Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

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

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

The cleft lip and palate (CLP) is one of the most common craniofacial malformations in humans. We collected functional magnetic resonance data of 23 CLP patients before rehabilitation training (Bclp) and 23 CLP patients after rehabilitation training (Aclp), who were performing Chinese character pronunciation tasks, and performed brain activation analysis to explore the changes of brain mechanism in CLP patients after articulation disorder rehabilitation training. The study found that Aclp group had significant activation in the motor cortex, Broca area, Wernicke area and cerebellum. While the Bclp group had weak activation in the motor cortex with a small activation range. By comparing the differences and co-activated brain regions between the two groups, we found that rehabilitation training increased the activity level of negatively activated brain areas (cerebellum, left motor area, Wernicke area, etc.) to a positive level. At the same time, the activity level of weakly activated brain areas (right motor area, Broca area, etc.) was also increased. Rehabilitation training promoted the activity level of articulation-related brain regions. So that the activation intensity of articulation-related brain regions can be used as a quantifiable objective evaluation index to evaluate the effect of rehabilitation training, which is of great significance for the formulation of rehabilitation training programs.
Humans ; Articulation Disorders/therapy* ; Brain/diagnostic imaging* ; Cleft Lip/diagnostic imaging* ; Cleft Palate/diagnostic imaging* ; Magnetic Resonance Imaging ; Speech Therapy/psychology*

Objective: To measure and analyze the morphometric changes in the anterior alveolar bone during treatment and retention stage after retraction in bimaxillary adults using cone-beam CT(CBCT). Methods: Fifteen adult patients, four males and 11 females, aged 19 to 28 years[(22.2±3.1) years], who have completed orthodontic treatment and extracted four first premolar teeth for retraction in the Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University from January 2016 to December 2018 were selected. CBCT was taken to assess the labial and palatal vertical bone level, total bone thickness at crest area, middle root area and apical area in pre-treatment (T1), post-treatment (T2) and at follow-up (maintained for more than two years) (T3). The differences in alveolar bone morphology at different stages were compared by single factor repeated measure ANOVA, and Pearson correlation analysis was performed on the amount of alveolar bone change in treatment stage and retention stage. Results: There were statistically significant differences in the alveolar bone height of the palatal side of maxillary anterior teeth, the labial side of maxillary lateral incisors and canine among three time points (P<0.05). The height difference of palatal alveolar bone of anterior teeth in T1-T2 stage was statistically significant (P<0.05). Palatal alveolar bone of upper and lower central incisors decreased by (1.52±0.32) and (4.96±0.46) mm, respectively. The height difference of anterior palatal alveolar bone was statistically significant in T2-T3 stage(P<0.05), the palatal alveolar bone height of central incisors increased by (1.20±0.27) and (3.14±0.35) mm respectively. The height difference of palatal alveolar bone in the anterior teeth of T1-T3 stage was statistically significant (P<0.05), and the height of palatal alveolar bone of central incisors was decreased (0.33±0.11) and (1.82±0.39) mm, respectively. There were statistically significant differences in the thickness of the cervical and middle root alveolar bone of anterior teeth among three time points (P<0.05). The difference of alveolar bone thickness of the cervical and middle root of anterior teeth at T1-T2 was statistically significant (P<0.05). decreased by (0.63±0.10) and (0.67±0.09) mm in lateral incisors, respectively. In the T2-T3 stage, the alveolar bone thickness of the crest area of the lower anterior teeth was significantly different (P<0.05), the alveolar bone thickness of mandibular central incisor crest area increased (0.09±0.03) mm. There were statistically significant differences in alveolar bone thickness in crest area and middle root of the incisors during T1-T3 stage (P<0.05), among which the middle root decreased by (0.38±0.16) mm and (0.63±0.13) mm, respectively. There was no statistically significant difference in other areas (P>0.05). The change of alveolar bone height in palatal side of upper anterior teeth at T2-T3 was very strongly negatively correlated with the change in T1-T2. The change of alveolar bone height in labial side of upper anterior teeth and lingual side of lower anterior teeth and the thickness of incisor root and neck were moderately strongly negatively correlated (r≤-0.8, P<0.001), the change of alveolar bone height in labial side of upper anterior teeth and lingual side of lower anterior teeth and the thickness of incisor crest area were moderately strongly negatively correlated (-0.8<r≤-0.4, P<0.05). Conclusions: For adult patients after retraction, anterior alveolar bone decreased significantly. In the retention stage, the same degree of bone apposition will occur, but still have alveolar bone loss compared with pre-treatment. The amount of alveolar bone change in the retention stage correlated with the amount of alveolar bone change in the treatment stage.
Male ; Female ; Humans ; Maxilla/diagnostic imaging* ; Cone-Beam Computed Tomography ; Tooth Root ; Malocclusion ; Palate

