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ABSTRACT: Objectives: Metabolic syndrome (MetS) has been suggested to play a role in congenital defects. This study investigated the association of MetS and its components with orofacial clefts (OFCs). Methods: We conducted a case-control study in Northeast Thailand. Ninety-four cases with cleft lip, with or without cleft palate, were frequency matched with 94 controls on the infant's age and mother's education. We administered a mother's health questionnaire and collected anthropometric measurements and blood samples. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed among infants without a family history of OFCs, mothers who were not currently breastfeeding, and mothers who were >6 months postpartum. Results: When compared to mothers of normal weight, the OR associated with OFCs were 2.44 (95% CI, 1.04-5.76, P = .04) in overweight mothers, and 3.30 (95% CI, 1.14-9.57, P = .03) in obese mothers. Low HDL-C raised the risk of OFCs 2.95 times (95% CI, 1.41-6.14, P = .004) compared to normal HDL-C levels. Mothers with 4 or 5 features of MetS were 2.77 times as likely to have the affected child than those who did not (95% CI, 0.43-17.76), but this difference was not statistically significant (P = .28). Subgroup analyses showed similar results, uncovering an additional significant association between underweight mothers and OFCs. Conclusions: The results indicate a robust association between underweight and overweight/obese maternal body mass index and increased OFC risk. Additionally, low HDL-C in mothers is linked to an elevated risk of OFCs. Further research is needed to evaluate if promoting strategies to maintain optimal body weight and enhance HDL-C levels in reproductive-age and pregnant women icould contribute to a reduction of the risk of OFCs in their progeny.

Congenital cleft of the secondary palate occurs when there is failure of one or both maxillary processes to fuse with the nasal septum during embryonic development. Palatal cleft severity can range from a simple focal fissure of the caudal soft palate to full-thickness defects of varied widths involving the entire soft and hard palate. A novel staged medially positioned single mucoperiosteal flap technique in 4 canine patients is reported. This flap technique is based on the major palatine and infraorbital arteries with strategic extractions of maxillary teeth and placement of allograft membrane in 3 of 4 cases for treatment of clefts wider than may be repaired effectively by traditional methods. [ABSTRACT FROM AUTHOR]

Children with isolated cleft of the lip and/or palate (iCL/P) have been shown to be at risk for impaired reading ability. Structural and functional neuroimaging studies have revealed subtle morphological and functional abnormalities correlated to cognition and reading ability. However, the integrity of white matter tracts and their potential relationship to reading performance in iCL/P is under-studied. The purpose of the present study was to evaluate white matter integrity related to cognition and reading skills among participants with and without iCL/P. Data from two cross-sectional, case/control studies with similar neuropsychological batteries and diffusion tensor imaging (DTI) protocols were combined. The final sample included 210 participants (ages 7 to 27 years). Group and sex differences in fractional anisotropy (FA) values were examined between participants with (n = 105) and without (n = 105) iCL/P. Potential associations between FA values and age, cognition, and reading skills were also evaluated separately by group and sex. Sex effects were prominent in association and projection fibers, and effects of cleft status were found in association fibers and cerebellar regions, with isolated associations to reading skills. Findings provide preliminary understanding of microstructural associations to cognitive and reading performance among children, adolescents, and young adults with iCL/P. [ABSTRACT FROM AUTHOR]

Abstract Background Nonsyndromic orofacial clefts (NSOC) are the craniofacial most common congenital malformations. There are evidences that the nonsyndromic cleft palate (NSCP) development differs from other NSOC. However, most of the publications treat NSCP without considering that information. Furthermore, few studies focus on NSCP. The aim of this study was to describe epidemiological findings of patients with isolated NSCP in Brazil. Methods In this cross-sectional multicenter study, four reference Centers for treatment in three different Brazilian states was investigated. Data were obtained from clinical records of patients, between November 2021 and June 2022. Researched variables were sociodemographic, clinical characteristics and pregnancy and family history. Pearson’s chi-square and ANOVA One-way tests were used for associations. Results Majority were female (58.1%), white (60.7%) with incomplete NSCP (61.2%). There was an association between complete NSCP and a positive history of medical problems during pregnancy (p = 0.016; 27.9%; OR: 1.94; 1.12–3.35). Systemic alterations were perceived in 40.6% of the sample with odds ratio for development of the complete type (OR: 1.21; 0.74–1.97). Higher OR was visualized in medication use during pregnancy (OR: 1.35; 0.76–2.37) and positive family history of oral cleft (OR: 1.44; 0.80–2.55). Dental and surgical care was associated with higher age groups (p

Oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are the most common types of congenital anomalies of the human face. Various genetic and environmental factors play a role in developing oral clefts. Several studies have shown the association of the PAX7 gene and the 8q24 region with these oral clefts in different populations worldwide. However, there are no reported studies on the possible connection between the PAX7 gene and the 8q24 region nucleotide variants and the risk of developing nonsyndromic oral clefts (NSOC) in the Indian population. Hence, this study aimed to test the possible association between PAX7 gene single-nucleotide polymorphisms (SNPs) rs880810, rs545793,rs80094639, and rs13251901 of the 8q24 region using a case-parent trio design. Forty case-parent trios were selected from the CLP center. Genomic DNA was isolated from the cases and their parents. The rs880810, rs545793, rs80094639, and rs13251901 were genotyped by the MassARRAY technique. PLINK software was used for statistical analysis. All the SNPs were tested for Hardy-Weinberg equilibrium. No statistical significance was found with any SNPs, as none of the genotyped SNPs showed a p-value of less than 0.05. Hence, the rs880810, rs545793, and rs80094639 of the PAX7 gene, and rs13251901 of the 8q24 region are not associated with NSOC in the Indian population.

