Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Kartagener syndrome with obstructive azoospermia (KS-OAS). METHODS: We collected the clinical data and results of examinations of a male infertility patient treated in the Women and Children's Hospital Affiliated to Xiamen University. We analyzed the genetic etiology of the patient by high-throughput sequencing and bioinformatics, verified the pathogenic variants of CCDC114 by Sanger sequencing of the family members, and determined the protein expression of CCDC114 in normal subjects by immunohistochemistry and immunofluorescence staining. RESULTS: The patient was confirmed with KS-OAS, and found with biallelic variation of CCDC114 (c.71-2A>C, c.816_817insGCAG) by sequencing, which were inherited from father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the variants were pathogenic. Two offspring were obtained by intracytoplasmic sperm injection (ICSI). CONCLUSION The above findings have broadened the variation spectrum of the CCDC114, and provided some new ideas for genetic and assisted reproduction counseling for patients with Kartagener syndrome. The variation of CCDC114 does not affect the pregnancy outcome of ICSI.
Adult ; Humans ; Male ; Azoospermia/genetics* ; Kartagener Syndrome/complications* ; Mutation ; Sperm Injections, Intracytoplasmic

Objective:To investigate the outcomes of endoscopic balloon dilation laryngoplasty （EBDL） in managing acquired subglottic stenosis in children. Methods:A retrospective analysis of clinical data from patients who underwent endoscopic balloon dilation for secondary subglottic stenosis between January 2017 and January 2024 at Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai. The study included 10 children （6 males, 4 females） aged between 13 days and 3 years at the time of their first procedure, with an average age of 7 months. Subglottic stenosis was graded according to the Myer-Cotton classification, with two cases classified as grade Ⅱ and eight cases as grade Ⅲ. All patients had a history of tracheal intubation, including seven for rescue purposes and three for operations. Eight cases were complicated by other conditions: two with atrial septal defect, patent ductus arteriosus, and patent foramen ovale; two with patent foramen ovale only; one with atrial septal defect and extreme deafness in the left ear; one with a brain tumor and hydrocephalus; one with a traumatic diaphragmatic hernia and hepatic rupture; and one case complicated by type Ⅰ laryngeal cleft. Prior to surgery, all children required respiratory support-seven needed high-flow oxygen while three required CPAP. Results:All ten cases underwent endoscopic balloon dilation under spontaneous respiration and general anesthesia, totaling fourteen dilations （an average of 1.4 dilations per person） without any complications. Post-surgery air permeability tests showed that eight cases had grade Ⅰ stenosis while two had grade Ⅱ stenosis. The follow-up period ranged from six months to six years （average duration: 46 months）. Following treatment, all patients no longer required respiratory support or experienced significant mobility limitations. Conclusion:Endoscopic balloon dilation under general anesthesia is deemed safe and effective in treating secondary subglottic stenosis. Early diagnosis coupled with prompt intervention can help avoid tracheotomy procedures altogether. Standard tracheoscopy combined with breathability testing represents a crucial approach to assess normal airway diameter and effectively reduce or prevent secondary subglottic stenosis following re-intubation.
Humans ; Laryngostenosis/surgery* ; Male ; Female ; Retrospective Studies ; Laryngoplasty/methods* ; Child, Preschool ; Infant ; Dilatation/methods* ; Laryngoscopy/methods* ; Treatment Outcome ; Endoscopy

Objective:Explore the clinical diagnosis and treatment strategies of recurrent multiple chondritis in children with airway involvement as the main cause. Methods:From June 2021 to May 2023, five children with relapsing polychondritis were admitted to our department, all of whom met the Damiani criteria. Tracheotomy was performed in all five patients. Endoscopy indicated subglottic stenosis, with one case classified as grade Ⅲ and four cases as grade Ⅳ according to the Myer-Cotton classification. Enhanced CT scans of the head and neck showed fixed lumen narrowing and stenosis, including thickening of the soft tissue in the laryngeal cavity and partial absorption of the laryngotracheal cartilage anterior wall. In one patient, tracheal wall thickening and deformation with stenosis and calcification involved the posterior tracheal wall. One patient underwent "laryngeal tracheal reconstruction with hyoid graft, T-tube implantation, and bioabsorbable corticosteroid-eluting stent implantation", while three patients underwent "balloon dilatation, T-tube implantation, and bioabsorbable corticosteroid-eluting stent implantation" . Follow-up was performed every two months after the initial surgery, and three bioabsorbable corticosteroid-eluting stents were placed on the upper left, upper right, and lower T-tube, respectively, during this time. The entire follow-up period was six months. Results:All the 5 cases were in the outpatient department, of which 1 case had been extubation, 3 cases were still in the outpatient follow-up, and the remaining 1 case was still being treated in the rheumatology and immunology department due to poor control of the primary disease. Conclusion:In relapsing polychondritis children with airway involvement, tracheotomy could be used to quickly improve the symptoms of dyspnea in the disease progression. In the stable stage of the disease, the surgical method of 'Balloon dilatation + T-tube implantation + Bioabsorbable corticosteroid-eluting stents implantation' was adopted to reduce the secondary injury caused by surgical trauma as much as possible and improve the survival and quality of life of the children.
Humans ; Polychondritis, Relapsing/surgery* ; Child ; Male ; Female ; Tracheotomy ; Laryngostenosis ; Child, Preschool ; Trachea/surgery* ; Adolescent ; Stents

