BACKGROUND: An increased prevalence of cleft lip and/or palate (CL/P), a major congenital anomaly, has been observed in the offspring of women with elevated body mass index (BMI) before pregnancy. Likewise, gestational comorbidities, such as hypertension and diabetes mellitus, also increase the risk of CL/P; however, the risk linked to the coexistence of these conditions in women with higher BMI on birth prevalence of CL/P remains unclear. This study focused on the combined effects of a high BMI before pregnancy and gestational comorbidities on the birth prevalence of CL/P. METHODS: Among 98,373 live births from the Japan Environment and Children's Study (JECS), a nationwide birth cohort, 255 mothers of infants with CL/P (74, 112, and 69 infants born with cleft lip, cleft lip and palate, and isolated cleft palate, respectively) were included in the analyses. The association of CL/P birth prevalence with pre-pregnancy BMI and gestational comorbidities (hypertension and diabetes) was examined using multivariate logistic regression analyses after multiple imputations, with adjustments for several maternal (age at delivery, smoking habits, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables, obtained through medical record transcriptions and self-reports on JECS transcription forms. RESULTS: Higher prevalence rates of overweight, gestational hypertension, and gestational diabetes mellitus were found in mothers of infants with CL/P (16.1%, 6.3%, and 4.7%, respectively) than in the control group (10.4%, 3.1%, and 3.1%, respectively). The odds ratio [95% confidence interval] for childbirth with CL/P was increased in mothers with high BMI before pregnancy (1.58 [1.11-2.24]). Furthermore, gestational hypertension and diabetes coexisting with high BMI additionally increased the odds ratios for childbirth with CL/P (2.91 [1.28-6.61] and 2.12 [0.87-5.19], respectively). CONCLUSION High maternal BMI, particularly when accompanied by gestational hypertension, was significantly associated with an increased prevalence of childbirth with CL/P.
Humans ; Female ; Cleft Lip/etiology* ; Cleft Palate/etiology* ; Pregnancy ; Japan/epidemiology* ; Prevalence ; Body Mass Index ; Adult ; Male ; Infant, Newborn ; Comorbidity ; Diabetes, Gestational/epidemiology* ; Risk Factors ; Young Adult ; Birth Cohort

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

OBJECTIVES: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population. METHODS: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association. PLINK software was used to perform Hardy-Weinberg equilibrium (HWE) test. Association analysis for common variants, gene burden analysis for rare mutations, and function prediction of SNPs with non-synonymous mutations were performed using Mutation Taster and other software programs. RESULTS: In the first stage, 126 variants, including 76 single nucleotide variants and 50 insertion-deletions were identified. All the included SNPs confirmed to HWE, and the results of gene burden analysis and prediction of functional harmfulness for rare variants were not statistically significant. Association analysis showed that rs13292899 of the FOXE1 gene was significantly associated with NSCL/P (P=1.85E-27) and was also correlated with NSCLO (P=6.41E-23) and non-syndromic cleft lip with cleft palate (NSCLP) (P=2.36E-15) subtypes. In the validation phase, rs79268293 (P=0.013, P=0.022), rs10983951 (P=0.009 2, P=0.007 6), rs117227387 (P=0.009 2, P=0.007 6), rs3758250 (P=0.009 2, P=0.007 6), and rs116899397 (P=0.009 2, P=0.007 6) were significantly associated with NSCLO and NSCPO; rs13292899 (P=0.008 5), rs74606599 (P=0.008 3), rs143226042 (P=0.008 3), and rs117236550 (P=0.01) were associated with the occurrence of NSCLO; and rs12343182 (P=0.008 7), rs10119760 (P=0.012), rs10113907 (P=0.012), and rs13299924 (P=0.012) were associated with the occurrence of NSCPO. CONCLUSIONS This study found a new susceptible SNP rs13292899 of the FOXE1 gene that is closely associated with NSCL/P and NSCLO subtype and 13 other SNPs associated with NSCLO or NSCPO.
Female ; Humans ; Male ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Forkhead Transcription Factors/genetics* ; Haplotypes ; Polymorphism, Single Nucleotide ; East Asian People/genetics*