Background: Nonsyndromic orofacial clefts (NSOC) are the craniofacial most common congenital malformations. There are evidences that the nonsyndromic cleft palate (NSCP) development differs from other NSOC. However, most of the publications treat NSCP without considering that information. Furthermore, few studies focus on NSCP. The aim of this study was to describe epidemiological findings of patients with isolated NSCP in Brazil. Methods: In this cross-sectional multicenter study, four reference Centers for treatment in three different Brazilian states was investigated. Data were obtained from clinical records of patients, between November 2021 and June 2022. Researched variables were sociodemographic, clinical characteristics and pregnancy and family history. Pearson's chi-square and ANOVA One-way tests were used for associations. Results: Majority were female (58.1%), white (60.7%) with incomplete NSCP (61.2%). There was an association between complete NSCP and a positive history of medical problems during pregnancy (p = 0.016; 27.9%; OR: 1.94; 1.12–3.35). Systemic alterations were perceived in 40.6% of the sample with odds ratio for development of the complete type (OR: 1.21; 0.74–1.97). Higher OR was visualized in medication use during pregnancy (OR: 1.35; 0.76–2.37) and positive family history of oral cleft (OR: 1.44; 0.80–2.55). Dental and surgical care was associated with higher age groups (p < 0.050). Conclusions: NSCP was most prevalent in white skin color female. Complete NSCP is associated with medical problems during pregnancy. Medication use during pregnancy and positive family history of oral cleft increase the chance of developing complete NSCP. [ABSTRACT FROM AUTHOR]

Purpose: The US Food and Drug Administration established the Sentinel System to monitor the safety of medical products. A component of this system includes parameterizable analytic tools to identify mother‐infant pairs and evaluate infant outcomes to enable the routine monitoring of the utilization and safety of drugs used in pregnancy. We assessed the feasibility of using the data and tools in the Sentinel System by assessing a known association between topiramate use during pregnancy and oral clefts in the infant. Methods: We identified mother‐infant pairs using the mother‐infant linkage table from six data partners contributing to the Sentinel Distributed Database from January 1, 2000, to September 30, 2015. We compared mother‐infant pairs with first‐trimester exposure to topiramate to mother‐infant pairs that were topiramate‐unexposed or lamotrigine‐exposed and used a validated algorithm to identify oral clefts in the infant. We estimated adjusted risk ratios through propensity score stratification. Results: There were 2007 topiramate‐exposed and 1 066 086 unexposed mother‐infant pairs in the main comparison. In the active‐comparator analysis, there were 1996 topiramate‐exposed and 2859 lamotrigine‐exposed mother‐infant pairs. After propensity score stratification, the odds ratio for oral clefts was 2.92 (95% CI: 1.43, 5.93) comparing the topiramate‐exposed to unexposed groups and 2.72 (95% CI: 0.75, 9.93) comparing the topiramate‐exposed to lamotrigine‐exposed groups. Conclusions: We found an increased risk of oral clefts after topiramate exposure in the first trimester in the Sentinel database. These results are similar to prior published observational study results and demonstrate the ability of Sentinel's data and analytic tools to assess medical product safety in cohorts of mother‐infant pairs in a timely manner. [ABSTRACT FROM AUTHOR]

Objective: This study examines the effects of state facial surgery mandates on the timeliness of primary cleft repair surgery for privately insured children with oral clefts in the United States. Materials and Methods: Using IBM Health MarketScan® Database from 2001 to 2017, we estimate regression models separately for age at cleft lip repair and cleft palate repair by having a mandate while considering child‐level factors and other state differences. The sample includes 1,451 children who had primary cleft lip repair by age 12 months, and 1,402 children who had primary cleft palate repair by age 18 months. Results: A mandate was associated with earlier cleft lip repair by 13 days (95% CI, −21.5 to −4.7 days) when controlling for state differences, regardless if the child had other birth defects. For children needing cleft palate repair, a mandate was associated with earlier surgery by 87 days (95% CI, −136.1 to −38.4 days) only when no other birth defects were present. Conclusions: State facial surgery mandates were associated with earlier cleft lip repair for children with or without other birth defects, and earlier cleft palate repair for children without other birth defects (besides oral clefts). Findings suggest benefits to privately insured children with oral clefts from state mandates to cover needed services. [ABSTRACT FROM AUTHOR]

Oral clefts (OCs) are frequently co‐occurring with other non‐OC congenital anomalies. The types and the prevalence of anomalies co‐occurring with OCs vary in the reported studies. The aims of this report were to study the types and the prevalence of the anomalies co‐occurring with OCs in a well‐defined population. The types and the prevalence of anomalies co‐occurring in cases with OCs were ascertained in all terminations of pregnancy, stillbirths, and live births in 387,067 births occurring consecutively during the period 1979–2007 in the area covered by our registry of congenital anomalies which is population based, 789 cases of OCs were registered during the study period with a prevalence of 20.4 per 10,000 births, 39.5% of the cases had associated non‐OC anomalies. Associated anomalies were more common in cases with cleft palate (52.4%) than in cases with cleft lip and palate (37.3%) and in cases with cleft lip only (16.8%). Chromosomal abnormalities were present in 94 (11.9%) cases including 27 trisomies 13, 15 trisomies 18, 12 22 q11.2 deletion, and 40 other chromosomal abnormalities. Nonchromosomal recognizable conditions were diagnosed in 38 cases (4.8%) including syndromes, associations, spectrums and sequences. Multiple congenital anomalies (MCAs) were present in 180 cases (22.8%). The most frequent MCA were in the musculoskeletal system (16.7%), the central nervous system (15.0%), the urogenital system (13.7%), the cardiovascular system (8.6%), and the digestive system (6.6%). The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with OCs. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to determine the association between nonsyndromic oral clefts (OC) in children and ABO, Rh blood groups, lip, and dermatoglyphic patterns of their unaffected parents. Methods: This case–control study was conducted at a tertiary cleft center in Chennai, India, among 240 individuals comprising 80 units (40 cases and controls, respectively). Each unit (triad) was constituted by a child (0–12 years of age) either born with nonsyndromic OC (cases) or with no diagnosed congenital anomaly (control) and their unaffected parents (mother and father). ABO and Rh blood groups, specific lip print, fingerprint pattern, and palmar asymmetry were recorded for each individual. Strength of association of related factors was assessed by multivariable logistic regression reported as adjusted odds ratios and 95% confidence interval. Results: A1-positive blood group was found to be considerably higher among case mothers (14.39 [1.57–32.27]). A higher odds of OCs were observed among case mothers with whorl lip pattern (1.51 [1.16–3.17]) and radial loop pattern in fingers (1.44 [1.09–2.31]) relative to controls. In addition, palmar asymmetry was distinctively higher among case parents compared to controls (P < 0.01). Conclusion: Findings indicate that A1-positive blood group, higher frequency of whorl lip, and radial loop finger patterns in mothers and higher ulnar loop pattern in fathers and palmar asymmetry in both parents increases odds of occurrence of OC among their offspring. These identifiable traits offer potential scope for better service planning among resource-constrained disadvantaged communities in India.