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with Primary ciliary dyskinesia (PCD). METHODS: A child who presented at the ENT Department of Zhengzhou University Children's Hospital in March 2024 due to secretory otitis media, chronic sinusitis, adenoid hypertrophy, dextrocardia, and bronchiectasis was selected as study subject. Relevant clinical data were collected. Peripheral blood samples from the child and her family members were collected. Following DNA extraction, whole exome sequencing was carried out. Candidate variants were validated by Sanger sequencing, and the correlation between the variants and phenotype was analyzed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-K-135). RESULTS: The child and her elder siblings exhibited similar clinical manifestations including recurrent cough, secretory otitis media, chronic sinusitis, tracheobronchitis, and pneumonia. The child also presented with bronchiectasis and visceral situs inversus. Genetic testing results indicated that the child and her elder siblings had all harbored compound heterozygous variants of the DNAH11 gene, namely c.3000 1G>A and c.5775C>G (p.Tyr1925*), which were respectively inherited from their phenotypically normal parents. Both variants can affect mRNA splicing and protein translation integrity. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic. It was predicted that they may jointly lead to a functional defect in axonemal dynein, resulting in the phenotype of PCD, conforming to an autosomal recessive inheritance. CONCLUSION The compound heterozygous variants c.3000 1G>A and c.5775C>G (p.Tyr1925*) of the DNAH11 gene probably underlay the pathogenesis of PCD in this pedigree. The same variant in different individuals may lead to different clinical phenotypes, which has reflected significant heterogeneity in genetic background and clinical phenotype. Above findings have enriched the mutational spectrum of PCD gene and have important implications for the accurate diagnosis, treatment, prognosis, and genetic counseling.
Humans ; Pedigree ; Female ; Axonemal Dyneins/genetics* ; Male ; Child ; Asian People/genetics* ; Kartagener Syndrome/genetics* ; Mutation ; Phenotype ; China ; Adult ; East Asian People

Objective: A retrospective study of the demographic, clinical and diagnostic profile, intervention and outcomes of children with Congenital Pulmonary Airway Malformation (CPAM) in Philippine Children’s Medical Center (PCMC) from January 2011 to December 2021 was presented. Methodology: Medical charts of identified patients were reviewed. Data obtained included demographic profile, clinical history, diagnostic procedures, intervention, and outcomes. The findings were analyzed and correlated with the synthesized findings from relevant studies about CPAM. Results: Twenty-three cases (n=23) were included in the study. Most of the patients were diagnosed at 1 to 11 months of age, accounting for 43.48% while there is a minimal disparity in terms of gender distribution. Seventy-five percent of neonates presented with respiratory distress while recurrent pneumonia occurred more frequently beyond the neonatal period. Four patients at 17.39% had incidental findings of CPAM on prenatal ultrasound. All cases were confirmed using a Chest CT scan and only six patients at 26.09% had Chest X-ray results consistent with CPAM. Eight cases were confirmed using biopsy wherein results were mainly Type I seen in 87.5% of cases. Lobectomy is the procedure of choice with 92.86% success rate. Overall, patients who underwent surgical intervention had a low complication rate at 6.25%. Conclusion CPAM is most common in patients aged 1 to 11 months and has no gender predilection. Neonates often present with respiratory distress while recurrent pneumonia is the most common clinical manifestation beyond neonatal period. CPAM can be detected using ultrasound prenatally and CT scan can confirm CPAM postnatally. Surgical intervention particularly lobectomy is the preferred option over conservative management which showed a favorable outcome. CPAM has an overall good prognosis. Findings of this research may guide clinicians in the diagnosis and management of CPAM in the Philippines.
Cystic Adenomatoid Malformation of Lung, Congenital