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

The unilateral cleft lip repair surgery has undergone over a century of development, marked by achievements and difficulties. Although the development of the methods for cleft lip repair has passed the period of rapid advancement, there remains an urgent need in clinical practice to further improve these methods in order to enhance clinical outcomes. This article aims to improve cleft lip repair methods by analyzing and elaborating on various aspects, including the attributes of cleft lip repair, the shift in concepts of cleft lip repair, innovations in surgical techniques, technical improvements, and classifications and repair methods for correcting secondary deformities. The analysis is based on the author's research and experience.
Cleft Lip/surgery* ; Humans ; Plastic Surgery Procedures/methods* ; Surgical Flaps

Background: One of the early problems that children born with cleft lip and palate encounter is difficulty in feeding. This affects the child’s nutritional needs and the timing of the surgical intervention. Information on the appropriate feeding methods for children with cleft lip and palate will enable mothers to feed their babies properly and facilitate the implementation of appropriate interventions. Objectives: The study described the feeding problems experienced by children with cleft lip and palate (CLP), and cleft palate (CP) ages 0-24 months, the feeding methods most preferred by Filipino mothers, the methods they found most useful, and the mothers’ reactions to the feeding issues their children face. Methods. The research is a pilot study which used a quantitative, cross-sectional, descriptive mixed method design. Thirty-two (32) mothers of children with cleft lip and palate, and cleft palate answered an 11-item online survey and participated in focused interviews from January to June 2022. Inferential statistics was used specifically frequency distribution to describe the data, and Fishers’ Exact Test and Pearson’s Chi-Square Test were used to analyze the data quantitatively to determine the significant association between the variables identified. Results: Results showed that the feeding problems encountered by the children included nasal regurgitation, sucking, aspiration of liquids, latching on nipples, and swallowing. Mothers preferred to use regular feeding bottles (24.3%), specialized feeding bottles for children with cleft (21.6%), breast feeding and dropper (17.6%), syringe (9.5%), cup (6.8%), and spoon feeding (2.7%) methods. They also mentioned that they found the following feeding methods to be the most useful, regular feeding bottles (32.7%), specialized feeding bottles for cleft (23.1%), breast feeding (11.5%), spoon and dropper feeding (7.7%), and syringe feeding (1.9%). Conclusion The feeding problems experienced by Filipino children with CLP and CP mirror those that have been reported in other studies. The study revealed that mothers still prefer to use the traditional regular feeding bottles in feeding their babies and found this to be the most useful. Maternal reactions of the participants to the cleft condition and its feeding issues are similar to reported studies in other countries. The internet has been the primary source of information on cleft and feeding of the participants in the study.
Feeding Methods ; Cleft Lip ; Palate

OBJECTIVE: To investigate the effectiveness of comprehensive rhinoplasty with autogenous costal cartilage grafting and prosthesis augmentation rhinoplasty in the treatment of secondary nasal deformity with saddle nasal deformity after cleft lip surgery. METHODS: The clinical data of 96 patients with secondary nasal deformity with saddle nasal deformity after cleft lip surgery between September 2008 and January 2019 were retrospectively analyzed. There were 17 males and 79 females with an average age of 25.6 years (range, 17-38 years). Autogenous costal cartilage grafts were used to construct stable nasal tip framework and enhance the strength of alar cartilage. Nasal dorsum prostheses (39 cases of bulge, 45 cases of silicone prosthesis) or autogenous costal cartilage (12 cases) were used for comprehensive rhinoplasty. Visual analogue scale (VAS) score was used to evaluate the postoperative satisfaction subjectively, and nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle were calculated to evaluate objectively before and after operation. RESULTS: All patients were followed up 6 months to 8 years, with an average of 13.4 months. Nasal septal hematoma occurred in 3 patients after operation, which was improved after local aspiration and nasal pressure packing. Two cases had mild deformation of the rib cartilage graft of the nasal dorsum, one of which had no obvious deviation of the nasal dorsum and was not given special treatment, and one case underwent the cartilage graft of the nasal dorsum removed and replaced with silicone prosthesis. The incisions of the other patients healed by first intention, and there was no complication such as postoperative infection and prosthesis displacement. The nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle significantly improved after operation when compared with preoperative ones ( P<0.05). Postoperative subjective satisfaction evaluation reached the level of basic satisfaction or above, and most of them were very satisfied. CONCLUSION Comprehensive rhinoplasty using autologous rib cartilage grafting to construct a stable nasal tip support, combined with dorsal nasal prosthesis or autologous cartilage implantation, can achieve good effectiveness on secondary nasal deformity with saddle nasal deformity after cleft lip surgery.
Male ; Female ; Humans ; Adult ; Rhinoplasty ; Cleft Lip/surgery* ; Retrospective Studies ; Nose/surgery* ; Nasal Septum/surgery* ; Nasal Cartilages/surgery* ; Silicones ; Treatment Outcome

