Search

The aim of this study was to review the effects of early and late hard palate repair on maxillary growth. PubMed, Scopus, Web of Science, LILACS, Cochrane Library CENTRAL databases, OpenGrey, Google Scholar, and Clinical Trials were searched using a PICO strategy, with terms related to unilateral cleft lip and palate (UCLP) and timing of repair. Methodological quality evaluation was carried out using the Fowkes and Fulton guidelines, and quality (or certainty) of evidence and strength of recommendations were evaluated using GRADE (grading of recommendations, assessment, development and evaluation). Five retrospective and non-randomized studies were included in the study. Folkes and Fulton assessment showed a high risk of bias in all articles and very low levels of certainty (GRADE). The results showed conflicting findings for comparisons of the effects of timing of repair of hard palate in UCLP. Two studies presented better maxillary growth in a group operated on later (18 months after birth), two presented no differences between the results, and another presented better results in the group operated on earlier than 18 months of age. At this point, it cannot be proven or refuted that postponing hard palate surgery brings benefits for maxillary growth. Studies included in this review did not show similar conclusions. Randomized clinical trials present some ethical issues that make them difficult to perform. [ABSTRACT FROM AUTHOR]

Orofacial clefts (OFCs) are among the most common congenital craniofacial malformations, including cleft lip with or without cleft palate as the core symptoms. Developmental or functional defects in neural crest cells (NCCs) that contribute to craniofacial morphogenesis are involved in OFC development. Previous studies have suggested that oxidative stress in NCCs is involved in the development of OFCs, suggesting that the anti-oxidative activity of folic acid (FA) could have protective effects. However, studies of human-derived NCCs are limited, as these cells are predominantly active during the embryonic stage. In this study, the effects of oxidative stress and FA were evaluated in human OFCs. In particular, NCC-derived stem cells from human exfoliated deciduous teeth (SHEDs) were obtained from 3 children with non-syndromic cleft lip with cleft palate (CLPs) and from 3 healthy children (CTRLs). Mitochondrial reactive oxygen species (ROS) levels were significantly higher in CLPs than in CTRLs and were associated with lower mRNA expression levels of superoxide dismutase 1 (SOD1) and decreased cell mobility. In addition, significantly greater vulnerability to pyocyanin-induced ROS, mimicking exogenous ROS, was observed in CLPs than in CTRLs. These vulnerabilities to endogenous and exogenous ROS in CLPs were significantly improved by FA. These results indicated that the transcriptional dysregulation of SOD1 in NCCs is an oxidative stress-related pathological factor in OFCs, providing novel evidence for the benefits of perinatal anti-oxidant supplementation, including FA, for the management of these common deformities. • OFC patient-derived SHEDs were used as a model of human neural crest cells. • Endogenous mitochondrial ROS levels were high in OFC patient-derived SHEDs. • SOD1 levels and cell motility were decreased in OFC patient-derived SHEDs. • Pyocyanin-induced exogenous ROS damaged OFC patient-derived SHEDs. • Folic acid improved the vulnerability to ROS in OFC patient-derived SHEDs. [ABSTRACT FROM AUTHOR]

Objectives: Congenital anomalies are the biggest cause of prenatal, perinatal, or infant mortality and morbidity. A total of 15% of congenital abnormalities involve the craniofacial and oral segment. Orofacial cleft (OC) is one of the most common examples of congenital abnormalities. One example of OC is cleft lip and/or palate (CL/P). The occurrence of the incident varies depending on geographical location, ethnicity, race, environmental exposure, and socioeconomic status of the patients. The aim of the study was to investigate the variation of non-syndromic CL/P (nsCL/P) in Yayasan Surabaya CLP Center, East Java, Indonesia, as well as the number of occurrences of clefts in each gender. Materials and Methods: An analytical observational study with cross-sectional and blind total sampling method was presented. Data obtained from Yayasan Surabaya CLP Center were grouped by type and classified by the LAHSHAL classification system. The numbers were calculated and then divided into occurrence per gender and per family history. A descriptive analysis was applied and then presented in table form. Results: The number of patients with cleft lip and palate (CLP), cleft lip (CL), and cleft palate (CP) were 163, 57, and 16, respectively. The more detailed type: ...SHAL, .....AL, and ..HSH.., had the highest number of cases, which were 79, 28, and 10, respectively. Conclusion: Most types of CL/P at Yayasan Surabaya CLP Center were CLP, followed by CL and finally CP. The incidence of CLP and CL was more common in men, whereas CP was more common in women. [ABSTRACT FROM AUTHOR]

