Protective effect of Sasa veitchii extract against all-trans-retinoic acid-induced inhibition of proliferation of cultured human palate cells.

Cleft palate is the most common facial birth defect worldwide. It is caused by environmental factors or genetic mutations. Environmental factors such as pharmaceutical exposure in women are known to induce cleft palate. The aim of the present study was to investigate the protective effect of Sasa veitchii extract against medicine-induced inhibition of proliferation of human embryonic palatal mesenchymal cells. We demonstrated that all-trans-retinoic acid inhibited human embryonic palatal mesenchymal cell proliferation in a dose-dependent manner, whereas dexamethasone treatment had no effect on cell proliferation. Cotreatment with Sasa veitchii extract repressed all-trans-retinoic acid-induced toxicity in human embryonic palatal mesenchymal cells. We found that cotreatment with Sasa veitchii extract protected all-trans-retinoic acid-induced cyclin D1 downregulation in human embryonic palatal mesenchymal cells. Furthermore, Sasa veitchii extract suppressed all-trans-retinoic acid-induced miR-4680-3p expression. Additionally, the expression levels of the genes that function downstream of the target genes ( ERBB2 and JADE1 ) of miR-4680-3p in signaling pathways were enhanced by cotreatment with Sasa veitchii extract and all-trans-retinoic acid compared to all-trans-retinoic acid treatment. These results suggest that Sasa veitchii extract suppresses all-trans-retinoic acid-induced inhibition of cell proliferation via modulation of miR-4680-3p expression.

A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.

BACKGROUND: Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. METHOD: The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. DISCUSSION: We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. TRIAL REGISTRATION: ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family.

BACKGROUND Non-syndromic cleft lip with cleft palate (NSCLP) is one of the most common congenital birth defects worldwide; it causes lifelong problems and imposes burdens on patients and their families. This study aimed to describe the genomic analysis and identification of de novo regulated endocrine-specific protein 18 (RESP18) rs2385404 and rs2385405 gene polymorphisms associated with NSCLP in a southern Chinese family and to improve prevention, treatment, and prognosis of NSCLP. MATERIAL AND METHODS We performed a genome-wide association study (GWAS) to investigate the association of NSCLP phenotype with gene mutation. We investigated a 5-persons NSCLP family to screen the genetic variation of Han nationality in southern Chinese. Whole-genome sequencing (WGS) was used to detect all candidate genetic variants, and whole-exome sequencing (WES) was implemented to further verify mutations. The Clinical Variation Data Base (ClinVar) was employed for screening gene mutations. Finally, Sanger sequencing was applied to verify gene variations. RESULTS The combined analysis of WGS, WES, and ClinVar showed that a total of 9 variation positions overlapped among the 3 study cohorts. Sanger sequencing verified Glu amino acid variation in 2 mutation sites (rs2385404, rs2385405) from the RESP18 gene, which caused abnormal RESP18 function and was associated with hereditary NSCLP. CONCLUSIONS The combined genomic results showed that 2 mutations (rs2385404 and rs2385405) of the RESP18 gene were related to NSCLP in the family. The RESP18 gene may play an important role in the etiology and pathogenesis of cleft lip and palate.

Oronasal Fistula Closure and Defect Reconstruction: Two Case Reports Using Periodontal Plastic Surgery Principles.

OBJECTIVES: Oronasal fistulas are common sequelae following cleft lip and palate surgery and can significantly impact a patient's quality of life. They result from various factors, including surgical techniques, tissue management, and patient-specific factors. This case report explores the modern approach to oronasal fistula closure using periodontal plastic surgery principles. MATERIALS AND METHODS: The report presents two cases of patients with oronasal fistulas due to previous maxillofacial surgical intervention. These patients underwent microsurgical procedures that involved partial flap thickness preparation of the fistula areas, the use of connective tissue grafts from the palate, and meticulous suturing techniques to ensure graft integrity. The procedures were performed in stages, and postoperative care was provided. RESULTS: Both cases demonstrated successful fistula closure and graft survival. The patients reported improvements in breathing, speech, aesthetics, and quality of life. The second case also included guided bone regeneration and implant placement. CONCLUSIONS: Oronasal fistulas resulting from maxillofacial surgery can be effectively treated using periodontal plastic surgery techniques, significantly improving patients' quality of life and aesthetic outcomes. This approach represents a valuable addition to the existing repertoire of oronasal fistula closure methods.

