Translational pediatrics最新文献

{"title":"<i>POGZ</i> variants in neurodevelopmental delay: a case series on phenotype-genotype correlation.","authors":"Hongmei Huang, Chenlu Yang, Jiangqiang Ma, Haitian Li, Shijie Li","doi":"10.21037/tp-2025-477","DOIUrl":"https://doi.org/10.21037/tp-2025-477","url":null,"abstract":"<p><strong>Background: </strong>POGO transposable element with ZNF domain (<i>POGZ</i>) gene is one of the most recurrently mutated genes in patients with neurodevelopmental delay (NDD). The number of reported <i>POGZ</i> variants continues to increase, and phenotypic reporting likely varies between different series.</p><p><strong>Case description: </strong>Five children with heterozygous <i>POGZ</i> variants, including two protein truncating variants (PTVs) and three missense variants, were found in our NDD patients with or without autism. A total of 201 patients carrying 158 different variants in the <i>POGZ</i> gene were reviewed to investigate the correlations between phenotypes and genotypes of these <i>POGZ</i> variants.</p><p><strong>Conclusions: </strong><i>POGZ</i> gene PTVs were associated with a wider range of phenotypes and a higher frequency of some clinical features than missense variants. In addition, almost half of the PTVs located in the last two exons had more severe phenotypes than those in other exons. Missense variants were associated with fewer and milder phenotypes, but with a higher frequency of the autism phenotype. <i>POGZ</i> PTVs located in the last two exons, were linked to higher incidence rates of severe developmental delay (DD) and speech delay symptoms. Our study delineates the phenotypic spectrum associated with protein-truncating variants (PTVs) and missense variants in the <i>POGZ</i> gene, revealing a correlation with variable disease severity. These findings highlight the importance of genotype-driven strategies in clinical practice.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"81"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microcephaly, seizures and developmental delay caused by two novel mutations in the <i>PNKP</i> gene: a case report.","authors":"Min Liu, Dan-Ping Huang, Man-Li Wang, Dong-Jing Zhao, Jun Feng, Feng-Ming Zhu, Zhen-Long Zhang, Xu-Qin Chen","doi":"10.21037/tp-2025-1-820","DOIUrl":"https://doi.org/10.21037/tp-2025-1-820","url":null,"abstract":"<p><strong>Background: </strong>Microcephaly, seizures and developmental delay, known as MCSZ, is an uncommon autosomal recessive neurodevelopmental disorder linked to a bifunctional enzyme named polynucleotide-kinase-3'-phosphatase (<i>PNKP</i>). Prompt identification and management of the disorder are crucial, as delayed diagnosis or intervention may lead to severe complications or mortality.</p><p><strong>Case description: </strong>We describe a patient with small anterior fontanelle and head circumference, refractory epilepsy and global developmental delay. He was a baby conceived via in vitro fertilization (IVF). Microcephaly and oligohydramnios were detected at 32 weeks. At 4 months, the patient had recurrent convulsions without fever, presenting with tonic-clonic seizures. He was treated with four anti-seizure medications (ASMs), but did not achieve satisfactory control. At the age of 5 years old, he had not learned to speak and was unable to stand unaided. The patient harbored two novel mutations, c. 1299-1G>A and c.1283_1287dup (p.S430Pfs*39), in the <i>PNKP</i> gene. We confirmed, through RNA-seq, that c. 1299-1G>A results in exon 15 skipping and intron 14 retention. Both variants led to a truncated protein and may affect protein stability and enzyme activity.</p><p><strong>Conclusions: </strong>This is the third report of MCSZ in a non-consanguineous Chinese mainland family. Our results offer additional evidence for clinical variability associated with disorders stemming from mutations in the <i>PNKP</i> gene, which complicates disease diagnosis. This underscores the significance of genetic testing to identify the underlying causes of these conditions. Furthermore, these findings expand the mutation spectrum of the <i>PNKP</i> gene and establish a solid foundation for both clinical and prenatal diagnoses within this family.