Genome-wide and Interaction Linkage Scan for Nonsyndromic Cleft Lip with or without Cleft Palate in Two Multiplex Families in Shenyang,China

Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P.Blood of every member was drawn for DNA extraction and analysis.Genotypes were available for 382 autosomal short tandem repeat （STR） markers from the ABI Prism Linkage Mapping Set version 2.5.Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores,multipoint heterogeneity parametric LOD scores （HLODs）,and multipoint nonparametric linkage score （NPL）.Results The initial scan suggested linkage on Chromosomes 1,2,and 15.In subsequent fine mapping,1q32-q42 showed a maximum multipoint LOD score of 1.9（empirical P=0.013） and an NPL score of 2.35 （empirical P=0.053）.For 2p24-p25,the multipoint NPL increased to 2.94 （empirical P=0.007）.2-locus interaction analysis obtained a maximum NPL score of 3.73 （P=0.00078） and a maximum LOD score of 3 for Chromosome 1 （at 221 cM） and Chromosome 2 （at 29 cM）.Conclusion Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42,suggesting a susceptibility locus in this region.Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25.The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25,and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.

Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.

Assessment of Two Years of Free Surgical Treatment of Cleft Lip, Palate and Alveolar (CLPA) in the Maxillofacial Surgery and Stomatology Department of the Hospital University of Treichville-Abidjan

Introduction: Cleft lip, palate and alveolar (CLPA) are congenital malformations of the face due to a defect in the fusion of embryonic buds during the first weeks of embryogenesis. These malformations affect the upper lip, the alveolar bone and the palate. The incidence in Africa ranges from 1/2000 to 1/500 births. Their multidisciplinary management is long and costly. Thus, the help provided by humanitarian organisations during free care campaigns is welcome. Materials and Methods: This is a retrospective descriptive study conducted from August 2014 to July 2016 in the Maxillofacial Surgery and Stomatology Department of the Treichville University Hospital in Abidjan, Côte d’Ivoire. The objective was to describe the epidemiological, clinical and therapeutic aspects of CLPA during a humanitarian campaign for free care. Results: 51 cases of CLPA were operated on. Males were involved in 54.9% of the cases, i.e. a sex ratio of 1.2. The average age of the patients at the time of the operation was 3.44 years with extremes of 3 months and 52 years. Patients with low socioeconomic status represented 84.3% of the cases. Cleft lips (31.4%) and cleft palates (33.33%) predominated. For cleft lips, unilateral forms were the most frequent (73.5%) and the left side was most often affected (59.2%). The most common surgical techniques used were MILLARD cheiloplasty for cleft lips (79.36%) and Dorrance pushback for cleft palates (78.05%). The postoperative course was simple in the majority of cases (80.47%). Patients and/or parents were satisfied with the postoperative results in over 90% of cases. Discussion: Cleft lip and palate are common. Their management by humanitarian missions through mass campaigns allows us to receive a large number of patients affected by this pathology who are treated with a high satisfaction rate. Conclusion: The characteristics of cleft lip and palate in this study are in many respects identical to those described in the literature, but with some differences specific to Africa, notably the absence of antenatal diagnosis and the advanced age at the time of treatment.

A Case-control Study of Environmental Risk Factors for Nonsyndromic Cleft of the Lip and/or Palate in Xuzhou,China

In this study, we sought to determine the association between environmental factors and nonsyndromic cleft of the lip and/or palate （NSCLP） to understand the etiology of the disease. A total of 200 NSCLP cases and 327 controls were recruited at the Maternal and Child Health Hospital of Xuzhou City. We conducted face-to-face interviews with the mothers of both cases and controls. The factors increasing the risk of NSCLP were a positive family history [odds ratio （OR）=56.74], pesticide exposure （OR=8.90）, and indoor decoration pollution （OR= 4.32）. On the other hand, the factors decreasing the risk of NSCLP were a high education level （OR=0.22） and supplementation of folic acid （OR=0.23） and multivitamins （OR=0.16）. Positive family history, pesticide exposure, and indoor decoration pollution are associated with the risk of NSCLP. In contrast, high education level and folic acid and multivitamin supplementation are protective factors against NSCLP.