The Cleft Collective: protocol for a longitudinal prospective cohort study.

INTRODUCTION: Cleft lip and/or palate (CL/P) affects 1 in 700 live births globally. Children born with CL/P and their families face various challenges throughout the child's development. Extant research is often limited by small numbers and single-centre data. The Cleft Collective, a national cohort study in the UK, aims to build a resource, available to collaborators across the globe, to understand causes, best treatments and long-term outcomes for those born with CL/P, ultimately seeking to enhance their quality of life through improved understanding and care. METHODS AND ANALYSIS: A longitudinal prospective cohort study of children born with CL/P and their families. Recruitment occurs across the UK and started in November 2013. Recruitment will continue until September 2027 with an estimated final sample of 4822 children born with CL/P (1157 cleft lip including/excluding the alveolus; 2112 cleft palate only; 1042 unilateral cleft lip and palate and 511 bilateral cleft lip and palate). Biological samples are collected from all recruited members of the family. Parental and child questionnaires are collected at key time points throughout the child's development. Surgical data are collected at the time of surgical repair of the child's cleft. Consent is obtained to link to external data sources. Nested substudies can be hosted within the cohort. Regular engagement with participants takes place through birthday cards for the children, social media posts and newsletters. Patient and Public Involvement is conducted through the Cleft Lip And Palate Association and Cleft Collective Patient Consultation Group who provide insightful and essential guidance to the Cleft Collective throughout planning and conducting research. ETHICS AND DISSEMINATION: The Cleft Collective was ethically approved by the National Research Ethics Service committee South West-Central Bristol (REC13/SW/0064). Parental informed consent is required for participation. Findings from the Cleft Collective are disseminated through peer-reviewed publications, conference presentations, newsletters and social media.

Single vs. Double-Opposing Z-Plasty: Evaluating Their Impact on Palatoplasty Postoperative Outcomes.

BACKGROUND: The double-opposing Z-plasty is a fundamental approach for cleft palate repair. Recently, some surgeons have begun implementing a single Z-Plasty, igniting discussions on the most effective technique for enhancing postoperative outcomes. Consequently, this study sought to evaluate the outcomes of employing single and double Z-plasties within the modified Sommerlad-Furlow technique. METHODS: 116 cleft palate patients undergoing primary surgical repair were divided into two groups: those treated with the Sommerlad-Furlow method using a double-opposing Z-plasty (S.F.2.Z.P. group, n = 58) and those receiving a single nasal Z-plasty (S.F.1.Z.P. group, n = 58). Data on cleft type and width, soft palate length, palatal fistula, and velopharyngeal function were collected. Mann-Whitney test compared the mean values between groups. RESULTS: The S.F.2ZP group demonstrated a statistically significant increase in soft palate length compared to those in the S.F.1ZP group (p = 0.008). However, the S.F.1ZP group demonstrated adequate soft palate length (7.9 ± 2.8 mm) compared to the S.F.2ZP group (9.3 ± 2.8 mm). The velopharyngeal function was good in both groups, with no significant differences (P = 0.52). While the proper velopharyngeal closure was 81% in the S.F.1ZP group and 87.9% in the S.F.2ZP group, velopharyngeal insufficiency was 10.3% and 5.2%, respectively. The rates of persistent palatal fistula were 5.2% in the S.F.1ZP group and 3.4% in the S.F.2ZP group, with no significant differences found between both groups (P = 0.64). CONCLUSIONS: There were no significant differences in crucial outcomes such as velopharyngeal function and the incidence of persistent palatal fistulas, indicating the effectiveness of both techniques. While the double-opposing Z-plasty demonstrated a statistically significant increase in soft palate length, the a nasal Z-plasty demonstrated adequate soft palate length which sufficiently enables effective velopharyngeal closure. These outcomes suggest that a single Z-plasty is both effective and easy to perform, making it a valuable surgical approach for achieving the desired outcomes.. CLINICAL RELEVANCE: The current study suggests that although the soft palate may not be as elongated with nasal Z-plasty alone compared to the double Z-plasty, it sufficiently enables effective velopharyngeal closure.

Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series.

BACKGROUND: Surgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population. CASE PRESENTATION: A total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 µg/kg was administered within 10 minutes, and a maintenance dose of 1.5 µg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients. CONCLUSION: Dexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.

A retrospective analysis of factors affecting speech production in school-aged children with cleft palate (+- cleft lip).

OBJECTIVE: The present investigation examined how factors such as cleft type, age of primary palatal surgery, diagnosed syndromes, hearing problems, and malocclusions could predict persistent speech difficulties and the need for speech services in school-aged children with cleft palate. METHODS: Participants included 100 school-aged children with cleft palate. Americleft speech protocol was used to assess the perceptual aspects of speech production. The logistic regression was performed to evaluate the impact of independent variables (IV) on the dependent variables (DV): intelligibility, posterior oral CSCs, audible nasal emission, hypernasality, anterior oral CSCs, and speech therapy required. RESULTS: Sixty-five percent of the children were enrolled in (or had received) speech therapy. The logistic regression model shows a good fit to the data for the need for speech therapy (Hosmer and Lemeshow's χ2(8)=9.647,p=.291). No IVs were found to have a significant impact on the need for speech therapy. A diagnosed syndrome was associated with poorer intelligibility (Pulkstenis-Robinson's χ2(11)=7.120,p=.789). Children with diagnosed syndromes have about six times the odds of a higher hypernasality rating (Odds Ratio = 5.703) than others. The cleft type was significantly associated with audible nasal emission (Fisher'sexactp=.006). At the same time, malocclusion had a significant association with anterior oral CSCs (Fisher'sexactp=.005). CONCLUSIONS: According to the latest data in the Cleft Registry and Audit Network Annual Report for the UK, the majority of children with cleft palate attain typical speech by age five. However, it is crucial to delve into the factors that may influence the continuation of speech disorders beyond this age. This understanding is vital for formulating intervention strategies aimed at mitigating the long-term effects of speech disorders as individuals grow older.

Relationship between COVID-19 and orofacial clefts.

The work presents the connection between the infection of COVID-19 during pregnancy and non-syndromic orofacial clefts (NSOFC). Aim of the study was to compare the incidence of COVID-19 disease during mother´s pregnancy between a group of the children with NSOFC and a control group of the children without NSOFC. COVID-19 was confirmed by polymerase chain reaction (PCR) test. The study showed significantly higher incidence of COVID-19 disease in the group of mothers who gave birth to a child with NSOFC in comparison to the group of mothers who gave birth to a child without NSOFC. Our results indicate the possible participation of the infection of COVID-19 in the formation of NSOFCs.

Craniofacial morphological variability in orthodontic patients with non-syndromic orofacial clefts: an approach using geometric morphometrics.

OBJECTIVES: Orofacial clefts are complex congenital anomalies that call for comprehensive treatment based on a thorough assessment of the anatomy. This study aims to examine the effect of cleft type on craniofacial morphology using geometric morphometrics. MATERIALS AND METHODS: We evaluated lateral cephalograms of 75 patients with bilateral cleft lip and palate, 63 patients with unilateral cleft lip and palate, and 76 patients with isolated cleft palate. Generalized Procrustes analysis was performed on 16 hard tissue landmark coordinates. Shape variability was studied with principal component analysis. In a risk model approach, the first nine principal components (PC) were used to examine the effect of cleft type. RESULTS: We found statistically significant differences in the mean shape between cleft types. The difference is greatest between bilateral cleft lip and palate and isolated cleft palate (distance of means 0.026, P = 0.0011). Differences between cleft types are most pronounced for PC4 and PC5 (P = 0.0001), which together account for 10% of the total shape variation. PC4 and PC5 show shape differences in the ratio of the upper to the lower face, the posterior mandibular height, and the mandibular angle. CONCLUSIONS: Cleft type has a statistically significant but weak effect on craniofacial morphological variability in patients with non-syndromic orofacial clefts, mainly in the vertical dimension. CLINICAL RELEVANCE: Understanding the effects of clefts on craniofacial morphology is essential to providing patients with treatment tailored to their specific needs. This study contributes to the literature particularly due to our risk model approach in lieu of a prediction model.