Background. Stereophotogrammetry can be used to study facial morphology in both healthy individuals as well as subjects with orofacial clefts because it shows good reliability, ability to capture images rapidly, archival capabilities, and high resolution, and does not require ionizing radiation. This study aimed to compare the three-dimensional (3D) facial morphology of infants born with unilateral cleft lip and palate (UCLP) with an age-matched normative 3D average face before and after primary closure of the lip and soft palate. Methods. Thirty infants with a non-syndromic complete unilateral cleft lip, alveolus, and palate participated in the study. Three-dimensional images were acquired at 3, 6, 9, and 12 months of age. All subjects were treated according to the primary surgical protocol consisting of surgical closure of the lip and the soft palate at 6 months of age. Three-dimensional images of UCLP patients at 3, 6 (pre-treatment), 9, and 12 months of age were superimposed on normative datasets of average facial morphology using the children’s reference frame. Distance maps of the complete 3D facial surface and the nose, upper lip, chin, forehead, and cheek regions were developed. Results. Assessments of the facial morphology of UCLP and control subjects by using color-distance maps showed large differences in the upper lip region at the location of the cleft defect and an asymmetry at the nostrils at 3 and 6 months of age. At 9 months of age, the labial symmetry was completely restored although the tip of the nose towards the unaffected side showed some remnant asymmetry. At 12 months of age, the symmetry of the nose improved, with only some remnant asymmetry noted on both sides of the nasal tip. At all ages, the mandibular and chin regions of the UCLP patients were 2.5–5 mm posterior to those in the average controls. Conclusion. In patients with UCLP deviations from the normative average 3D facial morphology of age-matched control subjects existed for the upper lip, nose, and even the forehead before lip and soft palate closure was performed. Compared to the controls symmetry in the upper lip was restored, and the shape of the upper lip showed less variation after primary lip and soft palate closure. At this early age, retrusion of the soft-tissue mandible and chin, however, seems to be developing already. [ABSTRACT FROM AUTHOR]

Cleft lip and palate (CLP) are commonly occurring birth defects which occur due to failure of fusion of various developmental processes of the face, leading to a visible defect in the lip and palate. In severe cases, this defect may extend over the face, thus causing facial clefts. The present case of a 7-year-old girl is unique in the sense that she has right and left side facial clefts of different severity with bilateral accessory maxilla, extra set of dentition, unilateral CLP of the right side, and a double soft palate. Other less associated findings in the case are severe maxillary protrusion, complex open bite, downward and backward rotation of mandible, and incompetent lips with apparently no limb deformities. With some relevant data in hand, we present this case for various suggestions and best possible treatment plan. [ABSTRACT FROM AUTHOR]

Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominantly inherited cancer syndrome associated with a high risk for diffuse gastric and lobular breast cancer, caused by heterozygous CDH1 germline mutations. Of note, also cleft lip/palate (CLP) has been described in few HDGC families. Here we report on an extensive pedigree presenting with HDGC, CLP and a CDH1 splice site mutation (c.687 + 1G > A) and review the literature for families with CDH1 mutations, HDGC and CLP. Transcript analysis showed that the c.687 + 1G > A mutation leads to loss of the last 42 bp of exon 5 and is consequently predicted to cause loss of 14 amino acids in the first extracellular cadherin repeat (EC) domain. Five mutation carriers developed diffuse gastric cancer and four individuals presented with CLP. Wild type CDH1 expression levels did not differ between CDH1 mutation carriers with CLP compared to those without CLP. Beside this extensive pedigree, we outline another previously unreported HDGC/CLP family with a CDH1 (c.1711 + 1G > C) germline mutation in this study. Review of the literature revealed a significant enrichment of CDH1 mutations within the EC domains in CLP/HDGC families (Fisher's exact test, p = 0.007) in comparison to CDH1 mutations associated with HDGC only. Report of further CLP/HDGC associated mutations is necessary to confirm this observation. This study highlights that CLP represents an important phenotypic feature of CDH1 germline mutation carriers and emphasizes the inclusion of CLP in the HDGC testing criteria. The underlying causes for the appearance of variable phenotypes in CDH1 mutation carriers could include genetic variation, epigenetic changes and environmental factors and should be investigated in future studies. [ABSTRACT FROM AUTHOR]

Objectives: To assess the influence of involuntary facial expressions on 3D facial stereophotogrammetry reproducibility in children with and without unilateral cleft lip, alveolus and palate (UCLP) aged 3–18 months. Materials and methods: Three to eight 3D facial images per time point were acquired within 10 min of 31 children with UCLP and 50 controls at 3, 12 and 18 months of age. 3D mapping of two 3D facial images per subject per age was performed. Distance kits of the full face and nasolabial area were calculated. Results: In the total subject pool, mean variation between two 3D facial images ranged from 0.38–0.88 mm. There were no significant differences within groups for the various ages. Variation between controls and UCLP subjects did not differ significantly. Variation was higher in the nasolabial area than in the full face. Conclusions: The influence of involuntary facial expressions on the estimation of facial growth should not be underestimated, especially in the nasolabial region of UCLP subjects aged 3 months. To improve 3D facial imaging reliability, image capturing should be performed by a trained photographer following a meticulous image capturing protocol, including thorough review after capture. Clinical relevance: Facial 3D stereophotogrammetry is a useful tool for monitoring facial growth longitudinally in young children with facial deformities, as no radiation is involved and image capture is easy and fast. It can be performed reliably in children with and without UCLP aged 3–18 months by an experienced photographer utilising a meticulous image capturing protocol. [ABSTRACT FROM AUTHOR]

