Shared genetic risk between major orofacial cleft phenotypes in an African population.

Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.

Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research.

BACKGROUND: A fundamental ethical issue in African genomics research is how socio-cultural factors impact perspectives, acceptance, and utility of genomic information, especially in stigmatizing conditions like orofacial clefts (OFCs). Previous research has shown that gatekeepers (e.g., religious, political, family or community leaders) wield considerable influence on the decision-making capabilities of their members, including health issues. Thus, their perspectives can inform the design of engagement strategies and increase exposure to the benefits of genomics testing/research. This is especially important for Africans underrepresented in genomic research. Our study aims to investigate the perspectives of gatekeepers concerning genomic risk information (GRI) in the presence of OFCs in a sub-Saharan African cohort. METHODS: Twenty-five focus group discussions (FGDs) consisting of 214 gatekeepers (religious, community, ethnic leaders, and traditional birth attendants) in Lagos, Nigeria, explored the opinions of participants on genomic risk information (GRI), OFC experience, and the possibility of involvement in collaborative decision-making in Lagos, Nigeria. Transcripts generated from audio recordings were coded and analyzed in NVivo using thematic analysis. RESULTS: Three main themes-knowledge, beliefs, and willingness to act-emerged from exploring the perspective of gatekeepers about GRI in this group. We observed mixed opinions regarding the acceptance of GRI. Many participants believed their role is to guide and support members when they receive results; this is based on the level of trust their members have in them. However, participants felt they would need to be trained by medical experts to do this. Also, religious and cultural beliefs were crucial to determining participants' understanding of OFCs and the acceptance and utilization of GRI. CONCLUSIONS: Incorporating cultural sensitivity into public engagement could help develop appropriate strategies to manage conflicting ideologies surrounding genomic information in African communities. This will allow for more widespread access to the advances in genomics research in underrepresented populations. We also recommend a synergistic relationship between community health specialists/scientists, and community leaders, including spiritual providers to better understand and utilize GRI.

Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes.

Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and CLP separately. A sample of 2218 CL and CLP cases, 4537 unaffected relatives of cases, and 2673 pure controls with no family history of OFC were selected from the Pittsburgh Orofacial Cleft (Pitt-OFC) multiethnic study.genome-wide association studies were run for seven specific phenotypes created based on the cleft type(s) observed within these families, as well as the combined CL/P phenotype. Five novel genome-wide significant associations, 3q29 (rs62284390), 5p13.2 (rs609659), 7q22.1 (rs6465810), 19p13.3 (rs628271), and 20q13.33 (rs2427238), and nine associations (p ≤ 1.0E-05) within previously confirmed OFC loci-PAX7, IRF6, FAM49A, DCAF4L2, 8q24.21, ARID3B, NTN1, TANC2 and the WNT9B:WNT3 gene cluster-were observed. We also found that single nucleotide polymorphisms within a subset of the associated loci, both previously known and novel, differ substantially in terms of their effects across cleft- or family-specific phenotypes, indicating not only etiologic differences between CL and CLP, but also genetic heterogeneity within each of the two OFC subtypes.

Pediatric Surgical Waitlist in Low Middle Income Countries During the COVID-19 Pandemic.

INTRODUCTION: Coronavirus disease-19 led to a significant reduction in surgery worldwide. Studies, however, of the effect on surgical volume for pediatric patients in low-income and middle-income countries (LMICs) are limited. METHODS: A survey was developed to estimate waitlists in LMICs for priority surgical conditions in children. The survey was piloted and revised before it was deployed over email to 19 surgeons. Pediatric surgeons at 15 different sites in eight countries in sub-Saharan Africa and Ecuador completed the survey from February 2021 to June 2021. The survey included the total number of children awaiting surgery and estimates for specific conditions. Respondents were also able to add additional procedures. RESULTS: Public hospitals had longer wait times than private facilities. The median waitlist was 90 patients, and the median wait time was 2 mo for elective surgeries. CONCLUSIONS: Lengthy surgical wait times affect surgical access in LMICs. Coronavirus disease-19 had been associated with surgical delays around the world, exacerbating existing surgical backlogs. Our results revealed significant delays for elective, urgent, and emergent cases across sub-Saharan Africa. Stakeholders should consider approaches to scale the limited surgical and perioperative resources in LMICs, create mitigation strategies for future pandemics, and establish ways to monitor waitlists on an ongoing basis.