"Long term speech outcomes after using the Sommerlad technique for primary palatoplasty: a retrospective study in the Wilhelmina Children's Hospital, Utrecht."

OBJECTIVES: After cleft lip and/or palate (CL/P) repair, children may develop velopharyngeal insufficiency (VPI) leading to speech imperfections, necessitating additional speech correcting surgery. This study examines the incidence of VPI and speech correcting surgery after Sommerlad's palatoplasty for CL/P, and its association with various clinical features. MATERIALS AND METHODS: A retrospective cohort study was performed in the Wilhelmina Children's Hospital in Utrecht and child records from 380 individuals with CL/P registered from 2008 to 2017 were retrospectively reviewed. Inclusion criteria comprised the diagnosis of CL/P, primary palatoplasty according to Sommerlad's technique, and speech assessment at five years or older. Association between cleft type and width, presence of additional genetic disorders and postoperative complications (palatal dehiscence, fistula) were assessed using odds ratios and chi squared tests. RESULTS: A total of 239 patients were included. The VPI rate was 52.7% (n = 126) and in 119 patients (49.8%) a speech correcting surgery was performed. Severe cleft type, as indicated by a higher Veau classification, was associated with a significant higher rate of speech correcting surgeries (p = 0.033). Significantly more speech correcting surgeries were performed in patients with a cleft width >10 mm, compared to patients with a cleft width ≤10 mm (p < 0.001). Patients with oronasal fistula underwent significantly more speech correcting surgeries than those without fistula (p = 0.004). No statistically significant difference was found in the incidence of speech correcting surgery between patients with and without genetic disorders (p = 0.890). CONCLUSIONS/CLINICAL RELEVANCE: Variations in cleft morphology, cleft width and complications like oronasal fistula are associated with different speech outcomes. Future research should focus on creating a multivariable prediction model for speech correcting surgery in CL/P patients.

[Gene-gene/gene-environment interaction of transforming growth factor-ß signaling pathway and the risk of non-syndromic oral clefts].

OBJECTIVE: To explore the association between polymorphisms of transforming growth factor-ß (TGF-ß) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. METHODS: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-ß signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. RESULTS: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. CONCLUSION: The comprehensive evaluation of SNP associations and interactions within the TGF-ß signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-ß signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Book-Sharing for Toddlers with Clefts (BOOST): Protocol for a randomized controlled trial of a remote intervention to promote language development in children with cleft palate.

BACKGROUND: Children with cleft palate, with or without cleft lip (CP±L), exhibit language delays on average compared to children without clefts. Interventions to address these disparities are scarce. In this multi-center study, Book Sharing for Toddlers with Clefts (BOOST), we will test a remote, parent-focused intervention to promote language development in children with CP±L. OBJECTIVES: The study will test two primary hypotheses. First, toddlers randomized to BOOST will exhibit better language outcomes than children receiving standard-of-care (SOC). Second, we hypothesize that the BOOST program's effect on language outcomes is mediated by the frequency and quality of parent-child reading interactions. METHODS: The study is a randomized-controlled trial comparing the BOOST group to a SOC comparison group. We will enroll N = 320 English and/or Spanish-speaking children ages 24-32 months with isolated CP±L (n = 160 per group). Both groups will receive children's books, and parents will record and upload videos of themselves reading the books with their children using a smartphone app developed for the study. Parents will also complete surveys asking whether they read to their children on five randomly selected days each week. In addition, the BOOST group will participate in 3 remote dialogic book-sharing intervention sessions via Zoom. We will code book-sharing videos to assess parents' target skill usage and children's expressive language. End-of-study assessments will include measures of child language outcomes (e.g., clinician-administered measures, parent reports, and naturalistic child language samples). RESULTS: Enrollment began in April 2024 and will continue through approximately April 2028. CONCLUSION: The BOOST study will address a critical gap in the literature on interventions to improve language in children with CP±L. The results will inform the care for toddlers with oral clefts and have potential applications for other populations.