Objective: Distal-less 4 (DLX4) was recently identified as the causative gene for a syndromic form of cleft lip with or without cleft palate, and further biological analyses have established the importance of Dlx4 gene in craniofacial development, which suggested DLX4 as a promising candidate to further investigate any possible association between DLX4 polymorphisms and risk to nonsyndromic orofacial clefts (NSOFCs). Design: Single-nucleotide polymorphisms (SNPs) with minor allele frequency >5% in the Han Chinese population which locate in the 5' flanking region, 5'/3'-untranslated region, or coding region with nonsynonymous changes in DLX4 were selected. Four SNPs (rs58769681, rs1058562, rs1058564, and rs8066341) were thus included in the following genotyping using the TaqMan 5'-exonuclease allelic discrimination assay in a case-control cohort with 1522 individuals. Results: None of SNPs were associated with NSOFCat the allele and genotype levels in general and stratified single-marker analysis, including genotypic distributions under different modes of inheritance. In linkage disequilibrium (LD) analysis, we found strong LD (r² > 0.8) between any 2 of the SNPs, respectively. Further haplotyping identified haplotypes C-C (formed by rs1058564 and rs1058562) and C-C-A (formed by rs1058564, rs1058562, and rs58769681) which reached the significance threshold (P < .05); nevertheless, none of them survived the multiple comparison correction. Conclusions: Our findings indicated the hypothesis that DLX4 variants contributing to NSOFC risk should be interpreted with caution. Further replications in diverse ethnic origins and larger cohorts are still warranted. [ABSTRACT FROM AUTHOR]

Genome‐wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low‐frequency variants may account for some of the "missing" heritability. Therefore, we scanned low‐frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP‐Seq studies in craniofacial tissues or cell lines contained multiple low‐frequency (0.01–1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low‐frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p‐value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p‐value = .001). These findings suggest that low‐frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs. [ABSTRACT FROM AUTHOR]

The Rationale: Craniofacial clefts are rare malformations. According to their localization, 15 types are classified. Patient Concerns: They referred to impaired eyelid function, lateral protection of the eye-bulb, and aesthetic appearance. Diagnosis: A three-dimensional-computerized tomography scan and a stereolithographic model led to the diagnosis of a rare intraorbital Tessier 6 cleft. Treatment: A newly designed lateral orbital rim osteotomy, presurgically simulated on a stereolithographic model, was performed to forward position the lateral orbital rims bilaterally by osteodistraction. Outcomes: Both lateral orbital rims were distracted anteriorly for around 12 mm over a period of 9 weeks, without any side effects to the patient. Take-away Lessons: In this intraorbital Tessier 6 cleft, an improved eyelid function with better lateral protection of the eye bulb and more favorable aesthetic appearance was achieved with this novel lateral orbital rim osteotomy. [ABSTRACT FROM AUTHOR]

Orofacial cleft comprise a range of congenital deformities and are most common head and neck congenital malformations. Cleft of the lip are more common in males. Cleft lip can vary from a small notch in the vermilion border to a complete separation involving skin, muscles, mucosa, tooth and bone. Clefts may be unilateral or bilateral and can involve the alveolar ridge. The incidence of the cleft palate is more prevalent in females. Patient with unilateral CLP were frequently more affected by dental anomalies than bilateral CLP. The incidence of congenitally missing teeth, especially lateral incisors adjacent to the alveolar cleft is high.2,4 If not missing, these teeth may be malformed and malposed. There are various treatment modalities of definitive prosthesis for unilateral and bilateral CLP patients after completion of orthodontic treatment such as; conventional multi-unit fixed partial denture (FPD), fiber-reinforced composite resin-bonded FPD, conventional removable partial denture (RPD) and combination of fixed and removable partial dentures. This article represents rehabilitation of patient with cleft lip and palate in the anterior aesthetic zone. [ABSTRACT FROM AUTHOR]

Background: It is widely accepted that cleft lip with or without cleft palate (CL/P) results from the complex interplay between multiple genetic and environmental factors. However, a robust investigation of these gene-environment (GxE) interactions at a genome-wide level is still lacking for isolated CL/P.Materials and Methods: We used our R-package Haplin to perform a genome-wide search for GxE effects in isolated CL/P. From a previously published GWAS, genotypes and information on maternal periconceptional cigarette smoking, alcohol intake, and vitamin use were available on 1908 isolated CL/P triads of predominantly European or Asian ancestry. A GxE effect is present if the relative risk estimates for gene-effects in the offspring are different across exposure strata. We tested this using the relative risk ratio (RRR). Besides analyzing all ethnicities combined (“pooled analysis”), separate analyses were conducted on Europeans and Asians to investigate ethnicity-specific effects. To control for multiple testing, q-values were calculated from the p-values.Results: We identified significant GxVitamin interactions with three SNPs in “Estrogen-related receptor gamma” (ESRRG) in the pooled analysis. The RRRs (95% confidence intervals) were 0.56 (0.45–0.69) with rs1339221 (q = 0.011), 0.57 (0.46–0.70) with rs11117745 (q = 0.011), and 0.62 (0.50–0.76) with rs2099557 (q = 0.037). The associations were stronger when these SNPs were analyzed as haplotypes composed of two-SNP and three-SNP combinations. The strongest effect was with the “t-t-t” haplotype of the rs1339221-rs11117745-rs2099557 combination [RRR = 0.50 (0.40–0.64)], suggesting that the effects observed with the other SNP combinations, including those in the single-SNP analyses, were mainly driven by this haplotype. Although there were potential GxVitamin effects with rs17734557 and rs1316471 and GxAlcohol effects with rs9653456 and rs921876 in the European sample, respectively, none of the SNPs was located in or near genes with strong links to orofacial clefts. GxAlcohol and GxSmoke effects were not assessed in the Asian sample because of a lack of observations for these exposures.Discussion/Conclusion: We identified significant interactions between vitamin use and variants in ESRRG in the pooled analysis. These GxE effects are novel and warrant further investigations to elucidate their roles in orofacial clefting. If validated, they could provide prospects for exploring the impact of estrogens and vitamins on clefting, with potential translational applications.

