a role in CLP risk and interactions of the environment with certain genetic variants have been identified. The next critical phase of statistical analyses will be to examine the heterogeneity underlying the aetiology of oral clefts and to investigate the gene–gene and gene–environment interactions that control risk. Integration of genetic and environmental risk using epigenetics, systems biology, gene expression and epidemiology will be required to generate a synthesis that will both better characterize aetiologies and eventually lead to improvements in prevention and clinical care. Clefts of the lip and/or palate are common and have a complex genetic and environmental basis. Recent work on these birth defects illustrates the value of combining genome-wide association studies, animal models and improved clinical phenotyping. Future work may also address gene–environment interactions. Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.

Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10–15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA 1c reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management.

Clefts of the lip and palate are generally divided into two groups, isolated cleft palate and cleft lip with or without cleft palate, representing a heterogeneous group of disorders affecting the lips and oral cavity. These defects arise in about 1·7 per 1000 liveborn babies, with ethnic and geographic variation. Effects on speech, hearing, appearance, and psychology can lead to longlasting adverse outcomes for health and social integration. Typically, children with these disorders need multidisciplinary care from birth to adulthood and have higher morbidity and mortality throughout life than do unaffected individuals. This Seminar describes embryological developmental processes, epidemiology, known environmental and genetic risk factors, and their interaction. Although access to care has increased in recent years, especially in developing countries, quality of care still varies substantially. Prevention is the ultimate objective for clefts of the lip and palate, and a prerequisite of this aim is to elucidate causes of the disorders. Technological advances and international collaborations have yielded some successes.

Objectives. We examined school days missed for routine dental care versus dental pain or infection to determine the relationship between children's oral health status and school attendance and performance. Methods. We used 2008 data from the North Carolina Child Health Assessment and Monitoring Program. The study sample, weighted to reflect the state's population, included 2183 schoolchildren. Variables assessed included school absences and performance, oral health status, parental education, health insurance coverage, race, and gender. Results. Children with poor oral health status were nearly 3 times more likely (odds ratio = 3.89; 95% confidence interval = 1.96, 7.75) than were their counterparts to miss school as a result of dental pain. Absences caused by pain were associated with poorer school performance (P < .05), but absences for routine care were not. Mediation analyses revealed that oral health status was associated with performance independent of absence for pain. Conclusions. Children with poorer oral health status were more likely to experience dental pain, miss school, and perform poorly in school. These findings suggest that improving children's oral health status may be a vehicle to enhancing their educational experience.

Elisabeth Mangold and colleagues report a genome-wide meta-analyses of non-syndromic cleft lip with or without cleft palate (NSCL/P). They report six new genetic loci associated with risk for NSCL/P. We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; P NSCLP = 6.51 × 10 −11 ; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84–3.16).

Information about the long-term clinical survival of large amalgam and composite restorations is still lacking. This retrospective study compares the longevity of three- and four-/five-surface amalgam and composite restorations relative to patients’ caries risk. Patient records from a general practice were used for data collection. We evaluated 1949 large class II restorations (1202 amalgam/747 composite). Dates of placement, replacement, and failure were recorded, and caries risk of patients was assessed. Survival was calculated from Kaplan-Meier statistics. After 12 years, 293 amalgam and 114 composite restorations had failed. Large composite restorations showed a higher survival in the combined population and in the low-risk group. For three-surface restorations in high-risk patients, amalgam showed better survival.

This review discusses the most common forms of temporomandibular disorders: myofascial pain disorder, intra-articular disk derangement disorders, osteoarthritis, and rheumatoid arthritis. Current views on its pathogenesis and presentation and recommended diagnostic studies and treatment approaches are discussed. This review discusses the most common forms of temporomandibular disorders. Current views on its pathogenesis and presentation and recommended diagnostic studies and treatment approaches are discussed. The temporomandibular joint (TMJ) may be affected by inflammatory, traumatic, infectious, congenital, developmental, and neoplastic diseases, as seen in other joints. However, the most common affliction of the TMJ and masticatory apparatus is a group of functional disorders with associated pain that occurs predominantly in women and was previously known as the TMJ pain dysfunction syndrome. Since 1978, there have been substantial changes in the study of etiologic factors, pathophysiology, diagnosis, and management of what are now called temporomandibular disorders. 1 , 2 The general perception that all symptoms in the head, face, and jaw region without an identifiable cause constitute a . . .

Terri Beaty and colleagues report a genome-wide association study of cleft lip with/without cleft palate. They identified variants near MAFB and ABCA4 associated with risk of this birth defect in case-parent trios of European and Asian ancestry. Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate ( MAFB , most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635–0.778, P = 1.44 × 10 −11 ; and ABCA4 , most significant SNP rs560426, with OR = 1.432, 95% CI 1.292–1.587, P = 5.01 × 10 −12 ) and two previously identified regions (at chromosome 8q24 and IRF6 ) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4 . Expression studies support a role for MAFB in palatal development.

BACKGROUND Periodontal disease is common among adults in the US and is a potential source of chronic inflammation. Recent data have suggested an important role for chronic inflammation in the development of coronary heart disease (CHD). OBJECTIVE To aid the United States Preventive Services Task Force (USPSTF) in evaluating whether periodontal disease is an independent novel risk factor for incident CHD. METHODS Studies were identified by searching Medline (1966 through March 2008) and reviewing prior systematic reviews, reference lists, and consulting experts. Prospective cohort studies that assessed periodontal disease, Framingham risk factors, and coronary heart disease incidence in the general adult population without known CHD were reviewed and quality rated using criteria developed by the USPSTF. Meta-analysis of good and fair quality studies was conducted to determine summary estimates of the risk of CHD events associated with various categories of periodontal disease. RESULTS We identified seven articles of good or fair quality from seven cohorts. Several studies found periodontal disease to be independently associated with increased risk of CHD. Summary relative risk estimates for different categories of periodontal disease (including periodontitis, tooth loss, gingivitis, and bone loss) ranged from 1.24 (95% CI 1.01–1.51) to 1.34 (95% CI 1.10–1.63). Risk estimates were similar in subgroup analyses by gender, outcome, study quality, and method of periodontal disease assessment. CONCLUSION Periodontal disease is a risk factor or marker for CHD that is independent of traditional CHD risk factors, including socioeconomic status. Further research in this important area of public health is warranted.

Elisabeth Mangold and colleagues report a genome-wide association study for non-syndromic cleft lip with or without cleft palate. We conducted a genome-wide association study for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in 401 affected individuals and 1,323 controls, with replication in an independent sample of 793 NSCL/P triads. We report two new loci associated with NSCL/P at 17q22 (rs227731, combined P = 1.07 × 10 −8 , relative risk in homozygotes = 1.84, 95% CI 1.34–2.53) and 10q25.3 (rs7078160, combined P = 1.92 × 10 −8 , relative risk in homozygotes = 2.17, 95% CI 1.32–3.56).