Prevalence and clinical characterization of oral clefts in patients with chromosome trisomy 18.

OBJECTIVE: To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil. METHODS: This was a retrospective cross-sectional study, performed in a reference clinical genetic service in Southern Brazil. The initial sample consisted of 77 patients diagnosed in the neonatal period with trisomy 18 treated at the Clinical Genetics Service of a referral hospital at Federal University of Health Sciences of Porto Alegre (UFCSPA). The patients' diagnosis was confirmed by karyotype and care was provided during their stay in the intensive care unit (ICU) of the hospital that is a reference in Southern Brazil for care for malformed patients. The period covered was from 1975 to 2020. RESULTS: During the study period, 77 patients diagnosed with trisomy 18 were treated, most of them in the ICU. Of these, 13 individuals were excluded due to incomplete data. The final sample consisted of 64 patients with an average age of 2.4 years of life, ranging from one day to 16 years old, the majority of whom were female. Regarding face dysmorphisms identified in the sample, three (4,68%) patients had cleft lip and two (3,11%) had cleft lip and palate. CONCLUSIONS: This study contributed to the recognition of the characteristics and prevalence of oral clefts in individuals with trisomy 18 in a sample of patients from Southern Brazil. In addition, we described the clinical alterations found in patients with oral clefts, as well as other associated comorbidities, such as cardiac, neurological and pulmonary comorbidities, as well as cranial and facial dysmorphisms.

Translation and validation of the French version of the child perceptions questionnaire for children aged 11 to 14 years old (CPQ11-14) short-form.

OBJECTIVES: The COHQoL is a set of questionnaires used to evaluate the impact of oral health on children's quality of life. Although the CPQ8-10 and the P-CPQ have been translated and validated in French, the CPQ11-14 14 has not yet been validated. The aim was to develop a French version of the CPQ11-14 16-items. MATERIALS AND METHODS: The French version of CPQ11-14 was obtained by a forward-backward translation process and pretested. The final version was tested on children aged 11-14 and divided into three groups: children with orofacial clefts, children with rare dental diseases other than clefts, and children without anomalies. We conducted a cross-sectional study and evaluated the reliability with test-retest and internal consistency, and the questionnaire validity with construct validity and discriminant validity. We performed an Exploratory Factory Analysis (EFA). RESULTS: 187 children tested the questionnaire. The ICC of the test-retest was 0.76 and the Cronbach's alpha was 0.77. The correlation between the CPQ11-14 and self-assessment of oral health and general well-being was > 0.2. Patients with orofacial clefts and rare diseases had significantly higher scores for overall short-form CPQ11-14. The EFA revealed six factors. CONCLUSION: The French CPQ11-14 is valid to assess the impact of oral health on children's quality of life. CLINICAL RELEVANCE: The translation of this questionnaire into French will enable us to assess the impact of oral health on the quality of life of adolescents. This questionnaire complements the 8-10 years version of the CPQ, as well as the parental version that can be used in conjunction with the questionnaire.

Rare variants analyses suggest novel cleft genes in the African population.

Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E-04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.

Laser therapy for treating cleft lip or/and palate scarring-a systematic review and meta-analysis.