There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO2) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO2 concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO2 and the risk of OCs during the exposure windows. Maternal SO2 exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15–1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO2 exposure and the risk of OCs. Future studies are now required to verify the association between SO2 exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prevalence of nonsyndromic oral clefts in twins compared to singletons in the United States and to evaluate the association between birth weight and nonsyndromic oral clefts. Design: A large population-based cross-sectional study was performed using the data from the US National Center for Health Statistics database in 2017. Participants: Our sample consisted of 128 310 twins and 3 723 273 singletons. Methods: The variables collected were sociodemographic variables, environmental predictors, and clinical measures. Descriptive analysis, bivariate, and multivariate logistic regression were performed. Main Outcome Measure: The main outcome variable in our study is nonsyndromic oral clefts. Results: The prevalence of nonsyndromic oral clefts was 5.22 per 10 000 in twins and 5.12 per 10 000 in singletons. Results show no significant risk of nonsyndromic oral clefts in twins compared to singletons (P =.92). There was a significant relationship between birth weight and infant diagnosed with nonsyndromic oral clefts (P =.01). Unadjusted odds ratio for birth weight was 2.52 (95% CI: 2.25-2.82). Adjusted odds for potential confounders such as mother's age, race, mother's education, gender of the infant, APGAR 5-minute score, gestational age, prenatal smoking, number of prenatal care visits, and mother's body mass index were resulted in similar but with a slightly lower odds of 2.11 (95% CI: 1.78-2.50). Conclusion: Compared to singletons, twins did not have higher risk of nonsyndromic oral clefts. Infants with low birth weight were more prone to have nonsyndromic oral clefts. [ABSTRACT FROM AUTHOR]

Two large studies of case–parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene–environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case–parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case–parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for CASP9 on 1p36 located about 3 Mb from PAX7, a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in MUSK on 9q31.3 from meta-analysis. Markers near SLCO3A1 also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near RETREG1 (a.k.a. FAM134B) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case–parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC.

Objective: The objective of the study is to determine the association between nonsyndromic oral clefts (OC) in children and ABO, Rh blood groups, lip, and dermatoglyphic patterns of their unaffected parents.Methods: This case-control study was conducted at a tertiary cleft center in Chennai, India, among 240 individuals comprising 80 units (40 cases and controls, respectively). Each unit (triad) was constituted by a child (0-12 years of age) either born with nonsyndromic OC (cases) or with no diagnosed congenital anomaly (control) and their unaffected parents (mother and father). ABO and Rh blood groups, specific lip print, fingerprint pattern, and palmar asymmetry were recorded for each individual. Strength of association of related factors was assessed by multivariable logistic regression reported as adjusted odds ratios and 95% confidence interval.Results: A1-positive blood group was found to be considerably higher among case mothers (14.39 [1.57-32.27]). A higher odds of OCs were observed among case mothers with whorl lip pattern (1.51 [1.16-3.17]) and radial loop pattern in fingers (1.44 [1.09-2.31]) relative to controls. In addition, palmar asymmetry was distinctively higher among case parents compared to controls (P < 0.01).Conclusion: Findings indicate that A1-positive blood group, higher frequency of whorl lip, and radial loop finger patterns in mothers and higher ulnar loop pattern in fathers and palmar asymmetry in both parents increases odds of occurrence of OC among their offspring. These identifiable traits offer potential scope for better service planning among resource-constrained disadvantaged communities in India. [ABSTRACT FROM AUTHOR]

Objectives: I plan to review the types of defects caused by gestational hyperthermia. Hyperthermia‐induced malformations in animals and humans involve many organs and structures, particularly the central nervous system, as well as other defects. The type of defect is related to the timing of the hyperthermic insult, and the underlying mechanisms include cell death, membrane disruption, vascular disruption, and placental infarction. Methods: Review of recent epidemiologic studies (2005–2020) has confirmed an association between gestational hyperthermia and birth defects. Results: There are strong associations between neural tube defects and maternal fever, and other studies have demonstrated associations between first trimester hyperthermia and an increased risk for cardiovascular defects, oral clefts, isolated congenital ear defects, cataracts, hypospadias, renal anomalies, possibly anorectal malformations, and congenital anomalies in general, suggesting that this association between maternal hyperthermia and birth defects in humans is causal. The first prospective evaluation of maternal fever was reported in 1998, and this study confirmed findings from previous case‐control studies and case series regarding the magnitude and duration of elevated maternal body temperature in relation to an increased risk for neural tube defects as well as a specific pattern of malformation. Conclusions: The consistency of findings across these different study designs supports the causal nature of the relationship between maternal fever and specific birth defects. This review summarizes the recent human evidence documenting the gestational effects of maternal hyperthermia. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of cleft palate is challenging. Numerous 2-dimensional and 3-dimensional methods have been proposed to assess the integrity of the fetal palate, yet detection rates remain relatively low. We propose the "Hard Palate Sweep," a novel 2-dimensional method that enables clear demonstration of the entire fetal palate throughout pregnancy, in a single sweep, avoiding acoustic shadows cast by surrounding bones. This study aimed to assess the feasibility and performance of the Hard Palate Sweep, performed throughout pregnancy. This was a prospective cross-sectional study performed between 2018 and 2022 in pregnant patients referred for a routine or targeted anomaly scan between 13 and 40 weeks of gestation. The presence or absence of a cleft palate was determined using the "Hard Palate Sweep." This was compared with the postnatal palate integrity assessment. Test feasibility and performance indices, including sensitivity, specificity, and positive and negative predictive values were calculated. Offline clips were reviewed by 2 investigators for the assessment of inter- and intraoperator agreement, using Cohen's kappa formula. The study protocol was approved by the institutional ethics committee. All participating patients were informed and provided consent. A total of 676 fetuses were included in the study. The Hard Palate Sweep was successfully performed in all cases, and 19 cases were determined to have a cleft palate. Of these, 13 cases were excluded because postmortem confirmation was not performed, leaving 663 cases available for analysis. Six cases determined to have a cleft palate were confirmed postnatally. In 655 of 657 cases prenatally determined to have an intact palate, this was confirmed postnatally. In the 2 remaining cases, rare forms of cleft palate were diagnosed postnatally, rendering 75% sensitivity, 100% specificity, 100% positive predictive value, and 99.7% negative predictive value for the Hard Palate Sweep (P <.001). There was complete intra- and interoperator agreement (kappa=1; P <.0001). The Hard Palate Sweep is a feasible and accurate method for prenatally detecting a cleft palate. It was successfully performed in all attempted cases between 13 and 40 weeks of gestation. This method is reproducible, offering high sensitivity and specificity. Implemented routinely, the Hard Palate Sweep is expected to increase the prenatal detection of cleft palate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the occurrence of nonsyndromic cleft lip and/or palate (NSCL/P) in families of patients with prostate cancer (PC). Study design: We conducted a case-control study involving a total of 748 individuals, 280 of which had PC, and 468 were free-cancer healthy individuals. The patients answered a questionnaire with basic demographic information and family history of NSCL/P in first-degree relatives. The information collected was stored in a database and analyzed by using the statistical program SPSS® 24.0 for Windows (Chicago, IL, USA). In order to determine the association with NSCL/P, chi-square and Fisher’s exact test and odds ratio (OR) with its 95% confidence interval (95% CI) for risk magnitude assessment. Values with p

