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

Objective:To investigate the management of granulation tissue during surgery for infected congenital preauricular fistula and to assess the surgical outcomes. Methods:To summarize the surgical methods and the treatment of granulation methods in 140 cases of congenital preauricular fistula during the period of infection treated in our department from January 2018 to September 2022. The study divided patients into an observation group （79 patients） undergoing fistulectomy without granulation treatment, and a control group （61 patients） where fistulectomy and granulation resection were performed concurrently.. After six months of follow-up, the wound healing, recurrence rates, and the aesthetic assessment of granulation healing were evaluated using the Stony Brook Scar Evaluation Scale（SBSES）. Results:The two surgical approaches were applied to a total of 140 patients with infected congenital preauricular fistula. There was no statistical difference in wound healing and recurrence rates between the observation group and the control group. However, the observation group exhibited smaller scars. Conclusion:In cases of infected congenital preauricular fistula, surgical removal without excising granulation tissue is feasible, leading to effective healing and lesser scar formation.
Humans ; Cicatrix ; Wound Healing ; Craniofacial Abnormalities ; Fistula/surgery* ; Treatment Outcome

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

OBJECTIVES: This study aimed to explore the relationship between alveolar cleft and secondary nasal deformity post unilateral cleft lip repair in adults. METHODS: A total of 27 patients aged 16-30 years old with unilateral secondary nasal deformity and alveolar cleft were included, 13 of whom underwent bone grafting. Spiral CT data of all preoperative and postoperative patients who had alveolar bone grafting were collected. Then, Mimics software was used for three-dimensional reconstruction to evaluate the correlation between the width, height, and volume of the alveolar cleft and those of the nasal deformity. The difference in nasal deformity before and after alveolar bone grafting was also explored. RESULTS: The width of the alveolar cleft was positively correlated with the difference in bilateral nostril floor width (P<0.05). As the effective depth of the alveolar cleft increased, the sub-alare inclination angle largened (P<0.05). However, no significant difference was found in the nasal deformity between before and after alveolar bone grafting. CONCLUSIONS Alveolar cleft is closely related to secondary nasal deformities post unilateral cleft lip repair, especially nasal floor deformities. Alveolar bone grafting benefits adult patients for the improvement of secondary nasal deformities post unilateral cleft lip repair.
Humans ; Adult ; Adolescent ; Young Adult ; Nose/surgery* ; Cleft Lip/surgery* ; Rhinoplasty/methods* ; Imaging, Three-Dimensional ; Treatment Outcome ; Cleft Palate/complications*

OBJECTIVE: To preliminarily verify the effectiveness of self-designed artificial condyle-mandibular distraction (AC-MD) complex in the treatment of Pruzansky type ⅡB and Ⅲ hemifacial microsomia (HFM) through model test. METHODS: Five children with Pruzansky type ⅡB and Ⅲ HFM who were treated with mandibular distraction osteogenesis (MDO) between December 2016 and December 2021 were selected as the subjects. There were 3 boys and 2 girls wih an average age of 8.4 years (range, 6-10 years). Virtual surgery and model test of AC-MD complex were performed according to preoperative skull CT of children. The model was obtained by three-dimensional (3D) printing according to the children's CT data at a ratio of 1∶1. The occlusal guide plate was designed and 3D printed according to the children's toothpaste model. The results of the model test and the virtual surgery were matched in three dimensions to calculate the error of the residual condyle on the affected side, and the model test was matched with the actual skull CT after MDO to measure and compare the inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible. RESULTS: The error of residual condyle was (1.07±0.78) mm. The inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible after 3D printing model test were significantly larger than those after MDO ( P<0.05). CONCLUSION In the model test, the implantation of AC-MD complex can immediately rotate the mandible to the horizontal position and improve facial symmetry, and the residual condyle segment can be guided close to the articular fossa or the preset pseudoarticular position of the skull base after operation.
Male ; Child ; Female ; Humans ; Goldenhar Syndrome/surgery* ; Mandible/surgery* ; Osteogenesis, Distraction/methods* ; Printing, Three-Dimensional ; Facial Asymmetry/surgery*