Achieving a robust mentoring and research capacity program in a LMIC - the BRAINS faculty development model.

BACKGROUND: A research and training program (RTP) was carried out to build the capacity of faculty and improve the culture of research in the College of Medicine, University of Lagos (CMUL), Nigeria. METHODS: Realist-guided mixed methods evaluation of the BRAINS project was carried out using secondary data generated during the 5-years (2015 - 2020) of project implementation. Capacity building workshops and mentored research activities targeted at faculty in the CMUL were conducted. Overall, 1,418 participants attended the workshops in batches. Among the participants, forty-five faculty received grants and were mentored by senior professionals (local & international) to conduct research. Data were extracted from all project-related documents including coursework biodata, workshop evaluation forms, quarterly project reports, and end- of-project reports, submitted by the mentees, minutes of meetings, and the proposal submitted for funding. It was in the form of continuous variables and prose (sentences & stories). Quantitative data were analysed with IBM SPSS statistics version 20. Mean knowledge score and mean difference was calculated, paired t-test was carried out using p < 0.05 to determine statistical significance. The prose was thematically analysed to generate themes and narratives. Both were subsequently combined for interpretation and used to refine the initial programme theory into an evidence-informed theory. RESULTS: Twelve courses were deployed, and 1,418 participants (47.8% males and 52.2% females) from medical, nursing, and allied medical departments were trained. Eighty participants were trained in Responsible Conduct of Research and eighty-one on Manuscript Writing over three years. A comparison of the pre/post-test knowledge scores showed a positive mean difference. Thematic analysis of workshop data produced three thematic domains representing effectiveness and gains namely: cognitive, reward, and behavioural. 45 trainees were awarded grants and mentored, and analysis of mentee's data generated 4 themes: Achieving a robust mentoring program; Benefits of the mentoring program; Resilience in research; Improving the mentoring program. CONCLUSION: By contributing to the body of knowledge available on RTPs, this evaluation identified key components that contributed to the success of the project and developed a model for achieving a robust training and mentoring program which can be replicated in other LMICs.

Wound Healing Following Palatoplasty Using Either Honey or Warm Saline Mouth Bath for Postoperative Wound Care: A Randomized-Controlled Study.

OBJECTIVE: To evaluate and compare the effect of honey or saline mouth bath for wound care on the rate of re-epithelisation of the lateral palatal defects and occurrence of early postoperative complications following palatoplasty. METHODOLOGY: This was a prospective randomized study on participants with non-syndromic cleft palate conducted at a tertiary health institution in Lagos, Nigeria. The test group received oral honey drops for post-operative care for an initial period of two weeks post-surgery, while the control group had regular oral toileting using a warm saline solution. The primary outcome was epithelisation of lateral palatal defect at 2- and 4-weeks post repair. Descriptive and comparative statistics were computed, and the p-value was set at <0.05. RESULTS: Fifty participants were recruited into the study, 24 in the Test group and 26 in the Control group. The frequency of occurrence of oronasal fistula in the Test group was 4.0% while in the Control group was 10.0%, however, this was not statistically significant. Complete epithelisation of the lateral palatal defect was clinically observed in 66.7% of the participants in the Test group at 2 weeks post-operation, while only 38.5% of participants in the Control group had clinically observed complete epithelisation at the same time point (ß = 1.70, p = .035, 95% CI 1.122-26.533). At four weeks, all wounds had epithelised irrespective of the study group. CONCLUSION: The application of honey appears to aid earlier epithelization of palatal surgical wounds following cleft palate repair and reduced the incidence of palatal fistula.