Rhinoplasty in Cleft Lip and Palate

Various surgical techniques and approaches have been described to repair cleft nose deformities. It is necessary to consider that since it is a congenital deformity, surgical management must consider the patient’s growth process, as well as the healing itself from the surgery. The present study aims to evaluate an alternative solution to secondary rhinology, aesthetic, and functional alterations to unilateral or bilateral cleft lift palate to minimize deformities and ensure good results. 11 patients were studied between 1995 to 2002, ten male and one female. In 8 cases, the patients had a history of cleft lip and palate on the left side, 2 patients with cleft lift palate on the right, and 1 patient with bilateral cleft lip and palate. 100% of the patients increased their naso-labial angle. This improved their appearance and structure, starting from a preoperative arithmetic mean of 39 degrees to a postoperative arithmetic mean of 96 degrees. Such intervention increased the naso-labial angle by 57 degrees. At the base of the nose, it was possible to improve the inclination of the alar line (line B) in 10 of the cases with a variation of 2 to 3 mm in relation to the perpendicular line A and only one case remained with the same inclination.

Accurate diagnosis of prenatal cleft lip/palate by understanding the embryology

Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.

BHMT Gene Polymorphisms as Risk Factors for Cleft Lip and Cleft Palate in a Chinese Population

Objective Convincing evidence suggests a link between increased risk of nonsyndromic cleft lip with or without cleft palate （NSCL/P） and low intake of folic acid by the mother during pregnancy. The present study was designed to explore if genetic variation in the betaine‐homocysteine methyltransferase （BHMT） gene contributes to NSCL/P. Methods DNA was obtained from 166 individuals with NSCL/P and 285 healthy subjects. Three known single nucleotide polymorphisms （SNPs） present in the BHMT gene （rs651852, rs3797546, and rs3733890） were investigated by real‐time PCR‐based TaqMan genotyping. Results Neither allelic nor genotypic association was found between NSCL/P and SNPs rs651852 and rs3733890. SNP rs3797546 did not show allelic association with NSCL/P; however, a higher proportion of NSCL/P patients carry the CC genotype compared with the TT＋CT genotype （P=0.020, OR=2.10, 95% CI=1.11‐3.95）. Conclusion Our study suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner.

Lateral Crus Graft with Autologous Rib Cartilage for Cleft Lip Nostril Asymmetry: A Report of 35 Cases

Summary： A surgical technique of lateral crus strut graft to correct the deformity of nostril contour and improve asymmetric nostril shape by autologous rib cartilage was reported. Thirty-five patients （20 males and 15 females）, with a mean age of 19 years （range of 16-26 years） were included in this study. All of the patients suffered moderate to severe unilateral cleft lip nostril deformity and underwent surgical technique of lateral crus strut graft by autologous rib cartilage to correct the asymmetric nostril contour from 2010 to 2012. The views of the nostril contour on both sides were reviewed and some parameters were measured at different time points （preoperatively, and 3 months and one year postoperatively） including the long axis and short axis of the nostrils. The differences in nostrils including long axis, short axis, elliptical area and eccentricity on the both sides were compared at different time points. The differences in the long axis and eccentricity of the nostrils on the two sides were decreased significantly between the preoperative view and postoperative view （P〈0.05）. The surgical technique of lateral crus graft with autologous rib cartilage is effective to correct the abnormal nostril contour and improve the asymmetry for unilateral cleft clip patients.

Comparison of Congenital Tooth Deficiencies Seen in Permanent Teeth in Individuals with Unilateral Cleft Lip and Palate to Those without Cleft Lip and Palate

