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In 1888, hard-working twelve-year-old Jocey Royal, tormented because of a disfiguring harelip, takes her invalid grandmother to live on the Kansas farm that her drifter father has abandoned.

Cleft lip and palate (CLP) is one of the most common congenital anomalies, affecting ~1 in 700 births worldwide. Patients with CLP often experience functional impairments due to the cleft palate, particularly related to feeding and speech. Surgical interventions are essential for addressing these issues, yet no standardized surgical procedure exists. Velar adhesion (VA) is a technique used to reduce the cleft width prior to a palatoplasty, potentially improving surgical outcomes, but its effectiveness remains unclear. The impact of VA on cleft-width reduction and the incidence of otitis media with effusion (OME) were evaluated in patients with unilateral cleft lip and palate (UCLP). The cases of 45 patients with UCLP who underwent a palatoplasty at the University of Tokyo Hospital between January 2013 and December 2023 were analyzed retrospectively. We divided the patients into two groups: those who underwent VA during lip repair (VA group) and those who did not (non-VA group). The cleft width and alveolar cleft width were measured at birth, lip repair, and palatoplasty. The presence of OME was assessed the day before the palatoplasty. Pearson's chi-square test and the two-tailed t-test were applied. Significant cleft-width reduction was observed in the VA group compared to the non-VA group at the time of palatoplasty (4.58 mm vs. 6.55 mm, p < 0.01). The incidence of OME was significantly lower in the VA group (60.00%) versus the non-VA group (90.91%, p < 0.01). No significant between-group differences were identified for the alveolar cleft width or maxillary growth. VA significantly reduces the cleft width at the junction of the hard and soft palates, and it may decrease the incidence of otitis media with effusion in patients with UCLP. VA is a straightforward procedure with potential benefits for improving palatoplasty outcomes and mitigating complications such as OME.

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.

Objectives Clinicians agree that children with isolated cleft lip have fewer cleft-associated problems than children with cleft lip and palate. Unfortunately, for isolated cleft lip children, the risk of cleft-associated problems is unknown and maybe underestimated. Often, these children do not get the required follow-up by a multidisciplinary team and thereby not the known benefits in supporting their development. This study examines the incidence of cleft-related speech problems and ear problems in children with isolated cleft lip. Materials and methods A prospective study was performed on all children born with an isolated cleft lip and treated at the Wilhelmina Children’s Hospital in Utrecht between January 2007 and April 2014. Data were collected for sex, date of birth, genetics, cleft lip type, date of cleft lip repair, type of repair, speech/language problems, and ear problems. Results This study included 75 patients (59% male). The mean age of the children at the moment of speech examination was 32.5 months (SD 6.1). Eighteen of the 75 children (24%) needed speech and language therapy; however, only one child (1.3%) had a cleft-related speech problem. Sixteen of the 75 patients (21%) reported a history of one or more episodes of acute otitis media (AOM)/otitis media with effusion (OME) during the first 6 years. Conclusion/clinical relevance This is the first prospective study analyzing the incidence of cleft-related speech problems in children with an isolated cleft lip. These children do not have a higher risk of cleft-related speech problems or AOM/OME when compared to the general population. However, children with an isolated cleft do have a higher incidence of speech therapy.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

Elisabeth Mangold and colleagues report a genome-wide meta-analyses of non-syndromic cleft lip with or without cleft palate (NSCL/P). They report six new genetic loci associated with risk for NSCL/P. We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; P NSCLP = 6.51 × 10 −11 ; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84–3.16).

Objective: The aim of the study was to conduct a meta-analysis of research examining the early speech and language functioning of young children, birth to age 8;11 (years;months), with nonsyndromic cleft lip and/or palate (NSCL/P) compared to their peers without NSCL/P. Method: We conducted a random-effects metaregression using 241 effect sizes from 31 studies comparing 955 young children with NSCL/P to 938 typically developing peers on measures of speech and language functioning. Moderators were sample characteristics (i.e., age, cleft type, publication year, and study location) and measurement characteristics (i.e., speech sample material, language modality and domain, and assessment type). Results: Young children with NSCL/P scored significantly lower on measures of speech and language compared to children without NSCL/P. Children with NSCL/P had smaller consonant inventories (standardized mean difference effect size [ES[subscript g]] = -1.24), less accurate articulation (ES[subscript g] = -1.13), and more speech errors (ES[subscript g] = 0.93) than their peers. Additionally, children with NSCL/P had poorer expressive (ES[subscript g] = 0.57) and receptive (ES[subscript g] = -0.59) language skills than their peers. Age and assessment type moderated effect sizes for expressive language. As children with NSCL/P aged, their expressive language performance became more similar to their peers. Expressive language effect sizes from parent reports and observational language measures (estimated effect size = -0.74) were significantly lower than those from standardized norm-referenced tests (estimated effect size = -0.45). Conclusions: These findings suggest that young children with NSCL/P experience delays relative to their peers across multiple speech and language constructs. Differences between children with NSCL/P and their typically developing peers appear to decrease with age.