A Review of the Use of Buccal Fat Pad in Cleft Palate Repair.

OBJECTIVE: To review the available evidence on the use of the Buccal Fat Pad in primary and secondary Cleft Palate repair. METHODS: This is a narrative review. A computerized literature search was conducted for articles published till February 2022 using the Mesh phrases buccal fat pad AND cleft palate, Bichat's Fat pad AND cleft palate, buccal fat pad OR Bichats Fat pad AND cleft palate. RESULTS: A total of 35 articles were included in this review based on the set eligibility criteria. Most of the studies were retrospective case reviews (n = 16, 45.7%), and the aggregate number of patients from all included studies was 666. Reported uses of the buccal fat pad (BFP) in association with cleft palate repair include the closure of central cleft palate defect and nasal floor in primary cleft palate repair, oronasal fistula repair following primary repair of cleft palate, and closure of relieving incision defect in primary repair of cleft palate. Complications reported were 24 cases of Oronasal Fistula (ONF), 2 dehiscences, and 4 transient mucosal defects. CONCLUSION: The high success rate, vascularity, ease of tissue harvest, and low donor site morbidity all support its use as an adjunct flap in cleft palate repair, especially in the closure of wide palatal clefts, to prevent post-palatal repair fistula, wound contracture, and subsequently velopharyngeal insufficiency and possibly midface hypoplasia.

SPECC1L regulates palate development downstream of IRF6.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

OBJECTIVES: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. MATERIALS AND METHODS: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. RESULTS: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. CONCLUSION: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.

Facial Anthropometry Measurements Using Three-Dimensional Stereophotogrammetry Analysis Among Nigerians.

ABSTRACT: This study aimed to determine the normative facial anthropometry measurement among Nigerians using three-dimensional stereophotogrammetry analysis.This study was carried out in Lagos, Nigeria over a period of 3 years. The sample population was Nigerians of diverse ethnic groups, age 16 and above with no history of congenital or acquired craniofacial deformities.A total of 452 subjects participated in the study with 56.2% males and 43.8% females. Most of the participants were between the ages of 25 to 49 (54.4%), 40.7% were less than 25 years of age and only 4.4% were more than 50 years old. The mean body mass index (BMI) for males was 22.7 and 23.4 for females. Mean values of upper facial height, midfacial height, lower facial height, intercanthal distance, interpupillary distance, upper facial width, and lower facial width are 69.13 ±â€Š5.91, 49.89 ±â€Š3.56, 67.85 ±â€Š6.12, 35.19 ±â€Š3.20, 67.04 ±â€Š3.67, 139.43 ±â€Š7.11, and 124.29 ±â€Š9.72 mm, respectively. The upper facial height, commissure width, upper lip length, and lower jaw width were significantly affected by age, while the BMI of an individual was a determinant of the interpupillary distance, facial width, and lower jaw width.This study demonstrated that there was a statistically significant difference in the facial dimensions of males when compared to females across all ages among the study population. The authors also observed that age and BMI are significant predictors of variations in some of the measurements.

Comparing the Treatment Outcomes of Absorbable Sutures, Nonabsorbable Sutures, and Tissue Adhesives in Cleft Lip Repair: A Systematic Review.

OBJECTIVES: To examine the literature and synthesize the available reports for the best possible option between absorbable, nonabsorbable, and tissue adhesives in cleft lip skin closure. DESIGN: We conducted systematic searches for randomized controlled trials and controlled clinical trials in PubMed, Cochrane, Ovid Medline, and OpenGrey databases. Identified studies were retrieved and assessed for eligibility. All statistical analyses were done with Revman, version 5.4. INTERVENTIONS: The intervention considered in this systematic review were techniques of cleft lip repair using resorbable sutures, nonabsorbable sutures, medical adhesives, or any combination of these. OUTCOME MEASURES: The primary outcomes assessed in the trials had to include any combination of the following: wound healing cosmesis and wound healing complications. While secondary outcomes considered were quality of life, direct and indirect costs to patients and health services, and participant satisfaction. RESULTS: Only 6 studies met all inclusion criteria and were selected for qualitative analysis. A more favorable wound healing cosmesis was seen when nonabsorbable suture was used in cleft lip repair compared to absorbable sutures and tissue adhesives (CI, 0.65-4.35). This advantage was overshadowed by the significantly higher prevalence of postoperative complications when nonabsorbable sutures are used. CONCLUSION: Although the results point to more favorable cosmesis with nonabsorbable sutures and an overall more favorable outcome with either absorbable sutures or tissue adhesives, the 6 selected studies were assessed at an unclear risk of bias; therefore, the results of this study should be interpreted with caution and regarded as low-certainty evidence.

Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P).

OBJECTIVE: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset. METHODS: The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P. RESULTS: We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16. CONCLUSION: Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.

Damaging Mutations in AFDN Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate.

Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts.We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P case-parent African trios to identify pathogenic variants that contribute to the risk of clefting. We replicated this analysis using whole-exome sequence data from a Brazilian nsCL ± P cohort. Computational analyses were then used to predict the mechanism by which these variants could result in increased risks for nsCL ± P.We discovered damaging mutations within the AFDN gene, a cell adhesion molecule (CAMs) that was previously shown to contribute to cleft palate in mice. These mutations include p.Met1164Ile, p.Thr453Asn, p.Pro1638Ala, p.Arg669Gln, p.Ala1717Val, and p.Arg1596His. We also discovered a novel splicing p.Leu1588Leu mutation in this protein. Computational analysis suggests that these amino acid changes affect the interactions with other cleft-associated genes including nectins (PVRL1, PVRL2, PVRL3, and PVRL4) CDH1, CTNNA1, and CTNND1.This is the first report on the contribution of AFDN to the risk for nsCL ± P in humans. AFDN encodes AFADIN, an important CAM that forms calcium-independent complexes with nectins 1 and 4 (encoded by the genes PVRL1 and PVRL4). This discovery shows the power of NGS analysis of multiethnic cleft samples in combination with a computational approach in the understanding of the pathogenesis of nsCL ± P.

Assessment of the utility of a screening tool for COVID-19 diagnosis in an accident and emergency department in Lagos, Nigeria: A pilot study.

The use of reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard laboratory test for diagnosing SARS-CoV-2 infection. However, it has the disadvantage of a long turnaround time and cost. The Nigeria Centre for Disease Control (NCDC) formulated a case definition for COVID-19. We sought to determine the utility of a 14-item, point-weighted clinical screening questionnaire adapted from the NCDC case definition in identifying patients more likely to have the disease. This was to aid prompt clinical decision-making. Methods: We retrospectively reviewed the data of 113 non-surgical patients presenting to the Accident and Emergency Department (A and E) of Lagos University Teaching Hospital, Lagos, Nigeria. Patients were stratified based on screening scores into low (0-2), moderate (3-5) and high (6) pre-test categories. Patients with low and high scores ≥6 were admitted to the A and E and the COVID-19 holding ward, respectively, while the moderate group had chest computed tomography scans to aid further decision-making, pending the outcome of their RT-PCR results. The validity of the triage score as compared to the RT-PCR test result was calculated and the kappa score of agreement was utilised to evaluate the concordance between two triage scores. The optimum cut-off score was also obtained based on the maximal Younden's index. Results: The frequencies of low, moderate and high pre-test scores were 34 (30%), 43 (38.1%) and 36 (31.9%), respectively. Overall, 38.1% (43/113) were RT-PCR positive. RT-PCR was positive in 26.5% (9/34) with low screening scores, 55.8% (24/43) with moderate scores and 27.8% (10/36) with high scores. The sensitivity and specificity of a high score of 6 were 25% and 92.86%, while the lower score of 3 had sensitivity and specificity of 62.5% and 58.6%, respectively. Conclusion: The screening tool showed a high specificity in its initial design, which suggests that anyone with a low score using this tool has a high probability of testing negative. We recommend a cut-off score of 4 (score A) or 6 (score B) of the current screening tool be used to increase the chances of identifying persons with COVID-19 for RT-PCR testing.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

How Does Octyl-2-Cyanoacrylate Tissue Adhesive Compare With Prolene Sutures in Cleft Lip Repair?