The maxillofacial region has multiple functions such as breathing, language, and facial expressions. Children's maxillofacial development is a complex and long process, which is affected by many factors such as genetics, diseases, bad habits and trauma. Early detection, early diagnosis, and early treatment are important concepts in children's maxillofacial management. Digital technology medicine is an emerging technology based on medical imaging and anatomy that has emerged in recent years. The application of this technology in the field of clinical medicine will undoubtedly bring great benefits to children's maxillofacial management. This article summarizes the research on digital technology in children's maxillofacial management, and focuses on the research on children's malocclusion, children's OSA, cleft lip and palate and other related diseases.
Humans ; Child ; Cleft Lip/surgery* ; Cleft Palate/surgery* ; Digital Technology ; Respiration

OBJECTIVES: Currently, the research results regarding the bilateral temporomandibular joint symmetry in patients at different ages with unilateral complete cleft lip and palate (UCLP) are still controversial. In this study, the position of condyle in the articular fossa and morphology of condyle in UCLP patients at different developmental stages was measured and analyzed to explore the asymmetry difference, which can provide a new theoretical basis for the sequential therapy. METHODS: A total of 90 patients with UCLP were divided into a mixed dentition group (31 cases), a young permanent dentition group (31 cases) and an old permanent dentition group (28 cases) according to age and dentition development. Cone beam computed tomography (CBCT) images were imported into Invivo5 software for 3D reconstruction, and the joint space, anteroposterior diameter, medio-lateral diameter, and height of condylar were measured, and its asymmetry index was calculated. RESULTS: The asymmetry index of condylar height and anteroposterior diameter among the 3 groups, from small to large, was the mixed dentition groupP<0.05). There was no significant difference in condylar anteroposterior diameter and asymmetry index between the mixed dentition group and the young permanent dentition group (both P>0.05), all of them were lower than those in the old permanent dentition group (both P<0.05). Compared with the normal side, the height of fracture condyle was smaller among the 3 groups (all P<0.05), and the anterior joint space was smaller (P<0.05) and the posterior joint space was larger (P<0.05) in the mixed dentition group. CONCLUSIONS In patients with UCLP, the asymmetry of condylar morphology increases with age, but the condylar position tends to normal. These results suggest that early treatment has important clinical significance for the morphologic development of temporomandibular joint in UCLP patients.
Humans ; Cleft Lip/diagnostic imaging* ; Cleft Palate/diagnostic imaging* ; Temporomandibular Joint/diagnostic imaging* ; Clinical Relevance

The cranial neural crest plays a fundamental role in orofacial development and morphogenesis. Accordingly, mutations with impact on the cranial neural crest and its development lead to orofacial malformations such as cleft lip and palate. As a pluripotent and dynamic cell population, the cranial neural crest undergoes vast transcriptional and epigenomic alterations throughout the formation of facial structures pointing to an essential role of factors regulating chromatin state or transcription levels. Using CRISPR/Cas9-guided genome editing and conditional mutagenesis in the mouse, we here show that inactivation of Kat5 or Ep400 as the two essential enzymatic subunits of the Tip60/Ep400 chromatin remodeling complex severely affects carbohydrate and amino acid metabolism in cranial neural crest cells. The resulting decrease in protein synthesis, proliferation and survival leads to a drastic reduction of cranial neural crest cells early in fetal development and a loss of most facial structures in the absence of either protein. Following heterozygous loss of Kat5 in neural crest cells palatogenesis was impaired. These findings point to a decisive role of the Tip60/Ep400 chromatin remodeling complex in facial morphogenesis and lead us to conclude that the orofacial clefting observed in patients with heterozygous KAT5 missense mutations is at least in part due to disturbances in the cranial neural crest.
Animals ; Mice ; Chromatin Assembly and Disassembly ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; DNA Helicases/metabolism* ; DNA-Binding Proteins ; Neural Crest/metabolism* ; Skull ; Transcription Factors/metabolism*