Nonsyndromic Cleft Lip Research Articles

Integrative Multi-omics Analysis Identifies Genetic Variants Contributing to Non-syndromic Cleft Lip with or without Cleft Palate.

To provide novel insights into the aetiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) by integrating multi-omics data and exploring susceptibility genes associated with NSCL/P. A two-stage genome-wide association study (GWAS) of NSCL/P was performed, involving a total of 1,069 cases and 1,724 controls. Using promoter capture Hi-C (pCHi-C) datasets in human embryonic stem cells (hESC) and chromatin immunoprecipitation sequencing (ChIP-seq) in craniofacial tissues, we filtered out single nucleotide polymorphisms (SNPs) with active cis-regulation and their target genes. Additionally, we employed expression quantitative trait loci (eQTL) analysis to identify candidate genes. Thirteen SNPs were identified as cis-regulation units associated with the risk of NSCL/P. Five of these were proven to be active in chromatin states in early human craniofacial development (rs7218002: odds ratio [OR] 1.50, P = 8.14E-08; rs835367: OR 0.78, P = 3.48E- 05; rs77022994: OR 0.55, P = 1.05E-04; rs961470: OR 0.73, P = 1.38E-04; rs17314727: OR 0.73, P = 1.85E-04). Additionally, pCHi-C and eQTL analysis prioritised three candidate genes (rs7218002: NTN1, rs835367: FGGY, LINC01135). NTN1 and FGGY were expressed in mouse orofacial development. Deficiencies in NTN1, FGGY and LINC01135 were associated with cleft palate and cleft lip, abnormal facial shape and bifid uvula, and abnormality of the face, respectively. Our study identified five SNPs (rs7218002, rs835367, rs77022994, rs961470 and rs17314727) and three susceptibility genes (NTN1, FGGY and LINC01135) associated with NSCL/P. These findings contribute to a better understanding of the genetic factors involved.

Patterns of primary and secondary defects associated with non-syndromic cleft lip and palate: An epidemiological analysis in a Kenyan population.

Cleft lip and palate deformities substantially burden individuals and families, particularly in low-income communities. However, a comprehensive understanding of the patterns and distribution of these deformities in Kenya remains limited. This retrospective cross-sectional study analyzed 647 clinical records from the BelaRisu Foundation registry in Kenya, spanning 2018-2022. After meticulous record verification and data extraction, cleft pattern modeling was used to analyze each case. Data were imported to SPSS version 29.0 and descriptive statistics were calculated, which included means, ranges, frequencies, percentages, and standard deviations. Additionally, a comparative analysis between genders was conducted. The findings revealed a higher average age of presentation compared with previous studies in Kenya, along with a greater susceptibility of males to cleft lip and palate defects overall. Noteworthy disparities in case distribution across provinces were observed. Cleft lip emerged as the most observed primary defect, while palatal fistulae constituted the most frequent secondary defect. Interestingly, while some results aligned with global trends, others diverged significantly from the existing literature, warranting further exploration and investigation. These findings shed light on the unique patterns and distribution of cleft lip and palate deformities in Kenya, highlighting the need for targeted interventions and support systems.

Detection of Single Nucleotide Polymorphism (SNP) rs2235371 of IRF6 Gene in Patients with Non-Syndromic Cleft Lip and Palate

The orofacial clefts are the most common structural birth defects among newborn babies. They consist of two groups, namely Cleft Palate (CP) and Cleft Lip (CL). Infants born with clefts have considerable problems during communication, swallowing, and face certain challenges due to facial deformity. These problems remain throughout the life if not treated and entail long-lasting effects on the health and social life of an individual. Untreated infants need special care as they have higher morbidity and mortality rates. The primary objective of this study is to detect the Single Nucleotide Polymorphism (SNP) rs2235371 within the IRF6 gene and assess its potential association in patients diagnosed with Non-Syndromic Cleft Lip/Palate (NSCL/P). The participants were selected through a non-probability sampling technique, specifically the purposive sampling method. In accordance with this approach, a total of 50 patients afflicted with NSCL/P, representing both the genders, were sampled. Furthermore, to establish a comparative baseline, an additional 50 healthy individuals were also recruited to serve as the control group. After taking their informed consent, blood was collected in EDTA vials. PCR (Polymerase Chain Reaction) and RFLP were performed on each sample to find SNP. After sample collection, processing, and analysis, SPSS (20.00 version) was used to analyze all previously generated data. After sample analysis, 72% of CL/P (cleft lip and palate) patients were found to have SNP with or without a family history. The association of SNP rs2235371 with disease was measured by applying chi-square. The results provided no evidence of the association between given SNP and disease. As compared to previous research, this study showed a low frequency of SNP rs2235371 in patients with NSCL/P. To get a better understanding of the association of SNP rs2235371 with NSCL/P, large-scale research with an increased sample size should be conducted.