Background and aims. The aim of the present study is to determine the incidence of MTHFR C677 T and A1298C muta-tions in Iranian patients with cleft lip and/or cleft palate. Materials and methods. We screened 61 Iranian patients with cleft lip and/or cleft palate for mutations in the two alleles of MTHFR gene associated with cleft lip and/or palate: A1298C and C677T, using Polymerase Chain Reaction following by RFLP. Results. The 677T and 1298C homozygote genotypes showed a frequency of 36.1% and 11.4%, respectively. Combined genotype frequencies in newborns having oral clefts showed that the highest genotype was 677TT/1298AA (22.9%) and 677TT/1298CC genotypes were not observed. Conclusion. The results showed that 65.6% of all patients had at least one T mutant allele in C677T and 58.9% C mutant allele for A1298C. According to the frequencies of homozygosity of mutant alleles, it could be said that MTHFRgenotype of 677TT shows a greater role in having oral clefts.

Background. Several studies observed metabolic disorders in pregnancy as risk factors for birth defects, including orofacial clefts. Diabetes is associated with approx. 10% of the pregnancies, but in Romania, less than 5%. An obese and diabetic woman has 3 times more risk for an offspring with a craniofacial defect than healthy women suggesting that diabetes mellitus contributes to their pathogenesis with complex mechanisms. Case report. We present the case of a newborn 4 days old, male with neonatal hypoglycemia, cleft lip and proportionate (symmetric) macrosomia. His mother is a 35 years old Caucasian woman with no important personal risk factors and no known history of diabetes mellitus. The glucose tolerance test performed to the mother at about 10 weeks during pregnancy led to the diagnosis of gestational diabetes. Discussion. The gestational diabetes mellitus diagnosed since the 10th week of pregnancy, the hyperglycemia status during pregnancy and the fetal overgrowth (macrosomia at birth) indicate the possible factors that lead to the Orofacial cleft (OFC). Conclusion. With the increased prevalence of obesity, diabetes, and the evidence of association of these syndromes with OFCs, it is recommended that mothers planning to become pregnant to follow healthy habits, maintain healthy weight, and be screened for possible diabetes prior to conception and early in pregnancy. [ABSTRACT FROM AUTHOR]

Background The best outcome of orofacial cleft (OFC) management is predicated on appropriate surgical intervention and patients' regular attendance of scheduled review appointments. Non-attendance at scheduled attendance by patients can adversely affect the eventual outcome of management. The study aimed to determine the factors responsible for missed scheduled review appointment following cleft repair surgery. Methods This is a prospective cohort study of consenting parents of all children that had cleft repair surgery between February 2012 and March 2013. A semi-structured questionnaire with information including socio-demographic characteristics and reason for failure to attend five scheduled review appointments was used. Results Sixty-two parents with completed information were included in the analysis. There was a progressive drop in the number of patients attending review appointments over time and this was statistically significant (p=0.0001). The reasons for missed appointment varied, including medical illness of patient or parent and financial constraints. The statistical significant predictors of attendance at the early review follow-up clinic were living within Abeokuta (OR 4.431, 95%CI 1.224-16.041, p=0.023) and earning higher income (OR 5.118, 95%CI 1.423-18.410, p=0.012). Conclusions Missed appointment was common over time. Illness, pressure of work and financial constraints were mainly responsible for non-attendance. There is need for cleft care plan that takes care of both caregiver and patient and also for it to be more accessible. [ABSTRACT FROM AUTHOR]

Abstract There is a growing demand for surgical care in South America, particularly for patients with congenital orofacial clefts (OFCs). Short-term surgical missions (STSMs) have emerged as a means to deliver surgical expertise and alleviate this demand. The aim of this study was to review the quantity and quality of peer-reviewed reports on OFC repairs performed by STSMs in South America. A literature search was conducted using the PubMed, Embase, Web of Science, and SciELO databases. The search was limited to articles published in English and Spanish. Descriptive statistics were used for the data analysis. The search yielded 65 studies related to OFCs. Eight (12.3%) were selected for full-text review. Only five (7.7%) articles met the inclusion criteria. The diverse study designs and heterogeneous types of data assessment among the selected studies hindered a comparison between them. This review found a sparse number of publications pertaining to OFC missions to South America. The articles that were included demonstrated inconsistencies in reporting patient care data. There is a need for a more efficient, streamlined method of reporting humanitarian missions for OFC repairs in order for healthcare professionals to fulfill research and ethical obligations and offer the best practices in patient-centered care. [ABSTRACT FROM AUTHOR]