Objective: To compare the congenital tooth deficiencies seen in permanent dentition in individuals with unilateral cleft lip and palate (UCLP) to non-cleft individuals with Angle Class I malocclusion. Method: The study was performed on orthopantomograph films of 50 individuals with UCLP aged between 12 - 16 years and 50 individuals with Angle Class I malocclusion individuals aged between 13 - 15 years. Individuals with UCLP;32 clefts were on the left side and 18 clefts were on the right side. Permanent third molar teeth deficiency was excluded from the study. Results: In 50 individuals with UCLP;35 (70%) upper lateral incisors were congenitally deficient in the cleft area, while 15 (30%) missing lateral teeth were found in the non-cleft side. In control group, 12 (24%) of 50 patients had congenital lateral incisor deficiency. Congenital deficiency of upper lateral incisor in UCLP;the cleft area was higher than the non-cleft side (p < 0.01). The difference was statistically important when compared with the control group (p < 0.001). In 50 individuals with UCLP;while 27 (54%) of second premolar teeth were congenitally deficient in cleft side, 23 (46%) were missing in non-cleft side. In control group, 18 (36%) congenital second premolar deficiency was detected. However, second premolar congenital deficiency was higher in UCLP group when compared to control group (p < 0.01). Conclusion: The deficiency of the lateral incisors in the cleft side is more often congenitally deficient than upper second premolar teeth and this should be considered in the treatment planning from an early age.

Cleft Lip Surgical Intervention in Resource Constraint Settings: A Case Report

Cleft lip and palate is a very common condition which is globally undertreated. This case report shows how cleft lip surgery can transform patient’s lives, self-perception, and their self-esteem through a visionary and adaptive leadership of a few social workers and medical doctors in resource constrained settings. The case report also shows that when treated, the benefits to the patient and their family are lifelong and disproportionately large compared to the degree of effort and cost of doing the reconstruction;and puts forth the case for educating physicians to maximize their societal benefit through work in resource-constrained settings.

Upper Airway Changes after Maxillary Distraction Osteogenesis in Cleft Lip and Palate Patients

Purpose: To measure the upper airway changes associated with maxillary distraction osteogenesis in cleft lip and palate patients in the immediate post operative period and 12 months later. Materials and Methods: Seven patients with repaired cleft lip and palate (CLP) presented with severe maxillary hypoplasia. They were examined initially at T1 predistraction phase. Records taken included radiographs (orthopantograms OPG, lateral cephalometric, posteroanterior). Cephalometric analysis was done to evaluate the upper airway. Mean age is 17 years and the reverse overjet > 6 mm. They underwent maxillary Le Fort I distraction using external rigid distracters (RED). Cephalometric analysis to evaluate the upper airway was repeated at the end of the consolidation phase T2 and twelve months after distractor removal T3. Results: The range of maxillary advancement was between 8 - 15 mm (mean 9 mm). The anteroposterior distance of the superior velopharynx (PPS) and middle velopharynx (SPPS) increased at T2. A small amount of reduction in these values was recorded at T3. The inferior velopharynx (MPS) and the oropharynx (IPS, EPS) showed minimum increase in anteroposterior distance in only two patients at T2 and no change at T3. Conclusion: All seven patients showed clinical improvement in the upper airway and an increase in the upper airway values on lateral cephalometric radiographs.

Expectations of Caregivers of Patients with Cleft Lip and Palate Attending the Cleft Clinic of KATH for the First Time

Background: Cleft lip and palate (CLP) is one of the most prevalent congenital malformations affecting the face worldwide, with high prevalence in Asians, Americans, and Caucasians and low in Africans. Orofacial Clefts (OFCs) are among the causes of perinatal death in Ghana. The children often experience difficulties in swallowing, feeding, and speaking. These children often face problems in cognition, education, and communication. Caregivers’ ignorance of treatment, poverty, and noncompliance with follow-up schedules are obstacles to optimal cleft care. Most studies focus on the incidence of cleft, but not much is known about caregivers’ expectations. Methodology: An exploratory qualitative study design was used for this research between October and November 2020. The study site was the Komfo Anokye Teaching Hospital, (KATH), Kumasi, Ghana. The respondents were recruited from the oral health clinic. Included in the study were all CLP caregivers attending the cleft clinic for the first time. Purposive sampling was used to select fifteen caregivers who met the inclusion criteria. Face-to-face interviews with a semi-structured interview guide were used to collect data. The data were analyzed using NVivo software. Three major themes and six sub-themes emerged from the data analysis using thematic analysis. Ethical clearance was obtained for data collection. Results: Most caregivers were expecting their babies to be operated on, and they were certain that the cleft would be repaired at the end of the treatment, but they were unfamiliar with the process and cost of treatment. Less than half of the caregivers reported that they were oblivious to what to expect the first time visiting but had hopes that the healthcare professionals would be able to close the cleft for their babies. Conclusion: The majority of the caregivers expressed fear and disappointment at the diagnosis of their child. Some caregivers were very scared to the level where they had to hide the babies from the public. Others reported being already in financial difficulties, so their children’s conditions would compound them.