Identification of a novel mutation of Platelet-Derived Growth Factor-C (PDGFC) gene in a girl with Non-Syndromic cleft lip and palate

BackgroundCleft lip with or without cleft palate (CL/CP) is a prevalent congenital malformation. Approximately 16 candidate loci for CL/CP have been identified in both animal models and humans through association or genetic linkage studies. One of these loci is the platelet-derived growth factor-C (PDGFC) gene. In animal models, a mutation in the PDGFC gene has been shown to lead to CL/CP, with PDGF-C protein serving as a growth factor for mesenchymal cells, playing a crucial role in embryogenesis during the induction of neural crest cells. In this study, we present the identification of a novel frameshift mutation in the PDGFC gene, which we hypothesize to be associated with CL/CP, within a consanguineous Iranian family. Case presentationThe proband was a 3-year-old girl with non-syndromic CL/CP. A history of craniofacial clefts was present in her family. Following genetic counseling, karyotype analysis and whole-exome sequencing (WES) were performed. Cytogenetic analysis revealed normal results, while WES analysis showed that the proband carried a homozygous c.546dupA (p.L183fs) mutation in the PDGFC gene. Sanger sequencing confirmed that her parents were carriers of the mutation. ConclusionThe c.546dupA (p.L183fs) mutation of PDGFC has not been previously reported and was not found in human genome databases. We speculate that the c.546dupA mutation of the PDGFC gene, identified in the Iranian patient, may be responsible for the phenotype of non-syndromic CL/CP (ns-CL/CP). Further studies are warranted to explore the specific pathogenesis of the PDGFC mutation in ns-CL/CP.

Prevalence of Dental Anomalies in Patients with Non-syndromic Cleft Lip with or without Cleft Palate

This study aimed to assess the prevalence and distribution pattern of dental anomalies in the permanent teeth of patients with non-syndromic cleft lip with or without cleft palate. Additionally, it aimed to compare differences in dental anomalies between cleft and non-cleft areas, considering gender and cleft phenotype. Panoramic radiographs of 164 patients diagnosed with non-syndromic orofacial clefts were retrospectively analyzed by a single examiner to confirm dental anomalies. The dental anomalies investigated included tooth agenesis, supernumerary teeth, microdontia, rotation, ectopic eruption, and enamel hypoplasia. Cleft phenotypes were categorized into 7 types based on medical and dental records. A significantly higher prevalence of supernumerary teeth was observed in males than females within non-cleft areas (<i>p</i> = 0.017), with no significant differences in other dental anomalies. In non-cleft area, patients with cleft palate exhibited a high prevalence of tooth agenesis (<i>p</i> < 0.0001) and microdontia (<i>p</i> = 0.012) compared to other cleft phenotypes. Maxillary incisor rotation was closely associated with adjacent tooth agenesis in unilateral cleft lip and palate cases (<i>p</i> = 0.034). This study suggests that the additional subphenotype based on dental anomalies in patients with orofacial cleft may serve as applicable clinical markers.

Cleft Laterality Dental Arch Relationship Outcomes for Children with Unilateral Cleft Lip and Palate in New Zealand.

To investigate cleft laterality dental arch relationship outcomes of children with non-syndromic complete unilateral cleft lip and palate (UCLP) in New Zealand. A retrospective nationwide study. Virtual 3D orthodontic study models collected prior to undertaking secondary alveolar bone grafting. A total of 104 patients with UCLP (L = 80: R = 24). Four calibrated assessors used the GOSLON Yardstick and 100 mm Visual Analogue Scale (VAS) to score the randomised models on 2 separate assessment sessions. Weighted Kappa were used to determine the intra/inter-rater reliability for the GOSLON and correlations for the VAS. Intra-rater reliability ranged from 0.57-0.88 (GOSLON) and 0.45-0.93 (VAS). Inter-rater reliability ranged from 0.62-0.86 (GOSLON) and 0.64-0.93 (VAS).GOSLON scores for the left UCLP were 31.2% for good/very good; 26.3% for fair; 42.5% for poor/very poor while the right UCLP scored 8.3% for good/very good; 37.5% for fair; 54.2% for poor/very poor. The mean VAS for left and right UCLP were 53.4 (sd 22.5) and 44.6 (sd 17.1) respectively. Neither the GOSLON nor VAS differences reached statistical significance (both P = .08). From a clinical perspective right UCLP had worse dental arch relationship outcomes, however, these differences failed to reach statistical significance. Further studies using larger sample sizes are required to determine if cleft laterality is an important consideration when investigating UCLP dental arch outcomes.