The craniofacial complex develops mainly in the first trimester of pregnancy, but its final shaping and the development of the teeth extend into the second and third trimesters. It is intimately connected with the development of the brain because of the crucial role the cranial neural crest cells play and the fact that many signals which control craniofacial development originate in the brain and vice versa. As a result, malformations of one organ may affect the development of the other. Similarly, there are developmental connections between the craniofacial complex and the teeth. Craniofacial anomalies are either isolated, resulting from abnormal development of the first two embryonic pharyngeal arches, or part of multiple malformation syndromes affecting many other organs. They may stem from gene mutations, chromosomal aberrations or from environmental causes induced by teratogens. The craniofacial morphologic changes are generally cosmetic, but they often interfere with important functions such as chewing, swallowing and respiration. In addition, they may cause hearing or visual impairment. In this review we discussed only a small number of craniofacial malformations and barely touched upon related anomalies of dentition. Following a brief description of the craniofacial development, we discussed oral clefts, craniofacial microsomia, teratogens that may interfere with craniofacial development resulting in different malformations, the genetically determined craniosynostoses syndromes and few other relatively common syndromes that, in addition to the craniofacial complex, also affect other organs. The understanding of these malformations is important in dentistry as dentists play an integral role in their diagnosis and multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

Objective: Non‐syndromic cleft lip, with or without cleft palate (NSCL/P), is a common craniofacial birth defect, the risk of which is influenced from multiple genetic loci. Association study outcomes between single nucleotide polymorphisms (SNPs) near the muscle segment homeobox gene 1 (MSX1) and NSCL/P have been inconsistent. This compels a meta‐analysis to obtain more precise estimates. Methods: From 15 publications, we examined 12 SNPs under six groups (SG), based on linkage disequilibrium. Pooled odds ratios and 95% confidence intervals were calculated under the standard genetic models. The pooled effects were subjected to subgroup, outlier, sensitivity, and funnel plot (publication bias) analyses. Results: Three of the six SGs showed significant associations. SG1 and SG4 effects indicated reduced risks. SG1 outcomes were attributed to outlier treatment, which the Asian outcomes validated. In contrast, increased risks were observed in SG3. All these significant outcomes were deemed robust by sensitivity analysis with no evidence of publication bias. Conclusions: Our study shows eight MSX1 SNPs associated with risk of NSCL/P. SG1 and SG4 carriers are protected (up to 23%), but SG3 carriers are 1.3‐fold susceptible. Outlier treatment unmasked the significant associations in SG1. Non‐heterogeneity and robustness helped elevate the level of evidence in our significant findings. [ABSTRACT FROM AUTHOR]

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Genetic variants causing syndromic orofacial clefts can also contribute to the etiology of NSCL/P. The purpose of the present study was to explore gene–gene (G × G) interaction using common single nucleotide polymorphic (SNP) markers in fibroblast growth factor (FGF) family and its receptors and T‐box genes, which were associated with syndromic orofacial clefts. Our study was conducted in 806 Chinese NSCL/P case‐parent trios drawn from an international consortium. A total of 252 SNPs in FGF8, FGF10, FGFR1, FGFR2, and TBX5 passed the quality control criteria and were included in the analysis. The interactions between SNPs in different genes were assessed using Cordell's method, which fitted a conditional logistic regression model. The analysis was performed using the R‐package trio (Version 3.8.0). Bonferroni correction was used to adjust for multiple comparisons, and the overall significance threshold was set as P = 1.98 × 10−4 (0.05/252). Conditional logistic regression revealed the most significant interaction between rs2330542 in FGF10 and rs1946295 in TBX5, which remained significant (P = 9.63 × 10−6) after Bonferroni correction. The relative risk of allele C in rs2330542 (FGF10) was 1.02 (95%CI 0.81–1.28), while the relative risk was 1.42 (95%CI 1.03–1.97) when the exposure was a combination of allele C in rs2330542 and allele A in rs1946295 (TBX5). Our findings confirmed the importance of considering G × G interaction when exploring the genetic risk factors of NSCL/P. Further investigations are warranted to validate the potential interaction and reveal the biological function of FGF10/FGFR2/TBX5. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Addressing the unmet health needs of persons living with congenital anomalies in low- and middle-income countries (LMIC) is a major challenge. Registries and databases are exemplary tools capable to link research data with health programs. Since 2009, Brazil's Craniofacial Project, a multicenter and voluntary research initiative, collects socioeconomic, medical, and genetic information on individuals with craniofacial anomalies through the Brazilian Database on Craniofacial Anomalies (BDCA). This article discusses challenges to the provision of genetic assessment and counselling for individuals with syndromic oral clefts (SOC) through public health services in LMIC, such as Brazil. Subjects were selected using methods of the BDCA as described elsewhere. Among 800 records, 66 assigned as SOC with no etiologic diagnosis were preselected for genomic imbalance screening. Only 28 have timely completed basic protocol using public health services, and 22 were able to perform chromosomal microarray analysis. Pathogenic genomic imbalances were identified in 4 (18.18%) and a copy number variation of uncertain clinical significance was detected in one. Results exemplify barriers faced by the majority of the population of Brazil to reach whole genetic assessment either through public genetic services or in research settings. In this unfavorable scenario, BDCA has allowed the recognition of individuals with similar needs, optimizing the scarce genetic laboratory facilities in Brazil. Ultimately, BDCA has facilitated the translation of research into care. This experience may be successfully extended to other congenital anomalies and to LMIC with similar characteristics. A set of suggestions focusing on oral clefts is provided. [ABSTRACT FROM AUTHOR]