This review aims to assess the efficacy and safety of laser therapy in managing scars resulting from cleft lip and/or palate (CL/P) repair surgeries, as well as to determine the optimal timing for intervention. A systematic search was conducted across four databases using a predefined search strategy. Studies included were randomized controlled trials, non-randomized studies, and case series focusing on laser therapy for CL/P scars. Data extraction and analysis were performed using Revman Software. A total of two randomized controlled trials, four non-randomized studies, and three case series were included in the analysis. The fractional CO2 laser was the most commonly utilized type of laser. Following laser therapy, there was a significant decrease in Vancouver Scar Scale (VSS) scores by 4.05 (95% CI, 2.10-5.99). Meta-analysis revealed that laser treatment groups exhibited a significantly lower mean VSS score (1.3; 95% CI, 0.02-2.67) compared to control groups. Moreover, initiating laser therapy intervention at one month postoperatively resulted in a significantly lower VSS score compared to initiation at three months postoperatively (difference of 1.70; 95% CI, 1.33-2.08). No severe complications were reported. Laser therapy demonstrates effectiveness and safety in improving CL/P scars, with earlier intervention yielding greater benefits.

[Universal scoring system for assessing speech function in patients with cleft palate at the stages of surgical treatment]. / Universal'naya ball'naya sistema otsenki rechevoi funktsii u patsientov s rasshchelinoi neba na etapakh khirurgicheskogo lecheniya.

OBJECTIVE: To develop a universal system for assessing the speech function in patients with congenital palatal cleft in the postoperative period. MATERIALS AND METHODS: A universal system for assessing the speech function for patients with a palatal cleft can be applied both after the primary operation of uranoplasty and for patients diagnosed with velopharyngeal insufficiency (VPI). The patient's speech is assessed according to the following criteria: defects in the pronunciation of consonants by place of articulation: labial, labiodental, lingual-dental, lingual-palatal, lingual-alveolar; speech breathing; tongue position; directed air stream; voicing disorders; The patient's is also evaluated for the following findings: hypernasality (reflected speech); hypernasality (spontaneous speech); hyponasality; pharyngeal reflex; audible nasal emission/turbulence; facial grimaces; speech intelligibility. The speech therapy and dental assessments are added to obtain a value characterizing the patient's condition: from 0 to 10 scoring indicates than only speech therapy correction is needed; from 11 to 18 - the decision on the necessity of surgical treatment is made by the surgeon together with the speech therapist, from 18 to 25 - surgical treatment is necessary with subsequent sessions with a speech therapist. RESULTS: With the help of this questionnaire, the operating surgeon can more accurately and objectively assess in dynamics the result of the surgical treatment, regardless of the results of speech therapy treatment in the postoperative period. The creation of this scoring system for speech assessment is aimed at objectivizing the results of uranoplasty and speech-improving operations. It allows the surgeon to compare the effectiveness of different surgical methods. CONCLUSION: The universal scoring system for assessing the state of speech function can be applied in the diagnosis of a patient with a palatal cleft both after the primary operation on the palate and after corrective surgical interventions. It allows monitoring progress and identifying dynamics in surgical and speech therapy treatment.

Evaluation of platelet-rich fibrin versus collagen membrane for enhancing healing of secondary grafted alveolar cleft: a randomised controlled trial.

The purpose of this study was to compare the efficiency of using autologous platelet-rich fibrin versus a resorbable collagen membrane in secondary alveolar bone grafting. Patients were randomly allocated to the three treatment groups: Group 1 - twelve children in whom the nasal layers of the alveolar clefts were repaired using autologous platelet-rich fibrin with autogenous chin bone; Group 2 - twelve children in whom the nasal layers of the alveolar clefts were repaired using bovine collagen membrane type I (Colla-D) with autogenous chin bone; and Group 3 - twelve children in whom the bony alveolar clefts were grafted with autogenous chin bone after construction of a watertight nasal floor had been completed. The study population comprised 36 patients with alveolar clefts, ranging in age from seven to 12 years. At the last follow-up period all groups had stable healing conditions and good radiological outcomes in terms of the alveolar bone height bordering the teeth (both mesially and distally) and the incorporation of grafting material with the surrounding bone. The use of either a PRF membrane and a collagen membrane as an interpositional layer between the nasal layer and the autogenous chin bone graft enhanced bone formation and density in alveolar clefts compared with the control group.

Surgical Treatment of Lip Pits in Van der Woude Syndrome: A Preliminary Retrospective Study of 24 Patients.

BACKGROUND: Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity. METHODS: The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients. RESULTS: In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome. CONCLUSIONS: The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low.