Genetic Associations of Oral Clefts in Arabs.

This study aims to investigate genetic association between Non-syndromic Cleft lip with or without palate (NCLP) and 14 specific Single Nucleotide Polymorphism (SNPs) reported to be associated with NCLP from previous Genome Wide Association Studies (GWAS). A prospective case-control study. Ministry of Health (MOH) Cleft and Craniofacial Clinic and Kuwait University. One hundred sixty-four NCLP patients were recruited from MOH Cleft and Craniofacial clinic, and 491 controls from the Kuwait DNA bank established at Kuwait University. Total gDNA was extracted from whole blood withdrawn from patients and genotyped by real time PCR. Hardy-Weinberg Equilibrium was tested, and the set p value for significance (p < 0.05) was adjusted using the Benjamini - Hoochberg procedure to achieve 5% false discovery rate. Logistic regression multivariate analysis was used to test statistically significant differences between cases and controls. Genotyping both groups for the variants was determined through the allele discrimination software program. There was statistically significant difference between cases and controls in relation to two SNPs; LOC102724968 (rs13041247) (MAF cases/control = C (0.28/0.39) OR Homozygous = 1.30; 95% CI = 1.09-1.56, p = 0.0041) and PVT1 (rs987525) (MAF cases/control = A (0.41/0.27) OR heterozygous = 1.48; 95% CI =1.12-1.95, p = 0.0073), increasing the susceptibility to NCLP. Genetic variations are associated with the occurrence of oral clefts. Customized Next Generation Sequencing (NGS) panel to the Arab ethnicity is encouraged. In Addition, national preconception genetic carrier screening tests should expand to include common craniofacial anomalies.

Detecting Gene-Gene Interaction among DNA Repair Genes in Chinese non-Syndromic Cleft lip with or Without Palate Trios.

The objective of this study is to investigate the gene-gene interactions associated with NSCL/P among DNA repair genes. This study included 806 NSCL/P case-parent trios from China. Quality control process was conducted for genotyped single nucleotide polymorphisms (SNPs) located in six DNA repair genes (ATR, ERCC4, RFC1, TYMS, XRCC1 and XRCC3). We tested gene-gene interactions with Cordell's method using statistical package TRIO in R software. Bonferroni corrected significance level was set as P = 4.24 × 10-4. We also test the robustness of the interactions by permutation tests. Not applicable. A total of 806 NSCL/P case-parent trios (complete trios: 682, incomplete trios: 124) with Chinese ancestry. Not applicable. Not applicable. A total of 118 SNPs were extracted for the interaction tests. Fourteen pairs of significant interactions were identified after Bonferroni correction, which were confirmed in permutation tests. Twelve pairs were between ATR and ERCC4 or XRCC3. The most significant interaction occurred between rs2244500 in TYMS and rs3213403 in XRCC1(P = 8.16 × 10-15). The current study identified gene-gene interactions among DNA repair genes in 806 Chinese NSCL/P trios, providing additional evidence for the complicated genetic structure underlying NSCL/P. ATR, ERCC4, XRCC3, TYMS and RFC1 were suggested to be possible candidate genes for NSCL/P.

Dental Arch Relationships of Saudi Children with Unilateral Cleft Lip and Palate.

To determine dental arch relationships of Saudi children born with nonsyndromic complete unilateral cleft lip and palate (UCLP). This is a retrospective cohort study that comprised dental study models of 74 UCLP Saudi children aged 8-10 years who were recruited from 14 referral cleft centers. All participants had their cleft lip and palate repaired with no history of alveolar bone graft or any orthodontic treatment. Dental arch relationships of UCLP patients were assessed using the Great Ormond Street, London, and Oslo (GOSLON) Yardstick-a clinical tool that categorizes dental relationships of UCLP children into five discrete grades from I to V. The reliability of the rating was assessed with weighted kappa (κ) statistics. Three children (4.1%) had excellent surgical outcomes (grade I), 18 children (24.3%) filled into grade II (good outcome), 22 subjects (29.7%) had grade III (fair outcome), 27 children (36.5%) had grade IV (poor outcome), and 4 subjects (5.4%) were ranked as having very poor outcomes (grade V). The mean GOSLON score was 3.39. Intrarater and interrater agreements were high indicating good reproducibility. Based on the dental arch relationships, the treatment outcome of UCLP Saudi children was unsatisfactory, with a mean GOSLON score of 3.39. Delayed palate repair and the use of presurgical orthopedics may be considered in the future for cleft deformity management. To address the effect of particular cleft surgical protocol on dental arch relationships of UCLP patients. How to cite this article: Alforaidi S, Zreaqat M, Hassan R. Dental Arch Relationships of Saudi Children with Unilateral Cleft Lip and Palate. J Contemp Dent Pract 2023;24(12):987-990.