We compared Brazilian oral cleft (OC) frequencies between the population‐based Brazilian System of Live Birth (SINASC) and the hospital‐based Latin American Collaborative Study of Congenital Malformations (ECLAMC), trying to understand the paucity of cleft of lip and palate (CLP) in the first system. SINASC uses the International Classification of Disease version 10 (ICD‐10) for congenital defects coding, ECLAMC uses ICD‐8 with modifications. In SINASC, the CLP frequency was 1.7 per 10,000 (95% confidence limits 1.7–1.8), cleft lip (CL) 1.6 (1.5–1.7), and cleft palate (CP) 2.0 (1.9–2.1). In ECLAMC, the CLP frequency was 10.4 per 10,000 (9.0–12.1), CL 5.5 (4.5–6.7), and CP 4.4. (4.5–6.7). In SINASC, only 33% of the oral clefts were CLP, versus 51% in ECLAMC. Part of this discrepancy may have been due to the relative excess of CP and CL cases. Although congenital defect frequencies are usually lower in population than in hospital‐based registries, differences in the proportion of the main OC categories are not expected and are probably due to ICD‐10 coding issues, such as lumping of unilateral CL and CL without other specifications. ICD‐10 codes, whose deficiency for oral clefts is fully explained in the literature, lack modifiers for severity, or clinical subtypes. This paper shows the practical aspect of the ICD‐10 system deficiency in capturing cleft lip and palate (CLP) subtypes, as demonstrated in SINASC covering three million births per year. Such errors are expected to occur in any registry that uses the ICD‐10 coding system, and must be adjusted, given its relevance worldwide. [ABSTRACT FROM AUTHOR]

Background: Oral clefts are among the most common congenital anomalies. Most studies on risk factors of oral clefts have been carried out in developed countries. We investigated the associations between maternal exposures in the first trimester and oral clefts in South Vietnam. Methods: We conducted a hospital-based case-control study during October 2014- November 2015. Cases included 170 patients with nonsyndromic cleft lip with or without cleft palate and those with cleft palate only. Controls were 170 children without oral clefts, matched to each case by age and gender. Mothers were interviewed using structured questionnaire. We performed conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Passive smoking was associated with increased risk of oral clefts in univariate analysis, but not in multivariable analysis (adjusted OR [aOR]=1.68; 95% CI, 0.53-5.37). No association was observed between liver intake and oral clefts. Compared with nondrinkers, mothers who reported consumption of caffeine-containing beverages were more likely to have an infant with oral cleft (aOR=5.89; 95% CI, 1.08-32.00). Periconceptional use of folic acid and multivitamins supplementation was associated with reduced risk of oral clefts (aOR=0.01; 95% CI, 0.00-0.09 and aOR=0.03; 95% CI, 0.01-0.13, respectively). Conclusions: The results suggest no associations of maternal passive smoking or liver intake with oral clefts. Periconceptional use of folic acid or multivitamins may protect against oral clefts. Further studies are warranted to examine the roles of caffeine consumption in pregnant mothers on occurrence of oral clefts in offspring. [ABSTRACT FROM AUTHOR]

Background: As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. Methods: We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal selfreport of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. Results: Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. Conclusions: This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections. [ABSTRACT FROM AUTHOR]

The current literature shows that the cleft lip and/or palate are the most frequent congenital anomalies of all the congenital face anomalies. They can occur as part of a syndrome or they can be nonsyndromic. In the present study we compared particular growth aspects in children with cleft lip and/or palate, pathogenesis, dental anomalies accompanying various clinical forms, protocols and treatments that are most frequently used. Many patients with operated cleft lip/palate have a limited maxillary growth whereas the patients with operated cleft lip/palate have nearly normal facial growth. Most researchers believe that maxillary retrusion is secondary to the labial and/or palatal repair. As reported in other studies children with unoperated palate clefts present a small size of the anterior-posterior maxilla as well as retrusive maxilla. This type of congenital malformation is a special situation because of the treatment it requires which is an interdisciplinary approach that includes:maxillofacial surgery, plastic surgery, orthodontic treatment, ENT’s, speech therapy and paediatrics. There isn’t currently a fixed treatment scheme, schools like the German or American one use different therapeutic protocols. Also, specialized centers for treating lip and palate clefts have been established in other countries, thereby ensuring from the very beginning an adequate control and supervision of treatment that will continue all along.

Objective: To determine the association between maternal tobacco use or exposure, presence of variant transforming growth factor alpha (TGFA) gene, and the occurrence of oral clefts. Methods: The present case control study was carried out for 5 months in three tertiary government hospitals in Chennai city with a sample of 100 children (50 children with non syndromic cleft and 50 control) aged 0-24 months. The details of maternal risk factors during the period of gestation were recorded from case and control parents through a pre-validated questionnaire, following which blood samples from 92 children (46 case and 46 controls) based on consent were obtained and evaluated for TGFA gene polymorphism. Results: A significant number of case mothers (48%) were exposed to secondhand smoke during the period of gestation than their control counterparts (24%) ( P = 0.01) with an odds ratio of 2.46 (95% CI = 0.99-6.08). Electrophoresis of the restriction fragment length polymorphism (RFLP) product revealed the presence of the homozygous C1C1 allele in all the tested 92 samples with no homozygous C2C2 allele or heterozygous C1C2 allele. Conclusion: The present study has highlighted the role of passive smoking in the causation of non syndromic oral clefts in a developing country like India; however, the involvement of TGFA in causing the same disease in an ethnically Dravidian Indian population is uncertain. Clinical significance: The study has brought into forth the role of passive smoking in the development of oral clefts thereby warranting an effective public health policy to tackle the same. [ABSTRACT FROM AUTHOR]