Background: Every infant should receive a comprehensive health-care risk assessment irrespective of their circumstances. Numerous reports have shown association between orofacial cleft and weight loss, feeding disability. The purpose of this study was to understand the anxiety and depression among mothers and knowledge, attitude, and practice skills of feeding plate obturators among dental practitioners. Aim: The aim of the study is to evaluate the knowledge, attitude, and practice of feeding plate obturators among dental practitioners. Materials and Methods: The study involved a survey of 100 private dental practitioners all among India. The pre-tested questionnaire on the awareness and fabrication of feeding plate obturators among the dental practitioners was used to collect the data related. The data collected were subjected to statistical analysis using frequency of responses and standard deviation. Results: The data acquired from this survey exhibited that 85% of dentists receive a frequency of cases with orofacial clefts of around 10/6 months, though these patients require a multidisciplinary approach through various phases of their growth, parents bother about their feeding disabilities, as 70% of patients age approaching clinic was around 15-45 days. Hence, the primary treatment approach could be a feeding plate obturator which helps them in feeding and swallowing. Whereas 55% of clinicians fabricate feeding plate obturators on their own and 30% depends on other clinicians for such cases. Usually, the obturators were been delivered in 1 or 2 days (80%). The hospital anxiety and depression scale has been recorded by clinicians (75%) before and after the fabrication of obturators. Whereas, 80% out of the above reveals that the anxiety and depression among mothers have been reduced after the treatment. Conclusion: The findings of this survey with dental practitioners showed that management of feeding difficulties among orofacial cleft infants with feeding plate obturators still presents some deviations from scientific literature recommendations, indicating the need to update these health-care professionals to establish guidelines for postnatal dental care. [ABSTRACT FROM AUTHOR]

The objective was to present an optimized imaging protocol for orofacial cleft (OFC) patients, which might be used as an international recommendation for OFC care programs. The present radiological protocol has been structured by the OFC team of the University Hospitals Leuven based on a combined approach of clinical experience and scientific evidence. The development was based on careful monitoring of the existing needs for radiological diagnosis by the involved disciplines. Needs were revised by expert consensus and radiological optimization. Effective doses were converted to panoramic equivalents (professional conversion) and background radiation (patient conversion). At the age of 6, a panoramic radiograph is taken for the evaluation of dental anomalies. For the preoperative planning of secondary alveolar bone, grafting a low‐resolution cone beam computer tomography (CBCT) of a limited field of the maxilla is taken at the age of 7 to 9. At the age of 10, 15, and 20, a low‐resolution CBCT of both jaws with the smallest possible field is taken serving as conventional, presurgical, and end of treatment records, respectively. Two‐dimensional images are reconstructed out of 3D ones. There are currently no international guidelines concerning the imaging protocol for OFC patients. It is clear that a multidisciplinary approach plays a key role in radiation hygiene. In this article, we presented an optimized imaging protocol for OFC patients based on European guidelines to accomplish the concepts of justification and optimization, which might be used as an international recommendation for OFC care programs. [ABSTRACT FROM AUTHOR]

Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformation worldwide, and its etiology involves both genetic and environmental factors. Recent genome-wide and targeted genetic studies of nsCL/P have identified numerous genetic risk loci, under the hypothesis of a multiplicative mode of inheritance. The present study investigated whether novel nsCL/P risk loci could be identified by analyzing dominant/recessive genetic effects in single nucleotide polymorphism (SNP) data from genome-wide association studies. For this purpose, a genome-wide investigation of dominant/recessive common SNP effects was performed in our previously published meta-analysis data set. Twenty-four loci were identified as candidate regions. In a subsequent association analysis in an independent study cohort of 224 nsCL/P patients and 986 controls of European descent, none of the loci could be replicated. Therefore, our strategy of identifying novel loci by applying different genetic models did not yield any novel findings, suggesting that recessive/dominant common variation only make a limited contribution to nsCL/P in Europeans. However, we cannot rule out that such effects are present at some of the loci that have previously been identified, or are present in different populations. [ABSTRACT FROM AUTHOR]

We report a case of a 6-month-old male that presented with wound dehiscence, in part due to mechanical tongue trauma, following bilateral cleft lip repair. A silastic sheeting dressing with retention sutures was uniquely fashioned to decrease wound tension and protect the surgical site from patient interference. This solution may potentially be used in similar circumstances. [ABSTRACT FROM AUTHOR]

