We report the case of a 33-week-old female fetus born with craniorachischisis to a gravida 5, para 4 (3104) mother with no previous history of conceiving a child with a neural tube defect. Craniorachischisis is characterized by anencephaly and an open defect extending from the brain to the spine and is the most severe and fatal type of neural tube defect. Although the cause of neural tube defects is hypothesized to be multifactorial and is usually sporadic, the risk is increased in neonates born to mothers with a family history or a previous pregnancy with neural tube defect, both of which are not present in the index case. This case is unique in that only during the fifth pregnancy did the couple conceive a child with a neural tube defect, emphasizing that folic acid supplementation, the sole preventive measure proven to decrease the risk of neural tube defects, remains to be important in the periconceptual period for all women of childbearing age.
Autopsy ; Congenital Abnormalities ; Neural Tube Defects ; Neural Tube Defects

This paper focuses on the diagnosis and treatment of disorders of laryngeal airway in children, including congenital anomalies, infection, and tumor of the larynx to provide a new technology for managing these diseases. Based on the characteristic of them, the pediatric upper airway is dedicated to the clinical evaluation of airway obstruction and the assessment of the compromised pediatric airway, including clinical evaluation of symptoms, diagnostic endoscopy, and imaging examination. Information on endoscopic techniques used for dealing with different degrees of pediatric airway comprised is provided, also this techniques could diagnose what kinds of airway disorder. For example, determining the a particular laryngeal cleft at the initial otolaryngology encounter, flexible laryngoscopy should be performed. In order to define the extent of any identified cleft, the rigid bronchoscopy should be completed to evaluate for classification of laryngeal cleft including typeⅠ, Ⅱ, Ⅲa, Ⅲb, Ⅳa, Ⅳb under general anesthesia. The decision to pursue any therapy for the disorders of laryngeal airway in children should be based on the severity of the patient's symptoms, endoscopic and imaging examination. There are two medical treatments including nonsurgical therapy and surgical therapy. For example the laryngeal cleft, approximately half of type 1 and select type 2 patients can be managed entirely with nonsurgical therapy. Medical management is multifaceted. Under recommendations from the feeding team, a modified diet with thickened feeds and possibly altered feeding position should be initiated. Endoscopic surgical repair is the current gold standard for definitive repair of type 1, the majority of type 2, and selected type 3 clefts. Finally, information on new techniques used into the future for dealing with the diagnosis and treatment of disorders of laryngeal airway in children in this paper.
Child ; Humans ; Infant ; Larynx/surgery* ; Laryngoscopy ; Endoscopy ; Bronchoscopy ; Congenital Abnormalities/surgery*

Objective:To analyze the efficacy of endoscopic surgical repair in the treatment of type Ⅲ laryngeal clefts and to explore the feasibility of the treatment for type Ⅲ laryngeal clefts. Methods:The clinical data of 6 children with type Ⅲ laryngeal clefts who underwent endoscopic surgical repair in our department from June 2018 to January 2023 were analyzed retrospectively. The operation was performed under combined intravenous and general anesthesia,preserving the spontaneous breathing of the children. With the assistance of 4 mm/0° endoscope, radiofrequency knife or laryngeal scissors were used to make fresh wounds along the edge of laryngeal clefts,and cotton pads infiltrated with adrenaline （1:10 000） were used to compress the wound. 6-0 PDP suture was used to suture 3-6 stitches according to the extent of laryngeal clefts. Modified barium swallowing test （MBS） was performed 3 months after operation. Results:All the children were successfully treated with endoscopic surgical repair. After surgery, 2 cases were transferred to pediatric intensive care unit （ICU） for 7 days of monitoring, and the rest were transferred back to the general ward. There were no postoperative complications. The symptoms of dysphagia, laryngitis and recurrent pneumonia were improved in all children. According to the follow-up results of postoperative MBS,no aspiration was found in all children, and 2 children had intermittent cough when drinking large amounts of water. During the follow-up, there were 2 cases of recurrence, and the cracks were completely repaired after the second endoscopic surgical repair treatment,and no recurrence has been observed so far. Conclusion:Endoscopic surgical repair can be applied to some children with type Ⅲ laryngeal clefts with less intraoperative bleeding and fewer operative complications. It can significantly improve the symptoms such as swallowing dysfunction and recurrent pneumonia. It is a safe and effective surgical treatment.
Child ; Humans ; Laryngoscopy/methods* ; Laryngoscopes ; Retrospective Studies ; Larynx/surgery* ; Pneumonia ; Congenital Abnormalities/surgery*