Despite ongoing scientific debate on treatment of oro facial clefting, varying treatment schemes and surgical techniques are still being used by different cleft care teams. Early treatment -- before primary lip/nose repairs- of a neonate with a cleft lip and or palate (CLP) using a conventional maxillary plate has been appealing for cleft surgeons, dentists and also parents worldwide as this may result in reduction of cleft width and hence lessen the esthetic and functional implications involved with the overall multidisciplinary CLP treatment. In this case report we sought to introduce a rather recent approach for early management of neonates born with cleft lip palate deformity through presurgical nasoalveolar molding (PNAM) technique. Two complete cleft lip palate cases will be reported with illustrations of laboratory and clinical steps involved. [ABSTRACT FROM AUTHOR]

Background Nonsyndromic oral clefts are craniofacial malformations, which include cleft lip with or without cleft palate. The etiology for oral clefts is complex with both genetic and environmental factors contributing to risk. Previous genome-wide association ( GWAS) studies have identified multiple loci with small effects; however, many causal variants remain elusive. Methods In this study, we address this by specifically looking for rare, potentially damaging variants in family-based data. We analyzed both whole exome sequence ( WES) data and whole genome sequence ( WGS) data in multiplex cleft families to identify variants shared by affected individuals. Results Here we present the results from these analyses. Our most interesting finding was from a single Syrian family, which showed enrichment of nonsynonymous and potentially damaging rare variants in two genes: CASP9 and FAT4. Conclusion Neither of these candidate genes has previously been associated with oral clefts and, if confirmed as contributing to disease risk, may indicate novel biological pathways in the genetic etiology for oral clefts. [ABSTRACT FROM AUTHOR]

Objective: Early life exposure to anesthesia and surgery is suspected to associate with cognitive impairment later in life. We compared academic achievement among adolescents with cleft lip only (CL), cleft palate only (CP), and cleft lip and cleft palate (CLP) with a noncleft control group to investigate whether outcome depends on timing and number of operations during childhood and/or type of oral cleft. Design: Nationwide register-based follow-up study. Setting: Danish birth cohort 1986 to 1990. Participants: Five hundred fifty-eight children with isolated CL (n = 171), CLP (n = 222), or CP (n = 195), of which 509 children had been exposed to anesthesia and one or more cleft operation(s), and a 5% sample of the birth cohort (n = 14,677). Main Outcome Measure(s): Test score in the Danish standardized ninth-grade exam and proportion of nonattainment, defined as "results for ninth-grade exam unavailable." Data adjusted for sex, birth weight, parental age, and parental level of education. Results: Compared to controls, children with CL achieved higher scores (mean difference 0.12, 95% Cl -0.05; 0.29) and children with CLP presented with lower scores (mean difference -0.06, 95% Cl -0.21; 0.09), albeit both statistically insignificant. Children with CP achieved significantly lower scores, mean difference -0.20 (95% Cl -0.38; -0.03). Odds ratios for nonattainment at final exam were: CL 0.79 (95% Cl 0.46; 1.35), CLP 1.07 (95% Cl 0.71; 1 61) CP 2.59 (95% Cl 1.78; 3.76). Conclusions: Oral cleft type rather than number and timing of anesthesia and operations associate to poorer academic performance. Although a potential neurotoxic effect due to anesthetic agents is not reflected in the data, it cannot be completely excluded. [ABSTRACT FROM AUTHOR]

Introduction: The interaction between several cell populations or many genes and the coordination of multiple signal transmission pathways can lead to defects such as orofacial clefts (OFCs). Herein, a systematic review was designed to evaluate a group of important biomarkers (matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs]) in human cases with OFCs., Material and Methods: Four databases including PubMed, Scopus, Web of Science, and Cochrane Library databases were searched until March 10, 2023, without any restriction. STRING, the protein-protein interaction (PPI) network software, was applied to investigate the functional interactions among the examined genes. The effect sizes including odds ratio (OR) dealing with a 95% confidence interval (CI), were extracted by the Comprehensive Meta-Analysis version 2.0 (CMA 2.0) software., Results: Thirty-one articles were entered into the systematic review that four articles were analyzed in the meta-analysis. Single studies reported that several polymorphisms of MMPs (rs243865, rs9923304, rs17576, rs6094237, rs7119194, and rs7188573); and TIMPs (rs8179096, rs7502916, rs4789936, rs6501266, rs7211674, rs7212662, and rs242082) had an association with OFC risk. There was no significant difference for MMP-3 rs3025058 polymorphism in allelic (OR: 0.832; P=0.490), dominant (OR: 1.177; P=0.873), and recessive (OR: 0.363; P=0.433) models and MMP-9 rs17576 polymorphism in an allelic model (OR: 0.885; P=0.107) between the OFC cases and the controls. Based on immunohistochemistry reports, three MMPs (MMP-2, MMP-8, and MMP-9) and TIMP-2 had significant correlations with several other biomarkers in OFC cases., Conclusions: MMPs and TIMPs can impact the tissue and cells affected by OFCs and the process of apoptosis. The interaction between some biomarkers with MMPs and TIMPs (e.g., TGFb1) in OFCs can be interesting for future research., (Copyright © 2023 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Nonsyndromic oral clefts (NSOC) are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1 CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp), 0.169 (173 bp), 0.096 (171 bp) and 0.67 (169 bp). A transmission disequilibrium test with a family-based association test (FBAT) software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005). These results suggest that the CA repeat polymorphism of the MSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.