This article reports a case of congenital choanal atresia with additional nostril and nasal deformities admitted to Henan Children's Hospital. A 43-day-old female patient was admitted to the hospital because of wheezing with mouth opening breathing and restricted feeding after birth'. The patient was diagnosis as bilateral congenital posterior nostril membranous atresia, congenital extra nostril nasal deformity and nasal stenosis by fiberoptic nasopharyngoscopy, CT, gene detection, and physical examination results. Under general anesthesia, endoscopic bilateral posterior nostril plasty and left anterior nostril plasty were performed. The child recovered well after operation.
Humans ; Choanal Atresia/surgery* ; Female ; Nasal Cavity/abnormalities* ; Infant ; Nose/surgery* ; Endoscopy/methods*

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Kartagener syndrome (KTS). METHODS: Trio-whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. Changes in protein structure due to missense variants were simulated and analyzed, and the Human Splicing Finder 3.0 (HSF 3.0) online platform was used to predict the effect of the variant of the non-coding region. RESULTS: The child had featured bronchiectasis, sinusitis and visceral inversion. Genetic testing revealed that he has harbored compound heterozygous variants of the DNAH5 gene, namely c.5174T>C and c.7610-3T>G. Sanger sequencing confirmed the existence of the variants. The variants were not found in the dbSNP, 1000 Genomes, ExAC, ClinVar and HGMD databases. Protein structural analysis suggested that the c.5174T>C (p.Leu1725Pro) variant may affect the stability of local structure and its biological activity. The results of HSF 3.0 analysis suggested that the c.7610-3T>G variant has probably destroyed a splicing receptor to affect the transcription process. CONCLUSION The compound heterozygous variants of the DNAH5 gene probably underlay the pathogenesis in the child. Above finding may facilitate the understanding of the clinical characteristics and genetic basis of KTS, and further expand the spectrum of DNAH5 gene variants.
Male ; Humans ; Child ; Mutation ; Kartagener Syndrome/genetics* ; Genetic Testing ; Mutation, Missense ; Exome Sequencing ; Axonemal Dyneins/genetics*

OBJECTIVES: To evaluate the clinical effectiveness of integrated management during the perinatal period for fetuses diagnosed with total anomalous pulmonary venous connection (TAPVC) by prenatal echocardiography. METHODS: Clinical data of 64 cases of TAPVC fetuses diagnosed by prenatal echocardiography and managed with integrated perinatal care in Qingdao Women and Children's Hospital from January 2017 to December 2021 were retrospectively analyzed. Integrated perinatal care included multidisciplinary collaboration among obstetrics, fetal medicine, ultrasound, pediatric cardiology, pediatric anesthesia, and neonatology. RESULTS: Among the 64 TAPVC fetuses, there were 29 cases of supracardiac type, 27 cases of intracardiac type, 2 cases of infracardiac type, and 6 cases of mixed type. Chromosomal analysis was performed in 42 cases, and no obvious abnormalities were found. Among the 64 TAPVC fetuses, 37 were induced labor, and 27 were followed up until term birth. Among the 27 TAPVC cases, 2 cases accepted palliative care, 2 cases were referred to another hospital for treatment and lost to follow-up, while the remaining 23 cases underwent primary repair surgery. One case died within 6 months after the operation due to low cardiac output syndrome, while the other 22 cases were followed up for (2.1±0.3) years with good outcomes (2 cases underwent a second surgery within 1 year after the first operation due to anastomotic stenosis or pulmonary vein stenosis). CONCLUSIONS TAPVC fetuses can achieve good outcomes with integrated management during the perinatal period.
Female ; Humans ; Pregnancy ; Echocardiography ; Heart Defects, Congenital/surgery* ; Pulmonary Veins/surgery* ; Retrospective Studies ; Scimitar Syndrome/surgery* ; Infant, Newborn

Infants with laryngotracheal anomalies are clinically manifested as stridor or noisy breathing, choking, hoarseness, feeding difficulties, and cyanotic spells, followed by developmental and growth retardation and other health issues; in severe cases, patients may present with severe dyspnea, which is associated with high mortality. A timely diagnosis as well as appropriate strategy for laryngotracheal anomalies is still challenging for pediatric otolaryngologists. This consensus statement, evolved from expert opinion by the members of the Pediatric Otorhinolaryngology Professional Committee of the Pediatrician Branch of the Chinese Medical Doctor Association, provides comprehensive recommendations and standardized guidance for otolaryngologists who manage infants and young children with laryngotracheal anomalies in evaluation and treatment based on symptomatology, physical and laboratory examinations.
Humans ; Child ; Infant ; Child, Preschool ; Laryngostenosis/surgery* ; Airway Obstruction/complications* ; Hoarseness/complications* ; Consensus ; Respiratory Sounds