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant with craniosynostosis. METHODS: An infant who was admitted to Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in April 2021 due to widening of the lateral ventricles for over a month was selected as the study subject. Clinical data of the patient was collected. Peripheral blood samples were collected from the infant and her parents for chromosomal karyotyping and whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was retrieved from the PubMed, Wanfang and CNKI databases (up to December 2021) by using key words including ERF gene, craniosynostosis, ERF mutation, craniosynostosis and ERF-related craniosynostosis. RESULTS: The infant, a 1-month-and-16-day-old female, was found to have sagittal synostosis by cranial X-ray radiography. Genetic testing revealed that she has harbored a heterozygous c.787C>T (p.Q263*) variant of the ERF gene, which was not found in either parent. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+PS2+PM2_Supporting). In total 63 relevant cases were retrieved from the database, and a total of 64 individuals were analyzed by genetic testing. Most of the cases were sporadic and males. Multiple cranial sutures (including at least two of the sagittal suture, coronal suture, lambdoid suture, and frontal suture) were involved in 45.45% of the cases, and those with sagittal suture closure only have accounted for 20.00%. The main clinical manifestations have included hypertelorism, exophthalmos, development delay, malar dysplasia, etc. Chiari type 1 malformation may present in some patients. Variants of the ERF gene have mainly included splicing and deletional variants, and there was a strong genetic heterogeneity among the infants and their pedigrees. CONCLUSION The c.787C>T (p.Q263*) variant of the ERF gene probably underlay the craniosynostosis of this infant. Above finding has enriched the phenotype ~ genotype spectrum of the ERF gene.
Female ; Humans ; Cranial Sutures/surgery* ; Craniosynostoses/genetics* ; Genetic Testing ; Mutation ; Repressor Proteins/genetics* ; Infant

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree affected with van der Woude syndrome (VWS). METHODS: A proband who had visited the Drum Tower Hospital Affiliated to Nanjing University Medical School in May 2020 for "two previous pregnancies with cleft lip and palate" was selected as the study subject. Trio-whole exome sequencing (trio-WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of her pedigree members (8 individuals from four generations) and bioinformatic analysis. Chromosomal microarray analysis (CMA) was used to rule out copy number variations in the fetuses. RESULTS: Trio-WES revealed that the proband and her father had both harbored a heterozygous c.742G>T (p.G248C) missense variant of the IRF6 gene, for which her mother was of the wild type. The variant was located in a region with important functions and has not been reported previously. Prediction with several software suggested that it is likely to have a significant impact on the protein structure/function and is highly correlated with the specific phenotypes in this pedigree. Sanger sequencing confirmed co-segregation of the genotypes and phenotypes in the pedigree. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was rated as likely pathogenic (PM1+PM2_Supporting+PP1+PP3+PP4). Based on the above results, pre-implantation genetic diagnosis was carried out for the proband, which has led to birth of a healthy offspring with normal results for both site testing and CMA. CONCLUSION The IRF6: c.742G>T (p.G248C) heterozygous variant probably underlay the VWS in this pedigree. Above finding has also enabled reproductive guidance for the proband.
Humans ; Female ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Pedigree ; DNA Copy Number Variations ; East Asian People ; Interferon Regulatory Factors/genetics* ; Mutation

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). METHODS: A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. RESULTS: The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting). CONCLUSION The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.
Child ; Male ; Humans ; Infant ; Developmental Disabilities/genetics* ; Craniofacial Abnormalities/genetics* ; Seizures/genetics* ; Intellectual Disability/genetics* ; Problem Behavior ; Mutation

Humans ; Goldenhar Syndrome ; Phenotype ; Mutation ; DNA-Binding Proteins/genetics* ; Protein Tyrosine Phosphatases/genetics* ; Peptide Elongation Factors/genetics* ; Ribonucleoprotein, U5 Small Nuclear/genetics*

Objective:To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. Methods:From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography（PSG） and airway CT examination were performed before and 3 months after the surgery. Results:Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Conclusion:Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.
Humans ; Infant, Newborn ; Infant ; Micrognathism/surgery* ; Laryngomalacia/surgery* ; Treatment Outcome ; Mandible/surgery* ; Airway Obstruction/surgery* ; Intubation, Intratracheal ; Laryngeal Diseases ; Osteogenesis, Distraction ; Oxygen ; Retrospective Studies