In this report, we have reanalyzed genotyping data in a collection of families from South America based on maternal origin. Genotyping analysis was performed at the Craniofacial Anomalies Research Center at the University of Iowa. These genotypes were derived from genomic DNA samples obtained from blood spots from children born with isolated orofacial clefts in 45 hospitals located in eight countries (Argentina, Bolivia, Brazil, Chile, Ecuador, Paraguay, Uruguay, and Venezuela) collaborating with ECLAMC (Latin American Collaborative Studies of Congenital Malformations) between January 1998 and December 1999. Dried blood samples were sent by regular mail to the Laboratory of Congenital Malformations, Federal University of Rio de Janeiro. Previous findings suggested that mitochondrial haplotype D is more commonly found among cleft cases born in South America. We hypothesized that association of certain genes may depend upon the ethnic origin, as defined by population-specific markers. Therefore, we tested if markers in MTHFR (5,10-methylenetetrahydrofolate reductase) and RFC1 (reduced folate carrier 1) were associated with oral clefts, depending on the maternal origin defined by the mitochondrial haplotype. Transmission distortion of alleles in MTHFR C677T and RFC1 G80A polymorphic variants was tested in 200 mother/affected child pairs taking into consideration maternal origin. RFC1 variation was over-transmitted to children born with cleft lip only (P = 0.017) carrying mitochondrial DNA haplotypes other than haplotype D. Our results provide a new indication that variation in RFC1 may contribute to cleft lip only. Future studies should investigate the association between oral clefts and RFC1 based on more discrete phenotypes.

Chromosome microarray analysis (CMA) has proven to be a powerful tool in postnatal patients with intellectual disabilities. However, the diagnostic capability of CMA in patients with congenital oral clefts remain mysterious. Here, we present our clinical experience in implementing whole-genome high-resolution SNP arrays to investigate 33 patients with syndromic and nonsyndromic oral clefts in whom standard karyotyping analyses showed normal karyotypes. We aim to identify the genomic aetiology and candidate genes in patients with congenital oral clefts. CMA revealed copy number variants (CNVs) in every patient, which ranged from 2 to 9 per sample. The size of detected CNVs varied from 100 to 3.2 Mb. In 33 patients, we identified six clinically significant CNVs. The incidence of clinically significant CNVs was 18.2% (6/33). Three of these six CNVs were detected in patients with nonsyndromic clefts, including one who presented with isolated cleft lip with cleft palate (CLP) and two with cleft palate only (CPO). The remaining three CNVs were detected in patients with syndromic clefts. However, no CNV was detected in patients with cleft lip only (CLO). The six clinically significant CNVs were as follows: 8p23.1 microduplication (198 kb); 10q22.2-q22.3 microdeletion (1766 kb); 18q12.3 microduplication (638 kb); 20p12.1 microdeletion (184 kb); 6q26 microdeletion (389 kb); and 22q11.21-q11.23 microdeletion (3163 kb). In addition, two novel candidate genes for oral clefts, KAT6B and MACROD2, were putatively identified. We also found a CNV of unknown clinical significance with a detection rate of 3.0% (1/33). Our results further support the notion that CNVs significantly contributed to the genetic aetiology of oral clefts and emphasize the efficacy of whole-genome high-resolution SNP arrays to detect novel candidate genes in patients with syndromic and nonsyndromic clefts. [ABSTRACT FROM AUTHOR]

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27,95% confidence interval (CI): 1.11,1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR =1.14, 95% CI: 1.02,1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic. [ABSTRACT FROM AUTHOR]

Introduction: Oral cleft is a common craniofacial birth defect that leads to long-lasting adverse outcomes. In Thailand, there have been two studies of the prevalence of oral clefts using data from university hospitals during 1969 through 1978 and 1988 through 1999, which found prevalence rates of 1.23 and 1.22 per 1000 live births, respectively. Objective: The primary outcome was to assess the prevalence of oral clefts from the birth defects registry during 2009 through 2013 in three provinces in southern Thailand. The secondary outcomes were to correlate the risk of oral cleft and maternal age. Design: Population-based study. Setting: Four hundred sixty-seven hospitals in three provinces in southern Thailand. Participants: Oral cleft cases and maternal data--including live births, stillbirths, and termination of pregnancy following a prenatal diagnosis--were collected from the birth defects registry. Results: Of the total 186,393 births, there were 269 oral cleft cases, giving an average prevalence of 1.44 per 1000 births (95% CI, 1.22-1.63). The most common cleft type was cleft lip and palate (45.0%), followed by cleft palate (29.0%), with 15.6% syndromic cleft. The mean maternal age was 28.0 ± 6.4 years. There were no differences in prevalence of oral clefts among the different maternal age groups. However, advanced maternal age 35+ years was associated with syndromic cleft children. Conclusions: The prevalence of oral clefts was 1.44 per 1000 live births, with 15% of cases having an associated congenital anomaly or a recognized syndrome. Increased maternal age was associated with a higher prevalence of syndromic cleft. [ABSTRACT FROM AUTHOR]

Many folate-related genes have been investigated for possible causal roles in neural tube defects (NTDs) and oral clefts. However, no previous reports have examined the major gene responsible for folate uptake, the proton-coupled folate transporter ( SLC46A1). We tested for association between these birth defects and single nucleotide polymorphisms in the SLC46A1 gene. The NTD study population included 549 complete and incomplete case-family triads, and 999 controls from Ireland. The oral clefts study population comprised a sample from Utah (495 complete and incomplete case-family triads and 551 controls) and 221 Filipino multiplex cleft families. There was suggestive evidence of increased NTD case risk with the rs17719944 minor allele (odds ratio (OR): 1.29; 95% confidence intervals (CI): [1.00-1.67]), and decreased maternal risk of an NTD pregnancy with the rs4795436 minor allele (OR: 0.62; [0.39-0.99]). In the Utah sample, the rs739439 minor allele was associated with decreased case risk for cleft lip with cleft palate (genotype relative risk (GRR): 0.56 [0.32-0.98]). Additionally, the rs2239907 minor allele was associated with decreased case risk for cleft lip with cleft palate in several models, and with cleft palate only in a recessive model (OR: 0.41; [0.20-0.85]). These associations did not remain statistically significant after correcting for multiple hypothesis testing. Nominal associations between SLC46A1 polymorphisms and both Irish NTDs and oral clefts in the Utah population suggest some role in the etiology of these birth defects, but further investigation in other populations is needed. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cleft lip and/or palate (CL/P) is a major congenital defect with complex etiology, including multiple genetic and environmental factors. Approximately two thirds of the cases are not accompanied by other anomalies and are called nonsyndromic (NS). In the present study, we performed transmission distortion analysis of the MSX1-CA, TGFB3-CA and MTHFR-C677T polymorphisms in 60 parent-child triads, in which the NS-CL/P affected child had at least one affected parent. No association with genes MSX1 or TGFB3 was found, but the results were suggestive of an association of the MTHFR-C677T polymorphism with NS-CL/P.

