Objective:To explore the feasibility of endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the external fistula incision approach. Methods:A retrospective analysis was conducted on 20 children with congenital first and second branchial cleft malformations who were admitted to the Department of Otolaryngology Head and Neck Surgery of Hu'nan Children's Hospital from January 2020 to January 2024 and whose families voluntarily consented to endoscopic surgery. Clinical data were collected. There were 12 males and 8 females, aged from 10 months to 12 years. The surgical methods and experiences of endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the external fistula incision approach were summarized. Results:All 20 children underwent endoscopic-assisted resection of congenital first and second branchial cleft malformations via the external fistula incision approach. For children with second branchial cleft malformations whose internal fistula openings were located on the pharyngeal arch mucosa or palatine tonsils, the tonsils were preserved, the internal fistula openings were ligated at a high position, the fistula tubes were removed, and the residual ends were cauterized with bipolar electrocoagulation to destroy the residual fistula epithelial cells. There were no obvious complications after the operation. During the 12-month follow-up, no recurrence of the fistula tubeswas observed, and the recovery was good. Conclusion:Congenital first and second branchial cleft fistulas in children are rare, and surgical resection is the preferred treatment method. The endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the fistula incision approach offers a clear surgical field, an ideal cosmetic effect, and a satisfactory curative effect.
Humans ; Female ; Male ; Branchial Region/surgery* ; Retrospective Studies ; Child ; Infant ; Child, Preschool ; Endoscopy/methods* ; Fistula/surgery* ; Craniofacial Abnormalities/surgery* ; Treatment Outcome ; Pharyngeal Diseases

Global developmental delay (GDD) and intellectual disability (ID) refer to deficits in cognitive and adaptive functioning that arise during the developmental period. GDD/ID is often accompanied by complex developmental abnormalities, with congenital craniofacial malformations being among the most common, such as craniosynostosis, cleft lip and palate, and congenital tooth agenesis. However, the underlying mechanisms of GDD/ID associated with congenital craniofacial malformations remain unclear. With the increasing number of reported genetic syndromes, genetic factors are emerging as key contributors to the concurrent abnormalities in brain and craniofacial development. Studies have identified Wnt, SHH, FGF, and BMP as classical regulatory molecules in craniofacial development, and their roles have also been closely linked to various stages of brain development. This review focuses on the regulatory roles of Wnt, SHH, FGF, and BMP signaling pathways in brain and craniofacial development, as well as the pathogenic mechanisms underlying their association with GDD/ID and craniofacial malformations. The aim is to provide new insights into the etiology of GDD/ID combined with congenital craniofacial malformations.
Humans ; Craniofacial Abnormalities/complications* ; Signal Transduction ; Developmental Disabilities/metabolism* ; Intellectual Disability/complications* ; Animals ; Hedgehog Proteins/genetics* ; Fibroblast Growth Factors/genetics*

OBJECTIVE: To block the transmission of Cranio-facial-nasal syndrome (CFNS) caused by a large deletion of the EFNB1 gene through preimplantation genetic testing for monogenic disorders (PGT-M). METHODS: A patient with craniofacial deformities and his parents who had visited Shiyan People's Hospital in June 2020 were selected as the study subjects. The child underwent whole exome sequencing (WES) and qPCR validation. After genetic counseling, PGT-M was chosen for the reproductive blockage. This study was approved by the Ethics Committee of the Hospital (Ethics No.: sysrmyy-087). RESULTS: The child was diagnosed with CFNS due to a heterozygous deletion of exons 1-5 of the EFNB1 gene through WES and qPCR, which showed a X-linked dominant inheritance. The mother underwent ovarian stimulation with a modified PPOS protocol, which has yielded 11 oocytes. After ICSI fertilization, 4 blastocysts were formed, and MALBAC whole genome amplification was performed on the trophoblast biopsy cells, and SNP haplotypes of the family members and embryos were analyzed to indirectly determine the presence of maternal pathogenic haplotypes. Chromosomal copy number variation analysis was conducted through next-generation sequencing to screen for euploid embryos, resulting in the identification of two euploid embryos that did not carry the mutation of the EFNB1 gene. The first transfer was unsuccessful, but after adjusting the transfer timing through endometrial receptivity assessment (ERA), clinical pregnancy was achieved. Prenatal diagnosis at 19 weeks excluded the EFNB1 gene exons 1-5 deletion in the fetus. A healthy girl was delivered by Cesarean section at 38⁺⁶ weeks, and Q-PCR confirmed she has no aforementioned EFNB1 gene deletion. CONCLUSION This study has successfully blocked the transmission of CFNS caused by a large deletion of the EFNB1 gene (exons 1-5) using a PGT-M strategy, which may provide reference for the intervention of similar genomic variations that cannot be directly detected.
Humans ; Female ; Male ; Craniofacial Abnormalities/diagnosis* ; Ephrin-B1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Pedigree ; Asian People/genetics* ; Craniosynostoses/genetics* ; Pregnancy ; Gene Deletion ; Sequence Deletion ; Genetic Testing/methods* ; Adult ; East Asian People