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"87"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence delirium prevention through electroencephalogram-guided anesthesia: a new standard for pediatric care?","authors":"Luiza Mendes Costa Lino, Ricardo Vieira Carlos, Vinícius Caldeira Quintão","doi":"10.21037/tp-2025-1-888","DOIUrl":"https://doi.org/10.21037/tp-2025-1-888","url":null,"abstract":"","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"66"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel large deletion mutation in the <i>AVPR2</i> gene responsible for hereditary nephrogenic diabetes insipidus in an infant: a case report.","authors":"Yuan Huang, Lingling Liu, Di Ma, Yuanyuan Lu, Feng Fang, Xinglou Liu","doi":"10.21037/tp-2025-1-924","DOIUrl":"https://doi.org/10.21037/tp-2025-1-924","url":null,"abstract":"<p><strong>Background: </strong>Hereditary nephrogenic diabetes insipidus (HNDI) type1 is a rare genetic disorder that results from mutations in the <i>AVPR2</i> gene, which encodes the arginine vasopressin receptor 2. The primary clinical manifestations of this disorder encompass polydipsia, polyuria and urine with low specific gravity. At present, there is no curative treatment, and the principal treatment goal is to manage symptoms in order to prevent complications such as dehydration, brain injury, and hydroureteronephrosis.</p><p><strong>Case description: </strong>This case report presents a 7-month-old boy who presented with persistent low-grade fever that could not be explained by common infections, rheumatological and immunological diseases and other etiologies, resulting in difficulties in diagnosis and poor treatment outcomes. However, through a comprehensive review of the medical history and meticulous screening of laboratory tests, it was discovered that the child exhibited polyuria and low-specific-gravity urine, accompanied by a family history indicating polydipsia and polyuria. Following fluid replacement and oral administration of hydrochlorothiazide, the fever abated. Whole-exome sequencing disclosed a copy-number deletion of approximately 2.046 kb at Xq28, which entailed the deletion mutation of exons 3-4 of the haploinsufficient gene <i>AVPR2</i>. This was expected to lead to nonsense-mediated decay, and finally, the diagnosis of HNDI type1 was confirmed.</p><p><strong>Conclusions: </strong>The primary clinical manifestation of this case is fever, which underscores the atypical symptoms of nephrogenic diabetes insipidus during infancy. It also emphasizes the necessity of considering the potential for dehydration fever caused by diabetes insipidus when diagnosing fever of unknown origin. Furthermore, in this case, the copy number variation of the <i>AVPR2</i> gene was successfully identified via whole-exome sequencing technology. A novel large-fragment deletion mutation was discovered, which broadens the mutation spectrum of the <i>AVPR2</i> gene and substantially enhances the diagnostic accuracy.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"88"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic spectrum and risk factor analysis for drug-resistant of early-onset epilepsy.","authors":"Mingyu Han, Xinmin Ju, Xiangxiang Chen, Peipei Zou, Dingwen Wu, Wei Shi, Meihong Gu, Tianming Yuan","doi":"10.21037/tp-2025-aw-826","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-826","url":null,"abstract":"<p><strong>Background: </strong>Early-onset epilepsy, particularly with neonatal onset, frequently has a genetic basis, though predictors of drug resistance remain poorly characterized. This study investigates clinical and genetic risk factors for drug-resistant epilepsy (DRE) in infants with unexplained seizures.</p><p><strong>Methods: </strong>In this retrospective cohort study, 75 infants admitted to a tertiary neonatal center (2018-2025) underwent next-generation sequencing (NGS) and were stratified into DRE (n=35) and non-refractory epilepsy (n=40) groups based on seizure control. Comparative analyses evaluated both clinical and genetic domains. The clinical evaluation covered dysmorphic features, motor tone, feeding, neuroelectrophysiology, neuroimaging, antiseizure medication (ASM) use, and neurodevelopment. Genetic profiles were also compared across the cohorts.</p><p><strong>Results: </strong>DRE patients showed significantly higher rates of abnormal muscle tone (68.6% <i>vs.</i> 25.0%, P<0.001), feeding difficulties (37.1% <i>vs.</i> 12.5%, P=0.01), and epileptiform discharges on electroencephalogram (EEG) (82.9% <i>vs.