Background: The prevalence of congenital heart defects (CHD) in children with cleft lips (CLs) and palate (CP) is reportedly higher than the general population. Several studies have described diverse rate of CHD in different localities. Aims and Objectives: To the authors′ knowledge, the frequency and pattern of CHD among children with CLs and CP has not described in this geopolitical zone. Materials and Methods: This is a retrospective study of the echocardiographic records of all cases of CL and CP seen over a 4 years period, between November, 2010 and October, 2013. Data were analyzed and expressed using frequency tables and percentages. Results: A total 30 children were referred for echocardiographic screening (ECGS) during the period. There were 17 males and 13 females, giving a male:female of about 1:1. The age range was between 15 days and 12 years with a median age of 4 months. There were 6 (20%) cases of CHDs. Conclusions: The relatively high rate of CHD among children with oral clefts in this study justifies the need for ECGS for these categories of children.

The article discusses assessment of whether congenitally missing teeth occur more commonly in women diagnosed with cancer in the reproductive system than in healthy women. It mentions additional evidence that the genes involved in colorectal cancer may also be involved in tooth development; and also mentions reliability of self-report of dental agenesis.

Background: Parents of children with oral clefts may be impacted psychosocially in several ways, but empirical evidence remains relatively sparse. The aim of this study was to identify predictors of psychosocial well-being of parents of affected children. Methods: The study included a total sample of 287 parents (171 mothers and 116 fathers) of children with oral clefts. Parents completed validated psychosocial instruments to measure social avoidance and distress, fear of negative evaluation scale, self-esteem and interpersonal support. Regression analysis was used to evaluate how selected child, parent and household characteristics relate to psychosocial outcomes focusing on child's cleft type, sex and age, differences between mothers and fathers, marital status and household income. Results: Fathers had higher self-esteem than mothers (P = 0.01) and lower concern of being negatively judged by others (P<0.0001) but also had lower perception of having someone to talk to about their problems (P = 0.01). High household income was associated with greater self-esteem and perception of social support (<0.05). Parents of male affected children had greater perception of social support than parents of female affected children (P = 0.04). No significant differences in parental psychosocial status measures were found by cleft type. Similarly, there is little evidence of changes with child age, except for an increase in parental distress and decline in self-esteem during mid-adolescence (age 15-17 years). Conclusions: The results indicate that mothers and fathers of children with oral clefts may differ in their psychosocial adjustment and that mothers may overall experience more psychosocial problems than fathers. Also, parents from less wealthy households may be at greater risk. Parental psychosocial status should be considered in holistic family-based treatment approaches to reduce burden on affected families and improve their well-being. [ABSTRACT FROM AUTHOR]

Results from previous studies on maternal folic acid intake and infant oral clefts are inconclusive. The aim of the present study was to investigate the association between women’s use of folic acid and/or multivitamin supplements and the risk for oral cleft in the newborn. We used data from the Medical Birth Registry of Norway based on all births in Norway from 1999 to 2013. A total of 528 220 women had 880 568 pregnancies, resulting in 896 674 live births and stillbirths, of which 1623 had oral clefts (isolated oral clefts, n 1311; non-isolated oral clefts, n 312). Altogether, 21·5 % of women were vitamin supplement users before pregnancy. The birth prevalence of oral clefts was 1·81/1000 live births and stillbirths. Relative risks (RR) were estimated with log-binomial regression. For pregnancies with maternal use of vitamins, the adjusted RR for clefts overall was 0·90 (95 % CI 0·79, 1·04). The adjusted RR for cleft palate only (n 586) was 0·84 (95 % CI 0·66, 1·06) and that for cleft lip with or without cleft palate (n 1037) was 0·94 (95 % CI 0·79, 1·13). Associations were stronger for cleft cases that occurred in combination with other malformations (adjusted RR 0·63; 95 % CI 0·45, 0·88), although vitamin supplements provided no protection against isolated clefts (adjusted RR 0·98; 95 % CI 0·84, 1·15). In conclusion, our study demonstrates no statistically significant association between vitamin use and isolated oral clefts. However, we found lower risk for oral clefts that occurred in combination with other malformations. [ABSTRACT FROM AUTHOR]

ABSTRACT Nonsyndromic orofacial cleft (NSOFC) is a complex disease of still unclear genetic etiology. To investigate the contribution of rare epithelial cadherin ( CDH1) gene variants to NSOFC, we target sequenced 221 probands. Candidate variants were evaluated via in vitro, in silico, or segregation analyses. Three probably pathogenic variants (c.760G>A [p.Asp254Asn], c.1023T>G [p.Tyr341*], and c.2351G>A [p.Arg784His]) segregated according to autosomal dominant inheritance in four nonsyndromic cleft lip with or without cleft palate (NSCL/P) families (Lod score: 5.8 at θ = 0; 47% penetrance). A fourth possibly pathogenic variant (c.387+5G>A) was also found, but further functional analyses are needed (overall prevalence of CDH1 candidate variants: 2%; 15.4% among familial cases). CDH1 mutational burden was higher among probands from familial cases when compared to that of controls ( P = 0.002). We concluded that CDH1 contributes to NSCL/P with mainly rare, moderately penetrant variants, and CDH1 haploinsufficiency is the likely etiological mechanism. [ABSTRACT FROM AUTHOR]

Oral clefts are among the most common birth defects affecting thousands of newborns each year, but little is known about their potential long-term consequences. In this paper, we explore the impact of oral clefts on health care utilization over most of the lifespan. To account for time-invariant unobservable parental characteristics, we compare affected individuals with their own unaffected siblings. The analysis is based on unique data comprising the entire cohort of individuals born with oral clefts in Denmark tracked until adulthood in administrative register data. We find that children with oral clefts use more health services than their unaffected siblings. Additional results show that the effects are driven primarily by congenital malformation-related hospitalizations and intake of anti-infectives. Although the absolute differences in most health care utilization diminish over time, affected individuals have slightly higher utilization of some health care services in adulthood (particularly for diseases of the nervous and respiratory system). These results have important implications for affected individuals, their families, and their health professionals. [ABSTRACT FROM AUTHOR]