Objective: Methyleneterahydrofolate reductase (MTHFR) A1298C polymorphism has been reported a risk factor for nonsyndromic cleft/palate (NSCL/P) in several published articles but results were inconclusive. To confirm the association between maternal MTHFR A1298C polymorphism and NSCL/P risk, a meta-analysis was conducted. Method: Case control articles for maternal MTHFR A1298C polymorphism and NSCL/P risk were identified by search of databases including PubMed, Google Scholar, Elsevier and Springer Link for the period up to December, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: Meta-analysis of ten included studies showed that there was no significant association between maternal MTHFR A1298C polymorphism and risk of NSCL/P under five genetic models (for C versus A, OR= 1.007, 95 % CI= 0.89-1.13, P=0.90; for CC versus AA, OR=0.851, 95 % CI = 0.63-1.15, P=0.30.; for AC versus AA, OR= 1.033, 95 % CI= 0.88-1.21, P= 0.69; for CC+AC versus AA, OR= 1.005, 95 % CI= 0.86-1.17, P=0.94; for CC versus AC+AA, OR= 0.86, 95 % CI= 0.64-1.15, P= 0.32). Conclusion: In conclusion, results of present meta-analysis demonstrate that maternal MTHFR A1298C polymorphism may not be a risk factor for developing NSCL/P in offspring. Further studies with large sample sizes are needed to evaluate the association of maternal MTHFR A1298C polymorphism with NSCL/P in more detail.

The etiology of orofacial cleft as Non-syndromic cleft lips with or without palate (NSCL/P) are complex which including genetic and environmental factors. To investigate maternal polymorphism of MTHFR C677T, A1298C and MSX1as the risk factor of NSCL/P in Sasak Tribe, Lombok Indonesia. The study was a case control study involving 148 subjects from Sasak Tribe, consisting of 35 children with NSCL/P-mother pairs and 39 healthy children-mother pairs as controls. EDTA blood was drawn from all subjects. Molecular analyses of MTHFR C677T, A1298C and MSX1 polymorphisms were done using PCR-RFLP. The risk factors were analyzed statistically using OR and Chi square test. Children with at least one copy of the MTHFR 1298C allele had a higher risk of NSCL/P (p=0.036, OR 2.7, 95% CI (1.1-7.0)). Maternal polymorphisms MTHFR C677T and MSX1 were not found to be risk factors of NSCL/P (p>0.05). New sequence variation of c.469 + 12G>A was found near the splice site region of exon 1 MSX1 in an affected child. MTHFR A1298C polymorphism increases the risk of NSCL/P in Sasak Tribe, Lombok, Indonesia. A novel sequenceof MSX1 c.469 + 12G>A was found. Further study with higher sample size to fullfill minimum number of subjects for genetic study may found more new novel polymorphisms. [ABSTRACT FROM AUTHOR]

Objective: To investigate the evolution of maternal representations (ie, the way parents perceive their child in term of temperament, character, behaviors, etc) of children with a cleft at 3 major milestones: before/after reconstructive surgeries and at school age. Parenting style was also analyzed and compared with parents of children born without a cleft. Objective: To investigate the evolution of maternal representations (ie, the way parents perceive their child in term of temperament, character, behaviors, etc) of children with a cleft at 3 major milestones: before/after reconstructive surgeries and at school age. Parenting style was also analyzed and compared with parents of children born without a cleft. Design and participants: The sample was composed of 30 mothers of children with an orofacial cleft and 14 mothers of children without a cleft. Maternal representations were assessed when the child was 2 months (before surgery), 12 months (after surgery), and 5 years of age (when starting school) using semistructured interviews that were transcribed and coded according to the subscales of the Working Model of the Child Interview and the Parental Development Interview. At the 5-year appointment, mothers also completed a questionnaire about parenting style. Results: Results showed no difference across groups (cleft/noncleft) in maternal representations at the 2-month, 12-month, and 5-year assessments. In the cleft group, significant differences were shown between 2 and 12 months in caregiving sensitivity, perceived infant difficulty, fear for the infant's safety, and parental pride, all factors being higher at 12 months. Those differences in parental representations over time were not found in the noncleft group. Additionally, mothers of the cleft group were significantly more authoritarian than mothers of children without a cleft. Conclusion: The absence of differences across cleft and noncleft groups suggests that having a child with a cleft does not affect maternal representations and emotions between 2 months and 5 years of the child's age. However, parenting style seems to be influenced by the presence of a cleft in the present sample. [ABSTRACT FROM AUTHOR]