Orofacial cleft disorders, including cleft lip and/or palate (CL/P), are one of the most frequently-occurring congenital disorders worldwide. The health issues of patients with CL/P encompass far more than just their anatomic anomaly, as patients with CL/P are prone to having a high incidence of infectious diseases. While it has been previously established that the oral microbiome of patients with CL/P differs from that of unaffected patients, the exact nature of this variance, including the relevant bacterial species, has not been fully elucidated; likewise, examination of anatomic locations besides the cleft site has been neglected. Here, we intended to provide a comprehensive review to highlight the significant microbiota differences between CL/P patients and healthy subjects in various anatomic locations, including the teeth inside and adjacent to the cleft, oral cavity, nasal cavity, pharynx, and ear, as well as bodily fluids, secretions, and excretions. A number of bacterial and fungal species that have been proven to be pathogenic were found to be prevalently and/or specifically detected in CL/P patients, which can benefit the development of CL/P-specific microbiota management strategies.

Key Points Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP affects approximately 1 in 700 live births, with wide variability across geographic origin, racial and ethnic groups, as well as environmental exposures and socioeconomic status. CLP can occur in syndromic or non-syndromic forms. This Review focuses on the latter. Although twin studies and familial clustering studies have provided compelling evidence for a genetic component to non-syndromic CLP, few pedigrees show clear-cut Mendelian inheritance and many cases appear to be sporadic. Accurate phenotyping is crucial to understanding both the epidemiology and aetiology of any congenital malformation because the power to detect effects is weakened when heterogeneous groups are treated as a single entity. To date, genetic approaches to non-syndromic CLP have included: linkage analysis using large, multiplex families or smaller but inbred families, or analysis of affected relative pairs; association studies using case–parent trios or case–control samples; identification of chromosomal anomalies or micro-deletions in cases; and direct sequencing of affected individuals. Genome-wide association studies have provided recent major advances in our understanding of genes and pathways that have a role in the aetiology of CLP. There is remarkable heterogeneity by ancestry in the relative contributions by genes found with common variants contributing to CLP. There is evidence that environmental factors have a role in CLP risk and interactions of the environment with certain genetic variants have been identified. The next critical phase of statistical analyses will be to examine the heterogeneity underlying the aetiology of oral clefts and to investigate the gene–gene and gene–environment interactions that control risk. Integration of genetic and environmental risk using epigenetics, systems biology, gene expression and epidemiology will be required to generate a synthesis that will both better characterize aetiologies and eventually lead to improvements in prevention and clinical care. Clefts of the lip and/or palate are common and have a complex genetic and environmental basis. Recent work on these birth defects illustrates the value of combining genome-wide association studies, animal models and improved clinical phenotyping. Future work may also address gene–environment interactions. Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.

Cleft of the lip and palate is the most common craniofacial birth defect with a worldwide incidence of one in 700 live births. Early surgical repairs are aimed at improving appearance, speech, hearing, psychosocial development and avoiding impediments to social integration. Many interventions including the Smile Train partner model have been introduced to identify and perform prompt surgical procedures for the affected babies. However, little is known about the trends of the incidence and surgical procedures performed at our hospital. Nothing is also known about the relationship between the clinical characteristics of the patients and the timing of primary repairs. To determine the trends in cleft surgeries, patterns of cleft surgeries and identify factors related to late primary repair at the University College Hospital, UCH, Ibadan, Nigeria. A retrospective cohort study and trends analysis of babies managed for cleft lip and palate from January 2007 to January 2019 at the UCH, Ibadan was conducted. The demographic and clinical characteristics were extracted from the Smile Train enabled cleft database of the hospital. The annual trends in rate of cleft surgeries (number of cleft surgeries per 100,000 live births) was represented graphically. Chi square test, Student's t-test and Mann Whitney U were utilised to assess the association between categorical and continuous variables and delay in cleft surgery (≥12 months for lip repair, ≥18months for palatal repair). Kaplan-Meier graphs with log-rank test was used to examine the association between sociodemographic variables and the outcome (late surgery). Univariable and multivariable Cox proportional hazard regression was conducted to obtain the hazard or predictors of delayed cleft lip surgery. Stata version 17 (Statacorp, USA) statistical software was utilised for analysis. There were 314 cleft surgeries performed over the thirteen-year period of study. The male to female ratio was 1.2:1. The mean age of the patients was 58.08 ± 99.65 months. The median age and weight of the patients were 11 (IQR:5-65) months and 8 (IQR: 5.5-16) kg respectively. Over half (n = 184, 58.6%) of the cleft surgeries were for primary repairs of the lip and a third (n = 94, 29.9%) were surgeries for primary repairs of the palate. Millard's rotation advancement flap was the commonest lip repair technique with Fishers repair introduced within two years into the end of the study. Bardachs two flap palatoplasty has replaced Von Langenbeck palatoplasty as the commonest method of palatal repair. The prevalence of late primary cleft lip repair was about a third of the patients having primary cleft lip surgery while the prevalence of late palatal repair was more than two thirds of those who received primary palatoplasty. Compared with children who had bilateral cleft lip, children with unilateral cleft lip had a significantly increased risk of late primary repair (Adj HR: 22.4, 955 CI: 2.59-193.70, P-value = 0.005). There has been a change from Von Langenbeck palatoplasty to Bardachs two-flap palatoplasty. Intra-velar veloplasty and Fisher's method of lip repair were introduced in later years. There was a higher risk of late primary repair in children with unilateral cleft lip.