</i> 30.0%, P<0.001). Developmental delay was more prevalent in DRE cases (77.4% <i>vs.</i> 25.7%, P<0.001). Definitive genetic diagnosis was established in 71.4% of DRE <i>vs.</i> 37.5% of non-refractory cases (P=0.003), with recurrent variants in <i>KCNQ2</i> and <i>SCN2A</i>. Univariate analysis identified abnormal muscle tone, epileptiform EEG, and definitive genetic diagnosis as significant risk factors for DRE (all P<0.05).</p><p><strong>Conclusions: </strong>Genetic etiology underlies most early-onset epilepsy cases. Abnormal muscle tone, epileptiform discharges on EEG, and definitive genetic diagnosis are risk factors for DRE, guiding early intervention.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"75"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a Charlson comorbidity index-based model for predicting the preterm premature rupture of the membrane.","authors":"Shu-Xin Zheng, Xun Ren, Qing-Qing Zhou, Wen-Wen Lin, Yu-Ping Cai, Feng-Yan Xie","doi":"10.21037/tp-2025-aw-745","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-745","url":null,"abstract":"<p><strong>Background: </strong>The Charlson comorbidity index (CCI) is a tool used to quantitatively assess the severity of comorbidities in patients. This study aimed to explore the predictive value of the CCI in preterm premature rupture of the membrane (PPROM).</p><p><strong>Methods: </strong>Data were collected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The continuous variables were analyzed using the T-test/one-way analysis of variance (ANOVA). Comparisons of categorical variables between groups were performed using the chi-square test. Colinearity analysis was used to exclude collinear variables. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were used to assess the prediction efficiency. The prediction model was established by the extreme gradient boosting (XGBoost), logistic, and Random Forest on the independent impact factors, and the areas under the curve (AUC), accuracy, precision, specificity, and F1 were used to assess the prediction efficiency of the model.</p><p><strong>Results: </strong>CCI was significantly higher in the PPROM group than in the term premature rupture of membranes (TPROM) group. The ROC (AUC: 0.535) and DCA indicated that CCI was limited in predicting the PPROM in clinical practice. The results of the logistic analysis showed that the CCI, platelet, age, red blood cell distribution width (RDW), and C-reactive protein (CRP) were the independent influencing factors of PPROM. The ROC results showed that the CCI-based model had a better prediction efficiency in predicting the occurrence of PPROM (AUC: 0.627).</p><p><strong>Conclusions: </strong>CCI was a risk factor for the PPROM. In addition, a risk prediction model based on the CCI and clinical features had a good prediction efficiency for PPROM.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"71"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular characteristics of a series of Chinese children with pseudohypoaldosteronism: a case series.","authors":"Ziying Wu, Junzan Li, Huiying Sheng, Xiuzhen Li, Zien Huang, Cuili Liang, Huifen Mei, Yunting Lin, Taolin Li, Wen Zhang, Aijing Xu","doi":"10.21037/tp-2025-1-844","DOIUrl":"https://doi.org/10.21037/tp-2025-1-844","url":null,"abstract":"<p><strong>Background: </strong>Pseudohypoaldosteronism (PHA) is a rare disorder characterized by renal resistance to mineralocorticoids, leading to hyperkalemia, hyponatremia, and metabolic acidosis. It is primarily classified into type I (PHAI), with subtypes including renal (caused by <i>NR3C2</i> mutation), systemic (caused by <i>SCNN1A/B/G</i> mutations), and secondary forms, and type II (PHAII), which is commonly associated with mutations in genes involved in the WNK signaling pathway (<i>WNK1, WNK4, KLHL3, CUL3</i>). However, comprehensive cohorts delineating the clinical and genetic spectrum of PHA in Chinese children are lacking.