Oral clefts play an essential role in disturbed odontogenesis of the deciduous and permanent dentition, yet little is known about this relationship. We investigated, within the categories cleft lip with or without alveolus (CL ± A) and cleft lip, alveolus and palate (CLAP), whether different CL subphenotypes based on morphological severity of the cleft show different dentition patterns and whether a more detailed subdivision of the incomplete CL has clinical relevance. In this retrospective study, 345 children with nonsyndromic unilateral CL ± A and CLAP from the Dutch Association for Cleft Palate and Craniofacial Anomalies (NVSCA) registry were included to assess the association between the CL subphenotypes and lateral incisor patterns. Five different deciduous and permanent patterns of the lateral incisor were distinguished: located in normal position (pattern z/Z), in the anterior segment (pattern x/X) or in the posterior segment of the cleft (pattern y/Y), one in each segment of the cleft (pattern xy/XY), and agenesis of the lateral incisor (pattern ab/AB). Analyses were performed by using multinomial logistic regression models. Children born with a vermillion notch or a one-third to two-thirds CL were most likely to have a deciduous pattern x and a permanent pattern X, while children born with a two-thirds to subtotal CL were most likely to have deciduous pattern xy and a permanent pattern X compared to children with a complete CL that predominantly had deciduous pattern y and a permanent pattern AB. Based on the relationship of the CL morphology with the deciduous dentition, subdivision of the CL morphology into vermillion notch to two-thirds CL, two-thirds to subtotal CL, and complete CL appears to be an optimal subdivision. Our results indicate that a more detailed subdivision of the CL has clinical relevance and that critical factors in the pathogenesis of the CL are also critical for the odontogenesis. [ABSTRACT FROM AUTHOR]

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Background Orofacial clefts (OFCs), including nonsyndromic cleft lip with or without cleft palate (NSCL/P), are common birth defects. NSCL/P is highly heterogeneous with multiple phenotypic presentations. Two common subtypes of NSCL/P are cleft lip (CL) and cleft lip with cleft palate (CLP) which have different population prevalence. Similarly, NSCL/P can be divided into bilateral and unilateral clefts, with unilateral being the most common. Individuals with unilateral NSCL/P are more likely to be affected on the left side of the upper lip, but right side affection also occurs. Moreover, NSCL/P is twice as common in males as in females. The goal of this study is to discover genetic variants that have different effects in case subgroups. Methods We conducted both common variant and rare variant analyses in 1034 individuals of Asian ancestry with NSCL/P, examining four sources of heterogeneity within CL/P: cleft type, sex, laterality, and side. Results We identified several regions associated with subtype differentiation: cleft type differences in 8q24 ( p = 1.00 × 10−4), laterality differences in IRF6, a gene previously implicated with wound healing ( p = 2.166 × 10−4), sex differences and side of unilateral CL differences in FGFR2 ( p = 3.00 × 10−4; p = 6.00 × 10−4), and sex differences in VAX1 ( p < 1.00 × 10−4) among others. Conclusion Many of the regions associated with phenotypic modification were either adjacent to or overlapping functional elements based on ENCODE chromatin marks and published craniofacial enhancers. We have identified multiple common and rare variants as potential phenotypic modifiers of NSCL/P, and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs. Birth Defects Research 109:1030-1038, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The 'missing' heritability may be found in rare variants, copy number variants, or interactions. In this study, we investigated the role of low-frequency variants genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip. We performed two statistical tests, Sequence Kernel Association Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the transcription factor TP63 gene cause a variety of clinical phenotypes, such as ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome. Historically, TP63 -related phenotypes have been divided into several syndromes based on both the clinical presentation and location of the pathogenic variant on the TP63 gene. This division is complicated by significant overlap between syndromes. Here we describe a patient with clinical characteristics of different TP63 -associated syndromes (cleft lip and palate, split feet, ectropion, erosions of the skin and corneas), associated with a de novo heterozygous pathogenic variant c.1681 T>C, p.(Cys561Arg) in exon 13 of the TP63 gene. Our patient also developed enlargement of the left-sided cardiac compartments and secondary mitral insufficiency, which is a novel finding, and immune deficiency, which has only rarely been reported. The clinical course was further complicated by prematurity and very low birth weight. We illustrate the overlapping features of EEC and AEC syndrome and multidisciplinary care needed to address the various clinical challenges. [ABSTRACT FROM AUTHOR]

Craniofacial development is a complex and tightly regulated process and disruptions can lead to structural birth defects, the most common being nonsyndromic cleft lip and palate (NSCLP). Previously, we identified FOS as a candidate regulator of NSCLP through family-based association studies, yet its specific contributions to oral and palatal formation are poorly understood. This study investigated the role of fos during zebrafish craniofacial development through genetic disruption and knockdown approaches. Fos was expressed in the periderm, olfactory epithelium and other cell populations in the head. Genetic perturbation of fos produced an abnormal craniofacial phenotype with a hypoplastic oral cavity that showed significant changes in midface dimensions by quantitative facial morphometric analysis. Loss and knockdown of fos caused increased cell apoptosis in the head, followed by a significant reduction in cranial neural crest cells (CNCCs) populating the upper and lower jaws. These changes resulted in abnormalities of cartilage, bone and pharyngeal teeth formation. Periderm cells surrounding the oral cavity showed altered morphology and a subset of cells in the upper and lower lip showed disrupted Wnt/β-catenin activation, consistent with modified inductive interactions between mesenchymal and epithelial cells. Taken together, these findings demonstrate that perturbation of fos has detrimental effects on oral epithelial and CNCC-derived tissues suggesting that it plays a critical role in zebrafish craniofacial development and a potential role in NSCLP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maili, Tandon, Yuan, Menezes, Chiu, Hashmi, Letra, Eisenhoffer and Hecht.)