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

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97^th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.
Male ; Humans ; Child ; Intellectual Disability/genetics* ; Developmental Disabilities/genetics* ; Retrospective Studies ; Seizures/genetics* ; Craniofacial Abnormalities/genetics* ; Histone Deacetylases/genetics*

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

Objective:To compare the clinical effect of surgical treatment of congenital preauricular fistulas in children during the local infection period and static inflammatory period. Methods:Forty children with congenital preauricular fistula infection treated in our hospital from January 2020 to December 2022 were selected as the experimental group, and 39 children with congenital preauricular fistula inflammation at static period were selected as the control group. The fistula of the two groups of children aged between 1-14 years old was located in front of the foot of the ear wheel or the foot of the ear wheel, and all were unilateral fistulas. The postoperative follow-up was 6 months to 2 years, and the efficacy of the two groups was compared. Results:There was no significant difference in the healing rate of stage Ⅰ and stage Ⅱ between the two groups（P>0.05）. There was no significant difference in fistula recurrence rate and satisfaction with the preauricular scar between the two groups after treatment（P>0.05）. There was no significant difference in postoperative hospital stay between the experimental group and the control group（P>0.05）. Conclusion:The effect of surgical treatment of congenital preauricular fistula in the infected period is similar to that of surgical treatment in the static period of inflammation, and it can reduce the pain of dressing change under local anesthesia in children, avoid the second operation in children, and reduce the economic cost. This treatment method is worthy of clinical promotion. Appropriate incision and resection method were designed according to the fistula and infection sites.
Humans ; Child ; Infant ; Child, Preschool ; Adolescent ; Fistula/surgery* ; Inflammation ; Craniofacial Abnormalities/surgery* ; Cicatrix ; Treatment Outcome

Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.
Abnormalities, Multiple ; Child ; Child, Preschool ; Craniofacial Abnormalities ; Female ; Growth Disorders/genetics* ; Histone-Lysine N-Methyltransferase ; Humans ; Hypertrichosis/genetics* ; Infant ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein ; Pregnancy ; Syndrome

OBJECTIVE: To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID). METHODS: Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA). RESULTS: Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance. CONCLUSION Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities/genetics* ; DNA Copy Number Variations ; Developmental Disabilities/genetics* ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics*

OBJECTIVE: To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome. METHODS: Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Copy number variations (CNV) were detected by CNV-seq and validated by real-time PCR. RESULTS: Proband 1 was found to carry a de novo heterogeneous variant (c.823+1G>T) of the EHMT1 gene, which may affect its expression. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS2+PM2). Proband 2 was found to carry a de novo missense variant c.439C>G (p.L147V) of the EHMT1 gene, which was predicted to be likely pathogenic (PS2+PM1+PM2+PP3). Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq. The deletion has encompassed the whole of the EHMT1 gene. Real-time PCR has detected no CNV of this region in her parents. CONCLUSION Variants of the EHMT1 gene probably underlay the disease in these patients. Genetic testing has provided a basis for their clinical diagnosis.
Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities ; DNA Copy Number Variations ; Female ; Genetic Testing ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics* ; Mutation