</p><p><strong>Case description: </strong>We present six unrelated Chinese children with PHA. Genetic testing enabled precise etiological classification: two with autosomal recessive systemic PHAI (harboring <i>SCNN1B</i> mutations) presented with severe neonatal salt-wasting; one with autosomal dominant renal PHAI (a heterozygous <i>NR3C2</i> mutation); three with PHAII (heterozygous <i>KLHL3</i> or <i>CUL3</i> mutations) exhibiting hyperkalemia and acidosis that were responsive to thiazides. Management was tailored to the subtype, including aggressive salt supplementation for systemic PHAI and thiazide diuretics for PHAII. Notably, one patient with systemic PHAI subsequently developed severe atopic dermatitis and extreme hyperimmunoglobulin E (4,080 IU/mL), a rarely documented comorbidity. Outcomes were generally favorable; however, one infant with systemic PHAI succumbed to refractory electrolyte imbalance, and another experienced persistent failure to thrive.</p><p><strong>Conclusions: </strong>In this study, we present six patients with different types of PHA (PHAI and PHAII), and describe their unique phenotypic, genetic characteristics. Our findings compellingly demonstrate that genetic testing is indispensable for precise subtyping, which in turn directs etiology-specific management and enables accurate prognostication, thereby optimizing long-term outcomes for affected children.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"82"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive end-expiratory pressure in pediatric acute respiratory distress syndrome: a narrative review.","authors":"Lauren Allen, Palen Mallory, Alexandre T Rotta, Kyle J Rehder, Andrew G Miller","doi":"10.21037/tp-2025-aw-684","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-684","url":null,"abstract":"<p><strong>Background and objective: </strong>Pediatric acute respiratory distress syndrome (PARDS) is associated with substantial morbidity and mortality. Positive end-expiratory pressure (PEEP) can support alveolar recruitment, improve oxygenation, and mitigate ventilator-induced lung injury (VILI). Despite its central role in lung-protective ventilation, evidence to guide PEEP titration in PARDS remains limited. This review summarizes physiologic principles, existing evidence, and bedside strategies for PEEP management in children.</p><p><strong>Methods: </strong>We performed a narrative review using PubMed from 1967 to 2025, limited to English-language studies. Search terms included \"pediatric acute respiratory distress syndrome\", \"positive end-expiratory pressure\", \"PEEP\", \"positive-pressure respiration\", \"mechanical ventilation\", \"pressure-volume curves\", \"electrical impedance tomography\", \"esophageal manometry\", \"stress index\", and \"ventilator-induced lung injury\". Reference lists from key publications and guidelines were also screened.</p><p><strong>Key content and findings: </strong>Among available strategies, utilization of the low PEEP:FiO₂ table from the ARDSnet study has the strongest evidence and is simple to apply at the bedside. Other approaches, such as compliance-based maneuvers, oxygenation-guided incremental-decremental maneuvers, stress index, pressure-volume curves, chest imaging, esophageal manometry, and electrical impedance tomography (EIT) lack robust pediatric outcome data. Of these methods for PEEP titration, esophageal manometry and EIT hold significant promise.</p><p><strong>Conclusions: </strong>Evidence supports maintaining PEEP at or above ARDSNet lower-table recommendations with close attention to physiologic response. Adjunctive monitoring with esophageal manometry or EIT may help balance recruitment and overdistension, but pediatric-specific trials are needed to define best practice. Standardized multicenter studies will be essential to establish evidence-based PEEP strategies in PARDS.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"85"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA (MtDNA) 3243 A>G mutation associated with recurrent cholangitis post-Kasai procedure in biliary atresia.","authors":"Jie Sun, Yanan Zhang, Dayan Sun, Jinshi Huang","doi":"10.21037/tp-2026-1-0137","DOIUrl":"https://doi.org/10.21037/tp-2026-1-0137","url":null,"abstract":"","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"94"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen strategies in pediatric sedation: a clinical and statistical reassessment.","authors":"Tom Giedsing Hansen, Thomas Engelhardt","doi":"10.21037/tp-2025-1-889","DOIUrl":"https://doi.org/10.21037/tp-2025-1-889","url":null,"abstract":"","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"67"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}