Effects of nasoalveolar molding on nasolabial aesthetics in patients with cleft lip and palate during pre-adolescence: A systematic review and meta-analysis of retrospective studies.

This study aims to analyze long-term effects of nasoalveolar molding (NAM) as a part of cleft primary management protocols on nasolabial aesthetics for patients with non-syndromic cleft lip and palate by conducting a systematic review and meta-analysis. Six electronic databases and two journals were searched up to July 2023. Studies comparing nasolabial outcomes between NAM and non-NAM protocols were selected for further analysis. Nasolabial aesthetics were the outcome of interest. Data extraction, methodological quality assessment, risk of bias assessment, meta-analysis and subgroup analysis were performed. Seven retrospective cohort studies were selected for a qualitative review and four for a quantitative analysis. The risk of bias assessment was moderate for most studies. Only studies utilizing the Asher-McDade rating (AMR) were included for meta-analyses. The protocols with NAM exhibited a significantly lower AMR score for vermillion border than other protocols. AMR scores for nasal form and nasal symmetry from protocols with NAM were significantly lower than protocols without any pre-surgical infant orthopaedics (PSIO) but not significantly different from protocols with other PSIO techniques. The AMR score for nasolabial profile from protocols with NAM was not significantly different from other protocols. However, subgroup analysis demonstrated that protocol combining NAM and primary rhinoplasty significantly lowered AMR scores for nasal form, nasal symmetry and nasolabial profile. For patients with unilateral cleft lip with or without palate (UCLP), this study found that a protocol combining NAM and primary rhinoplasty improved nasolabial outcomes while a protocol with NAM alone offered only limited benefits. For patients with BCLP, the available evidence remains inconclusive. Performing NAM in combination with primary rhinoplasty improves nasolabial aesthetics in patients with UCLP. PROSPERO (CRD4202128384).

Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = − 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = − 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.

Should left- and right-sided unilateral cleft lip and palate patients be grouped together when reporting the outcomes?

Investigate associations between cleft laterality in patients with non-syndromic unilateral cleft lip and palate (UCLP) and oral-health, dental-arch, speech, audiological, psychological and nasolabial-aesthetic outcomes. Secondary data analysis of the outcomes of 5-year-old children with non-syndromic complete UCLP identified from three studies: Cleft Collective (n = 155), Cleft Care UK (CCUK) (n = 266) and Clinical Standards Advisory Group (CSAG) study (n = 238). Outcome measures included occlusal assessment using the 5-year-old's index score, speech intelligibility rating using the CAPS-A Audit tool, audiological assessment using pure tone audiometry, nasolabial aesthetic assessment using the Asher-McDade tool, oral-health assessment using decayed, missing, filled teeth scores and parent-reported outcomes. Logistic regression with adjustment for age, sex and index-of-multiple-deprivation scores were performed. No differences were found in patient-reported outcomes between the left and right clefts in the Cleft Collective study. From the CCUK study, right clefts had poorer speech (n = 236; 95% CI 1.09, 3.42; and P = .03) and hearing outcomes (n = 211; 95% CI 1.03, 3.43; P = .04). In the CSAG study, patients with left clefts were more likely to be teased (n = 213; 95% CI 0.26, 0.85; and P = .01). Weak associations between cleft laterality, speech, hearing and psychological outcomes were found, however the findings were inconsistent across the studies. This study contributes to evidence of associations between laterality and outcomes in children born with UCLP.

Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021

BackgroundsCleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors.Methods and materialsIn this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling.ResultsThe total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79–4.97), for both sexes, and 5.96 (5.82–6.10) for males, and 3.75 (3.64–3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01–1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33–1.60, p < 0.001), mothers with extreme obesity (OR = 1.32, 1.21–1.43, p < 0.001), mothers with grade II obesity (OR = 1.32, 1.23–1.42, p < 0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04–1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71–2.25, p < 0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18–1.66, p < 0.001).ConclusionsOur findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Dental Anomalies and Muscle Segment Homeobox1 Gene Polymorphism in Non-syndromic Cleft Lip with or without Palate Children

This study aims to determine the prevalence of dental anomalies and MSX1 gene 799G&gt;T polymorphism and its association with non-syndromic cleft lip with or without palate (NSCL±P) attending Hospital Universiti Sains Malaysia. Clinical and radiological assessments on 37 NSCL±P patients and 80 non-cleft children were done to detect dental anomalies. The buccal cells were collected and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to identify polymorphism. NSCL±P was higher among males (54%) and mostly unilateral cleft lip and palate (51.3%). The prevalence of dental anomalies in morphology in NSCL±P was 18.9% (95% CI: 5.7%, 32.2%) and non-cleft was 6.3% (95% CI: 0.8%, 11.7%). Hypodontia in NSCL±P was 75% (95% CI: 61.2%, 90.2%) and non-cleft was 7.5% (95% CI: 1.6%, 13.4%). There was a significant association between NSCL±P and anomalies in morphology (P= 0.04; OR=3.5)) and number (P&lt; 0.01; OR= 40). There was an absence of rare 799G&gt;T polymorphism in all NSCL±P and non-cleft children indicating that all samples contain common 799G polymorphism. In conclusion, the prevalence of dental anomalies in morphology and number was significantly higher in NSCL±P compared to non-cleft children. However, it was not significantly associated with MSX1 799G&gt;T polymorphism.

Effectiveness of pre-alveolar bone graft orthodontics for patients with non-syndromic complete unilateral cleft lip, alveolus and palate: A systematic review and meta-analysis.

Non-syndromic complete unilateral cleft lip, alveolus and palate patients who have had ABG surgery. Orthodontics prior to ABG. Comparison: No orthodontic treatment prior to ABG. Successful eruption of permanent canines. All articles were screened for the title, abstract and full text independently and in duplicate by 2 reviewers. The quality assessment of RCT was performed using Cochrane's risk of bias tool and the CCT was assessed using ROBINS-I tool. Of the 904 studies retrieved in the search, one RCT and one CCT were included. Both studies were judged as high risk of bias. The results from one study showed a statistically significant increase in bone volume and decreased bone defect post-ABG in the orthodontic treatment group. However, there was no difference with respect to other variables. Both included studies were of low quality. There is not enough evidence to recommend orthodontic treatment pre-ABG for patients with complete unilateral cleft lip, alveolus and palate. Future high-quality studies are required to inform patients and clinicians about the effectiveness of pre-graft orthodontic treatment.

Speech in 7- and 10-year-olds born with a unilateral cleft lip and palate: a continued prospective Swedish intercentre study.

The aim of this study was to report longitudinal speech results in consecutively selected children from each of the six cleft centres in Sweden and to compare the results between centres. The children were born with a non-syndromic unilateral cleft lip and palate, and results from the same cohort at 5 years of age have previously been reported. Background data on medical care in terms of surgery, speech therapy, and hearing between 5 and 10 years of age were collected. Speech recordings of 56 children at 7 years and 54 at 10 years of age were blindly and independently assessed by four speech-language pathologists experienced in cleft palate speech. This resulted in measures of percent consonant correct (PCC) and perceived velopharyngeal competence rated on a three-tier scale. No statistically significant differences were found between centres. PCC scores at 7 years of age ranged from 44-100% (median 97.5) and at 10 years of age from 86-100% (median 100). Competent or marginally incompetent velopharyngeal function was found in 95% of the 7-year-olds and 98% of the 10-year-olds. Speech results were slightly better than previous reports of speech in children born with a unilateral cleft lip and palate.