TYMS gene 5'-and 3'-untranslated region polymorphisms and risk of non-syndromic cleft lip and palate in an Indian population

Dear Editor： Increased homocysteine levels due to vitamin B6 or B12 deficiency or genetic defects in folate pathway genes are associated with an increased incidence of non-syndromic cleft lip with or without cleft palate （NSCLP）tlj. Thymidylate synthase （TS） is a folate-dependent enzyme that catalyzes methylation of 2＇-deoxyuridine-5＇-monophosphate （dUMP） to 2＇-deox- ythymidine-5＇-monophosphate （dTMP）, a rate-limiting step in DNA synthesis,

Adult Cleft Lip Repair under Local Anaesthesia: The Ghana Experience

Background: Unlike developed countries where adult primary cleft lip and palate cases are barely nonexistent, developing countries still have a backlog of adults with unrepaired cleft lip and palate. Method: A retrospective review of adult/adolescent cleft lip repair under local anesthesia was performed between 2012 and 2015. Results: Fifty six (56) adolescent and adults were seen comprising 35 females and 21 males. Forty two patients presented with unrepaired unilateral cleft lip of which only 6 were complete;4 were unrepaired bilateral cleft lip and 10 were revisions. The lowest age was 13 years (two patients) and the highest age was 66 years (one patient). The mean weight was 54 kg. The mean anaesthetic time including waiting time was 12.94 minutes and mean operation time was 56.52 minutes. Majority of the patients were discharged same day except for five who needed to stay overnight because of distance from their home. There were no reported early postoperative complications and wound healing was uneventful for all the patients. Conclusion: Cleft lip repair in adults under local anesthesia is safe, effective and less expensive. A modification in technique with minimal dissection and efficiency is essential in such cases.

Genome-Wide Screening of Aberrant Methylation Loci for Nonsyndromic Cleft Lip

Background： The pathogenicity of cleft lip （CL） is pretty complicated since it is influenced by the interaction of environment and genetic factors. The purpose of this study was to conduct a genome-wide screening of aberrant methylation loci in partial lesion tissues of patients with nonsyndromic CL （NSCL） and preliminarily validate candidate dysmethylated genes associated with NSCL.Methods： Fifteen healthy and sixteen NSCL fetal lip tissue samples were collected. The Infinium HumanMethylation450 BeadChip was used to screen aberrant methylation loci in three NSCL and three healthy lip tissues. The differential methylation sites and functions of the annotated genes between NSCL and healthy lip tissues were analyzed using minfi package of R software, cluster analysis, Gene Ontology （GO） annotation, and metabolic pathway annotation. Gene expression was assessed in nine differentially methylated genes by real-time polymerase chain reaction （PCR）. The transcriptions mRNA levels of three out of nine candidate genes were downregulated remarkably in NSCL lip tissues, and these three genes＇ abnormal methylation loci were validated by pyrosequencing in 16 NSCL cases and 15 healthy cases.Results： In total, 4879 sites in the genes of NSCL odinopoeia fetuses showed aberrant methylation when compared with normal lip tissue genome. Among these, 3661 sites were hypermethylated and 1218 sites were hypomethylated as compared to methylation levels in healthy specimens. These aberrant methylation sites involved 2849 genes and were widely distributed among the chromosomes. Most differentially methylated sites were located in cytosine-phosphoric acid-guanine islands. Based on GO analysis, aberrantly methylated genes were involved in 11 cellular components, 13 molecular functions, and a variety of biological processes. Notably, the transcription of DAB1, REELIN, and FYN was significantly downregulated in lesion tissues of NSCL fetus （P 〈 0.05）. Pyrosequencing results validated that there were two loci in DABI with high methylation status in patient tissues （P 〈 0.05）. Conclusions： We detected numerous aberrantly methylated loci in lesion tissues of NSCL fetus. Aberrant gene expression in the REELIN signaling pathway might be related with NSCL. Decreased transcription of DAB1, a member of REELIN signal pathway, resulted from its abnormal high methylation, which might be one of the factors underlying the occurrence of NSCL.