PURPOSE: Comparative evidence of the usefulness of octyl-2-cyanoacrylate tissue adhesive in cleft lip epidermal skin closure especially in Africans is still lacking. This study aimed to compare the outcome of wound healing after the use of Dermabond tissue adhesive and 5/0 Prolene sutures in cleft lip repair. METHODS: This was a prospective randomized controlled clinical study. The sampled population was patients undergoing cleft lip repair at a tertiary health facility in Lagos, Nigeria. Study patients were randomly allocated to either group A (Dermabond) or group B (suture). The predictor variable was the type of material used in skin closure; the primary outcome variable was the esthetics of the resulting scar, and secondary outcome variables were wound healing complications. Assessment of the 3-month postoperative wound scar was performed using the cosmetic visual analog scale (CVAS) and the Hollander Wound Evaluation scale (HWES). Calculated sample size was 14 participants per group. Descriptive and comparative statistics were computed, and the P value was set at <0.05. RESULTS: Analysis of result included 38 participants. Median age was 4 months and 52.6% were women. Two cases (5.3%) of wound healing complications were recorded (1 in each group). Blinded evaluation of the 3-month postoperative photographs yielded a mean CVAS score of 86.0 (±11.2) and HWES score of 5.0 (±0.9) for group A and a mean CVAS score of 76.5 (±14.5) and HWES score of 4.5 (±1.1) for group B. There was no statistically significant difference between these 2 groups based on the CVAS (P = .052) and HWES (P = .152). CONCLUSIONS: The results of this study suggest Dermabond offers a comparable cosmetic outcome as 5/0 Prolene suture in epidermal closure of cleft lip. There was no statistically significant difference in wound complications and wound cosmetic scores between the 2 groups.

Does the Initial Width of Cleft Lip Play a Role in the Occurrence of Immediate Local Complications Following Primary Cleft Lip Repairs?

OBJECTIVE: Among the several factors implicated in the occurrence of local surgical site complications following cleft lip repair is the initial width of the cleft. The aim of the study was to examine the effect of cleft width in the occurrence of immediate local surgical site complications. MATERIAL AND METHODS: All consecutive subjects with diagnosis of unilateral or bilateral cleft lip with or without cleft palate who presented at the cleft clinic and satisfied the inclusion criteria were recruited in the study. The width of the cleft lip defect as adopted for the study was measured from the peak of the Cupid bow on the non-cleft side to a point where the white roll begins to thin out on the cleft side. Measurement was done using a Vernier Calliper. Surgery was performed under general anesthesia after which subjects were evaluated for the presence or absence of immediate local surgical site complications which included dehiscence, infection, and vermillion notching of the lip. RESULTS: A total of 70 subjects consisting of 36 (51.4%) males and 34 (48.6%) females were included in the study. Mean age (±SD) was 9.0 ±â€Š(19.4) months with age range of 3 months to 13 years. The prevalence of early surgical site complications was 24.3%. The width of cleft above a critical level (14 mm) statistically correlate significantly with the occurrence of early surgical site complications (P = 0.048). CONCLUSION: This study showed that the width of cleft lip of and above critical level of 14 mm may be associated with a clinically significant risk of immediate local surgical site complications.

Missense Variants Within GJB2 Gene Locus and the Risk of Hearing Defects in Nonsyndromic Cleft Lip and Palate.