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common sleep respiratory disorder characterized by upper respiratory collapse during sleep, with a high prevalence and potentially fatal complications. Currently, maxillary transverse deficiency are considered to be an important pathogenic factor of OSAHS. For patients with poor compliance with positive airway pressure therapy, rapid maxillary expansion can increase the volume and ventilation of the upper respiratory tract, which is an alternative treatment. This paper reviewed the current research on surgically assisted rapid palatal expansion, miniscrew assisted rapid palatal expansion, and distraction osteogenesis maxillary expansion in the treatment of adult OSAHS. By comparing the indications, contraindications, complications, efficacy and long-term stability of the three treatment methods, it provided reference for treatment of patients with OSAHS.
Adult ; Humans ; Nose ; Palatal Expansion Technique ; Palate ; Sleep Apnea, Obstructive/surgery* ; Syndrome

Alveolar cleft is one of the key links of cleft lip and palate reconstruction due to its close relationship with tooth and jaw coordination and nasolabial deformity. The alveolar bone graft repairs the hole in the gum ridge and stabilizes the bone arch, providing better support for the base of the nose and new bone for the roots of the developing teeth to grow into. Unfortunately, bone graft failure in the traditional way, even among minor clefts, bony hypoplasia, or absence that affects the nasal base and piriform rim, is common. Two-stage alveolar bone grafting, which has advantages in addressing the underlying skeleton and deficiency, could be an optional surgical procedure for nasal floor reconstruction in adult patients with a broad alveolar cleft.
Humans ; Adult ; Alveolar Bone Grafting/methods* ; Cleft Lip/surgery* ; Cleft Palate/surgery* ; Treatment Outcome ; Nose/abnormalities* ; Bone Transplantation/methods*

OBJECTIVES: To review the effectiveness of secondary alveolar bone grafting using iliac cancellous bone in patients with unilateral complete alveolar cleft and to investigate the factors influencing it. METHODS: A retrospective study of 160 patients with unilateral complete alveolar clefts who underwent iliac cancellous bone graft repair at the Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, was conducted. Eighty patients in the young age group (6-12 years) and 80 in the old age group (≥13 years) were included. Bone bridge formation was determined using Mimics software, and the volume was measured to calculate the iliac implantation rate, residual bone filling rate, and resorption rate. The factors that affected bone grafting in both subgroups were investigated. RESULTS: Using bone bridge formation as the clinical success criterion, the success rate for the entire population was 71.25%, with a significant difference of 78.75% and 63.75% for the young and old age groups, respectively (P=0.036). The gap volume in the latter was significantly larger than that in the former (P<0.001). The factors that influenced bone grafting in the young group were the palatal bone wall (P=0.006) and history of cleft palate surgery (P=0.012), but only the palatal bone wall affected the outcome in the old age group (P=0.036). CONCLUSIONS The results of alveolar bone grafting for the old age group were worse than those for the young age group. The palatal bone wall was an important factor that affected alveolar bone grafting, and alveolar bone grafting in the young patients was influenced by the history of cleft palate surgery.
Humans ; Child ; Adolescent ; Cleft Palate/surgery* ; Cleft Lip/surgery* ; Retrospective Studies ; Cancellous Bone ; Treatment Outcome ; Alveolar Bone Grafting/methods* ; Bone Transplantation/methods*

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.
Humans ; Connective Tissue/transplantation* ; Palate ; Collagen ; Fibroblasts ; Signal Transduction

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