Review on the clinical application of autologous fattransplantation in secondary lip malformation after cleft lip surgery

Congenital cleft lip is a common congenital defect.At present,surgical treatment is the only effective treatment for congenital cleft lip.Currently,there are many surgical methods for cleft lip.Many scholars continue to the improvement of surgical methods,and the immediate effect after surgery is significantly improved.However,despite the continuous improvement of surgical methods,lip and nose deformities are inevitably left after cleft lip.Because the lip occupies an important aesthetic position in the face,the restoration of secondary lip deformity after cleft lip surgery has important clinical significance.There are individual differences in secondary lip deformities in patients with cleft lip,and there are various methods of rehabilitation.There is no uniform treatment standard.This article mainly focuses on the current treatment progress of secondary lip deformities after cleft lip,especially autologous fat transplantation in secondary lip deformity after cleft lip is reviewed as follows.

Three-dimensional finite element analysls for external midface distraction after different osteotomy in patients with cleft lip and palate

Objective To study three - dimensional finite element analysis for external midface distraction after different osteotomy in patients with cleft lip and palate ( Clp) . Methods Three - dimensional Fem models of Le Fort Ⅰ,Ⅱand Ⅲ,osteotomy in Clp patients were estabolished. External midface distraction were simulated. An anteriorly and inferiorly directed 900 g force was

Correction of secondary deformity of unilateral cleft lip with refined anatomic repair in orbicularis oris muscle

Objective To investigate the functional repair of secondary deformity of unilateral cleft lip. Methods The nasal branch,nasolabial branch,and labial branch of orbicularis oris muscle were dissected and repositioned precisely to correct the secondary deformity of unilateral cleft lip. Results 96 parients were treated

Repair of the Median Microform Cleft Lip Using Z-Plasty

A median cleft lip is a rare central midline deficiency of the upper lip. Multiple surgical techniques are described in the literature to address this defect, though there is little consensus on the preferred surgical technique. We describe an intra-oral approach for repair of the median upper lip cleft using mucosal Z-plasty. This technique provides excellent access to the attenuated orbicularis oris muscle and the frenulum fibrosed to the labial margin. The tethered lip can be mobilized and the notch converted with appropriate mucosal length, lip height, and vermillion fullness. The contour of the free labial border immediately improves, all while avoiding a cutaneous scar. The midline cleft lip notch can be effectively treated by adhering to 3 major principles: 1) excision of the tight, constrictive labial band;2) achieving midline orbicularis oris muscle approximation;and 3) establishing mucosal lengthening using a Z-plasty.

Effect of Cleft Lip and Palate Repair on Craniofacial Morphology in Patients with Unilateral Complete Cleft Lip and Palate.

目的 :通过对替牙期正常儿童及单侧完全唇腭裂 (UCLP)患者X线头影测量侧位片进行比较研究 ,了解唇腭裂及其手术对颌骨发育的影响 ,探索继发畸形的发病机制。方法 :将替牙期的正常儿童及UCLP患者分为四组 :①正常对照组 (Normal) ,本组包括 48名替牙期正常湖北地区儿童 ;②未手术组 (NO) ,本组 10名UCLP患者未经任何手术治疗 ;③唇裂修复组 (OL) ,34名UCLP患者已行唇裂修复 ,腭裂暂未手术 ;④唇腭裂修复组 (OLP) ,16名UCLP患者已行唇、腭裂修复。各受试对象拍摄X线头影测量侧位片 ,测量描述颌骨的形态特征及生长方向 ,对各组之间测量结果进行统计学分析。结果 :未行手术治疗的U CLP患者颌骨形态除腭部先天性发育不足外 ,颌骨侧位头影测量与正常无显著性差异 ;OL和OLP组较正常存在严重的颌骨畸形 ,主要表现为上颌后缩、位置后移 ,同时下颌骨向后下旋转移位 ;OL和OLP组上颌后缩的程度无显著性差异。结论 :UCLP患者颌骨具有趋于发育正常的生长能力 ;手术是导致颌骨继发畸形的主要因素 ;对于单侧完全唇腭裂患者 。