AIM: The aim of the study was to investigate the role of variants in GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip/palate. METHOD: Saliva samples were obtained from cases (subjects with orofacial clefts) and control (subjects without orofacial clefts) who consented to the study. Deoxyribonucleic acid (DNA) was extracted using standardized protocol at Butali Lab (Iowa, IA). Primers for the coding region of GJB2 was designed using Primer 3 (http://bioinfo.ut.ee/primer3-0.4.0/) and optimized in the Butali lab using a gradient polymerase chain reaction to determine the annealing temperature for each primer set (forward and reverse). We measured the DNA concentration using Qubit and XY genotyping done for quality control. A concentration of 5 ng/µL of DNA was used for Sanger sequencing. RESULTS: A total of 150 subjects were sequenced (66 cases; 84 controls). Mutations in GJB2 gene were detected in 2 individuals with cleft palate. We found p.Arg165Trp variant in 1 case and p.Leu81Val variant in the second case. Although p.Arg165Trp was predicted to be either benign or tolerated by SIFT/POLYPHEN, the single nucleotide change from C>T, that is, CGG>TGG leads to a premature stop codon preventing the protein formation. The p.Leu81Val variant was predicted to be probably damaging/ deleterious. CONCLUSIONS: The present study implicates variants in the GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip and palate in the Nigerian population. Screening for variations in GJB2 gene is important for genetic counseling especially in high-risk families.

The Influence of Sex and Ancestry on Three-Dimensional Palate Shape.

ABSTRACT: Modern human palate shape has been reported to vary by sex and ancestry, but limitations in the methods used to quantify shape and in population coverage have led to inconsistent findings. In the present study, the authors aim to characterize the effects of sex and ancestry on normal-range three-dimensional palate shape through landmark-based morphometrics.Three-dimensional digital dental casts were obtained and landmarked from 794 adults of European (n = 429), African (n = 295), and East Asian (n = 70) ancestry. Principal component analysis was conducted to identify patterns of shape variation present in our cohort, and canonical variates analysis was performed to test for shape differences between sexes and ancestries.Principal component analysis showed that 3 principal components, explaining 76.52% of variance, linked higher palatal vault with either a relative reduction in anteroposterior or mediolateral dimensions. Canonical variates analysis showed that males had wider and shorter palates with more posteriorly located maximum vault depth than females. Individuals of African ancestry, having higher vaults with more posteriorly located maximal depths, also had wider and shorter palates, whereas individuals of European ancestry had narrower and longer palates with more anteriorly located maximum vault depths. Individuals of East Asian ancestry showed the shallowest vaults.It was found that both sex and ancestry influence palate shape, suggesting a possible genetic component underlying this variation. Additionally, our findings indicate that vault height tends to co-vary with anteroposterior or mediolateral dimensions. Further investigation of these morphological patterns may shed light on possible links to common congenital anomalies such as orofacial clefting.

Oral Habits in Children With Orofacial Clefts: A Comparative Study.

BACKGROUND AND AIM: Children with cleft lip and palate present with a wide range of dental and occlusal anomalies as a result of the cleft defect. These patients also present with oral habits which may affect their quality of life. The aim of this study was to compare the prevalence of oral habits in these children, with children without orofacial clefts. METHODOLOGY: This was a cross-sectional comparative study comparing children with repaired cleft lip and/or palate aged 3 to 12 years, with children without orofacial clefts. Ethical approval for the study was obtained from the institutional review boards of both centers. Data collection was via interviewer administered questionnaires given to the parents/guardians of the children in each group. Data analysis was carried out using SPSS version 23. The level of significance was set at P < .05. RESULTS: A total of 107 respondents participated in the study, comprising 53 children with repaired cleft lip and/or palate 54 children without orofacial clefts. The mean age for the children with Cleft lip and/or palate/ was 6.81 (standard deviation [SD] 1.898) years, while that for the control group was 7.78 (SD 1.68) years. Two oral habits recorded a significantly higher prevalence (P < .05) in the children with repaired clefts as compared to controls and these were lip sucking and bruxism. No significant difference in prevalence was recorded for all the other oral habits surveyed. CONCLUSION: A significantly higher prevalence (P < .05) was observed in lip sucking and bruxism among children with cleft lip and palate, as compared to the children without orofacial clefts.