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

BackgroundNonsyndromic cleft lip and/or without cleft palate (NSCL/P) with or without hypodontia is a common developmental aberration in humans and animals. This study aimed to identify the loss of heterozygosity (LOH) involved in hypodontia and NSCL/P pathogenesis.MethodsThis is a cross-sectional study that conducted genome-wide copy number analysis using CytoScan 750K array on salivary samples from Malay subjects with NSCL/P with or without hypodontia aged 7–13 years. To confirm the significant results, simple logistic regression was employed to conduct statistical data analysis using SPSS software.ResultsThe results indicated the most common recurrent copy neutral LOH (cnLOH) observed at 1p33-1p32.3, 1q32.2-1q42.13 and 6p12.1-6p11.1 loci in 8 (13%), 4 (7%), and 3 (5%) of the NSCL/P subjects, respectively. The cnLOHs at 1p33-1p32.3 (D1S197), 1q32.2-1q42.13 (D1S160), and 6p12.1-6p11.1 (D1S1661) were identified observed in NSCL/P and noncleft children using microsatellite analysis markers as a validation analysis. The regions affected by the cnLOHs at 1p33-1p32.3, 1q32.2-1q42.13, and 6p12.1-6p11.1 loci contained selected genes, namely FAF1, WNT3A and BMP5, respectively. There was a significant association between the D1S197 (1p33-32.3) markers containing the FAF1 gene among NSCL/P subjects with or without hypodontia compared with the noncleft subjects (p-value = 0.023).ConclusionThe results supported the finding that the genetic aberration on 1p33-32.3 significantly contributed to the development of NSCL/P with or without hypodontia. These results have an exciting prospect in the promising field of individualized preventive oral health care.

MSX1 Gene Polymorphisms in Patients with non-Syndromic Cleft lip and Palate: A Tertiary Care Centre Based Case-Control Study from Central Kerala

Objective The purpose of this study was to investigate the contribution of MSX1 gene polymorphisms to the risk of developing NSCLP. Design Case-Control Study. Setting A tertiary care centre. Patients/Participants The sample consisted of 200 subjects (100 cases and 100 controls). Interventions None. Main Outcome Measure(s) Genotyping was performed by restriction fragment length polymorphism. Allele and genotype frequencies were calculated between patients and controls and analyzed using online Web Tools such as SISA and SNPstats. The MSX1 gene polymorphisms c. 799 GT, c.458 CA can be risk factors in the development of orofacial clefts. Results In the cases, an association was found between NSCLP and c.799 and c.458 of the MSX1 gene when compared with the control. The dominant and overdominant models, c. 799 GT, c.458 CA genotypes and c. 799 T, c.458 A alleles in the population are said to be the main risk factors to develop the NSCLP in our study population. The genotype variation of c 799 G/T and c.458 C/A are revealed to be specifically contributing to an NSCLP-type Cleft lip and Palate. It is worth noting that NSCLP females in the study population showed a stronger association with heterozygous genotypes of c.799 and c.458. However, further investigation with a larger cohort is necessary to confirm these findings. Conclusion Overall the results of the study revealed that MSX1 c 799 G &gt; T and c.458 C &gt; A can be considered as one of the genetic risk factors in the formation of Non-Syndromic Cleft Lip and Palate in the study population.

Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.

This study aims to identify potential variants in the TP63-IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case-parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case-control analyses, and family-based association tests for case-parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL/P) in the G allele, with pallele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375-rs846810 of IRF6 impacted NSCL/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL/P, and haplotypes G-G and C-A at rs2235375-rs846810 of IRF6 associated with NSOFC.

Cleft lip and palate risk factors among otorhinolaryngology: Head and neck surgery patients in two hospitals.

Cleft lip and/or palate is the most prevalent type of head and neck deformity, accounting for 65% of cases. The occurrence of this condition is influenced by both genetic and environmental factors. Cleft defects are classified into 2 types: syndromic cleft lip and palate syndrome and non-syndromic cleft lip and palate syndrome. Cleft lip with or without cleft palate is the most common type of cleft defect, and the surgical repair is the primary treatment option for patients. Our study was a retrospective case-control study that included 132 cases of patients with cleft defects and 132 healthy babies without cleft defects serving as controls. Personal information, including the name, age, and origin of the participants, was collected. Additionally, we collected information on all potential risk factors, including medical history, daily habits, consanguinity between parents, and family history. Information was collected in Excel and analyzed using the Statistical Package for Social Sciences and a Chi-Square test was performed to determine the results and their relationship to cleft lip and palate. Our study identified various risk factors that have a significant association with cleft lip and palate with a P-value <5% in addition to factors that are not considered risk factors. Using relative risk analysis, we were able to rank the top 5 most significant and influential risk factors. The most impactful factor was not taking folic acid during pregnancy. The primary risk factors associated with cleft lip and palate include a family history of the condition, lack of folic acid supplementation, maternal age over 35 years, and high temperatures exceeding 39 °C. Consequently, we recommend that mothers who intend to conceive should take folic acid supplements at a dose of 0.4 to 0.8 mg during the initial trimester of pregnancy. Additionally, we advise careful monitoring of all risk factors, particularly during the first trimester of pregnancy.