At present, there is no unified gold standard for the treatment of laryngeal clefts. Type Ⅰ laryngeal clefts with mild symptoms can be treated conservatively, such as thick diet feeding and using proton pump inhibitor to control reflux, while Ⅱ-Ⅳ laryngeal clefts mostly requires surgical intervention.There are many different surgical methods for the treatment of laryngeal clefts, including injection laryngoplasty, endoscopic surgical repair of laryngeal clefts and open laryngoplasty through anterior cervical approach. How to choose a more suitable surgical plan for children is a problem worth discussing. This article will review the literature on the surgical treatment of laryngeal clefts both domestically and internationally, and summarize the current situation and challenges of surgical treatment of laryngeal clefts.
Child ; Humans ; Congenital Abnormalities/surgery* ; Endoscopy ; Laryngoplasty/methods* ; Laryngoscopy/methods* ; Larynx/surgery*

A full-term female infant was admitted at 5 hours after birth due to heart malformations found during the fetal period and cyanosis once after birth. Mmultiple malformations of eyes, face, limbs, and heart were noted. The whole-exome sequencing revealed a pathogenic heterozygous mutation, c.2428C>T(p.Arg810^*), in the BCOR gene. The infant was then diagnosed with oculo-facio-cardio-dental syndrome. He received assisted ventilation to improve oxygenation and nutritional support during hospitalization. Right ventricular double outlet correction was performed 1 month after birth. Ocular lesions were followed up and scheduled for elective surgery. The possibility of oculo-facio-cardio-dental syndrome should be considered for neonates with multiple malformations of eyes, face, and heart, and genetic testing should be performed as early as possible to confirm the diagnosis; meanwhile, active ophthalmic and cardiovascular symptomatic treatment should be given to improve the prognosis.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Abnormalities, Multiple/therapy* ; Cataract/genetics* ; Cyanosis ; Proto-Oncogene Proteins ; Repressor Proteins/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE: To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS). METHODS: A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. RESULTS: Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to be de novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome. CONCLUSION The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.
Female ; Humans ; DNA Copy Number Variations ; Fetal Diseases ; Fetus/abnormalities* ; Heart Defects, Congenital/genetics* ; Mutation ; Transcription Factors/genetics*

OBJECTIVES: Congenital birth defects are the main source of disease burden among children under 5 years old in China. This study aims to compare the trends in disease burden of different congenital birth defects among Chinese children under 5 years old from 1990 to 2019, and to provide a scientific basis for strengthening the comprehensive prevention and control of birth defects. METHODS: Based on data from the Global Burden Disease (GBD) in 2019, the incidence mortality rate, and disability-adjusted life years (DALYs) rate of congenital birth defects among Chinese children under 5 years old from 1990 to 2019 were selected as evaluation indicators. The Joinpoint regression model was used to analyze the trends in disease burden of different types with congenital birth defects over three decades. The study also compared the differences in disease burden of congenital birth defects among children under 5 years old by gender. RESULTS: Compared to 1990, the DALYs rates of congenital heart anomalies (1 931.91/100 000), digestive congenital anomalies (364.63/100 000), neural tube defects (277.20/100 000), congenital musculoskeletal and limb anomalies (133.33/100 000), and Down syndrome (128.22/100 000) in children under 5 years old in China in 2019 were decreased 70.78%, 71.61%, 86.21%, 36.84% and 73.65%, respectively. From 1990 to 2019, the mortality rates and DALYs rates of different congenital birth defects showed an overall downward trend, but the incidence of digestive congenital anomalies and Down syndrome showed an upward trend after 2005 and 2001, respectively. Except for congenital musculoskeletal and limb anomalies, incidence of the remaining categories of birth defects were higher in boys than that in girls. CONCLUSIONS The disease burden of congenital birth defects in children under 5 years old in China is decreased substantially from 1990 to 2019, but the burden of congenital heart anomalies is still serious and the incidence of some birth defect diseases is on the rise, and it is still crucial to strengthen the prevention and treatment for birth defects in children and propose targeted measures according to their gender characteristics.
Child, Preschool ; Female ; Humans ; Male ; China/epidemiology* ; Cost of Illness ; Down Syndrome/epidemiology* ; East Asian People ; Congenital Abnormalities/epidemiology*

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 explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Hand Deformities, Congenital ; Humans ; Intellectual Disability ; Micrognathism ; Neck/abnormalities* ; Pedigree ; Transcription Factors/genetics*

OBJECTIVE: To explore the genetic basis for two unrelated patients with global developmental delay and coarse facial features. METHODS: Clinical data and family history of the two pedigrees were collected. Whole exome sequencing and Sanger sequencing were carried out to detect potential variants. RESULTS: The two patients have presented with global developmental delay, coarse facies, muscular hypotonia, congenital heart disease, and pectus excavatum, and were found to harbor two de novo loss-of-function variants of the ARID1B gene, namely c.3586delC (p.Gln1196Serfs*15) and c.4954_4957delACGT (p.Thr1652Glyfs*31). Both variants were unreported previously. CONCLUSION The nonsense variants of the ARID1B gene probably underlay the etiology in these patients. Above finding has enriched the genotypic and phenotypic spectrum of the disease and provided a basis for prenatal diagnosis.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Facies ; Hand Deformities, Congenital/genetics* ; Humans ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Neck/abnormalities* ; Transcription Factors/genetics*