OBJETIVO: Fissura labial com ou sem fissura palatina (FL ± P) ou fissura palatina (FP) são grupos de malformações chamados fissuras orofaciais (FO) e são a segunda causa de defeitos congênitos. O objetivo do estudo foi analisar características clínicas e epidemiológicas de pacientes brasileiros com FO, estudando casos tratados no centro de referência do estado do Paraná (PR). MÉTODOS: Foram analisados 2.356 gráficos. Destes, 1.838 foram avaliados pelo mesmo geneticista clínico. Os dados foram coletados no centro de referência e analisados na Secretaria de Estado da Saúde do Paraná. Foram avaliadas as características clínicas, a presença de outras anomalias e a prevalência de nascimentos. RESULTADOS: No total, 389 (21,2%) pacientes apresentaram fissura palatina (FP), 437 (23,8%) apresentaram fissura labial (FL) e 1.012 (55%) apresentaram fissura labiopalatina (FLP). As FO sindrômicas foram identificadas em 15,3% dos pacientes, 10,4% dos pacientes com FL ± P, e 33,9% dos pacientes com FP. Anomalias comuns adicionais foram: sistema nervoso central, membros, sistema cardiovascular e sistema musculoesquelético. O número de casos sindrômicos foi menor nos centros em que a avaliação clínica foi realizada por outros especialistas, em comparação aos locais em que ela foi realizada por um geneticista clínico. A prevalência de nascimentos foi de 1/1.010 nascidos vivos. A ausência de notificação junto ao cartório de registro civil foi observada em 49,9% dos casos de FL ± P. No Brasil, nossos dados sugerem uma redução de 18,52% na prevalência de FO não sindrômicas após a fortificação com ácido fólico. CONCLUSÃO: Um melhor entendimento dos aspectos clínicos e epidemiológicos das FO é fundamental para melhorar a compreensão de sua patogênese, promover estratégias de prevenção e promover orientações com relação a cuidados clínicos, com a presença de geneticistas clínicos na equipe multidisciplinar para tratamento de FO, por exemplo.OBJECTIVE: Cleft lip with or without cleft palate (CL±P) or cleft palate (CP) are groups of malformations named orofacial clefts (OC), which are the second leading cause of birth defects. This study aimed to analyze clinical and epidemiological features of Brazilian patients with OC, studying cases treated in the reference center of the state of Paraná (PR). METHODS: 2,356 charts were reviewed and 1,838 were evaluated by the same clinical geneticist. Data were collected in the reference center, and compared with those of the Health Department of the state of Paraná. Clinical characteristics, presence of other anomalies, and birth prevalence were evaluated. RESULTS: 389 (21.2%) patients had CP, 437 (23.8%) had cleft lip (CL), and 1,012 (55%) had cleft lip and palate (CLP). Syndromic OC were identified in 15.3% of patients, 10.4% of patients with CL±P, and 33.9% of patients with CP. Common additional anomalies were: central nervous system, limbs, cardiovascular, and musculoskeletal defects. The number of syndromic cases was lower when clinical evaluation was performed by other medical specialists when compared to that of the clinical geneticist. Birth prevalence was 1/1,010 live births. Lack of notification with the national birth registry was observed in 49.9% of CL±P. The present data suggests a decrease of 18.52% in the prevalence of non-syndromic OC after folic acid fortification in Brazil. CONCLUSIONS: Better understanding of clinical and epidemiological aspects of OC is crucial to improve the understanding of pathogenesis, promote preventive strategies, and guide clinical care, including the presence of clinical geneticists in the multidisciplinary team for OC treatment.

Objective: : Cleft lip with or without cleft palate (CL±P) or cleft palate (CP) are groups of malformations named orofacial clefts (OC), which are the second leading cause of birth defects. This study aimed to analyze clinical and epidemiological features of Brazilian patients with OC, studying cases treated in the reference center of the state of Paraná (PR). Methods: : 2,356 charts were reviewed and 1,838 were evaluated by the same clinical geneticist. Data were collected in the reference center, and compared with those of the Health Department of the state of Paraná. Clinical characteristics, presence of other anomalies, and birth prevalence were evaluated. Results: : 389 (21.2%) patients had CP, 437 (23.8%) had cleft lip (CL), and 1,012 (55%) had cleft lip and palate (CLP). Syndromic OC were identified in 15.3% of patients, 10.4% of patients with CL±P, and 33.9% of patients with CP. Common additional anomalies were: central nervous system, limbs, cardiovascular, and musculoskeletal defects. The number of syndromic cases was lower when clinical evaluation was performed by other medical specialists when compared to that of the clinical geneticist. Birth prevalence was 1/1,010 live births. Lack of notification with the national birth registry was observed in 49.9% of CL±P. The present data suggests a decrease of 18.52% in the prevalence of non-syndromic OC after folic acid fortification in Brazil. Conclusion: : Better understanding of clinical and epidemiological aspects of OC is crucial to improve the understanding of pathogenesis, promote preventive strategies, and guide clinical care, including the presence of clinical geneticists in the multidisciplinary team for OC treatment.