Italian Journal of Pediatrics最新文献

{"title":"Brain-computer interfaces: innovations and challenges in the field of cerebral palsy rehabilitation.","authors":"Yize Chen, Yuling Gao, Jiaqi Zhou, Zhenni Zhang, Junwei Zong, Yong Liu","doi":"10.1186/s13052-026-02361-z","DOIUrl":"10.1186/s13052-026-02361-z","url":null,"abstract":"<p><p>Brain-computer interfaces have shown great potential in the rehabilitation of Cerebral palsy, improving the ability of children with cerebral palsy to perform activities of daily living by replacing and restoring lost neurological functions, as well as accurately evaluating cognitive functions and facilitating rehabilitation in conjunction with various rehabilitation techniques. Nonetheless, numerous challenges persist in the application of brain-computer interfaces for cerebral palsy. Future research should focus on developing enhanced and more dependable brain-computer interfaces, advancing the hardware, and establishing ethical and regulatory frameworks to facilitate their utilisation in cerebral palsy rehabilitation.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of lung ultrasound in differentiating and monitoring complicated pediatric pneumonia: a prospective diagnostic accuracy study.","authors":"Rehab Elmeazawy, Ebtsam Ahmed Attia, Osama Toema, Nancy Mohamed Elgharabawy, Ahmed Harkan, Ahmed M Elniny","doi":"10.1186/s13052-026-02341-3","DOIUrl":"10.1186/s13052-026-02341-3","url":null,"abstract":"<p><strong>Background: </strong>Lung ultrasound (LUS) is an established diagnostic tool for pediatric pneumonia, yet its utility as radiation-free alternative to computed tomography (CT) for monitoring disease progression and differentiating complicated phenotypes, specifically necrotizing pneumonia (NP) and parapneumonic effusion (PPE), has not been prospectively validated in a single comparative cohort. This study aimed to evaluate the diagnostic and longitudinal performance of LUS, including a quantitative LUS score, in children with community-acquired pneumonia (CAP), CT-confirmed NP, and PPE, and to evaluate the diagnostic accuracy and longitudinal performance of LUS for identifying and monitoring complicated pediatric pneumonia, including its potential as a radiation-free follow-up tool.</p><p><strong>Methods: </strong>This prospective single-center diagnostic accuracy study enrolled 257 children diagnosed with CAP (n = 116), NP (n = 54), and PPE (n = 87). NP was confirmed by CT in all 54 cases; LUS was performed by trained operators at admission and on day five as a paired assessment against CT and chest radiograph findings. LUS qualitative features and quantitative scores were compared between groups and over time. Multivariable regression and ROC analysis were performed to assess diagnostic accuracy and identify predictors of clinical outcome.</p><p><strong>Results: </strong>At admission, NP and PPE showed significantly higher LUS scores and more frequent absent lung sliding and heterogeneous hypoechoic consolidation than CAP (p < 0.001). A LUS score cutoff of > 8 demonstrated strong diagnostic performance at both time points (admission AUC: 0.881, sensitivity 79.02%; Day 5 AUC: 0.861, specificity 93.86%), supporting its potential role as an early screening marker and as a radiation-free bedside monitoring tool during follow-up. Longitudinal LUS assessment demonstrated significant re-aeration by Day 5 (p < 0.001), evidenced by an increased proportion of separated B-lines (35.0% to 54.9%) and a reduction in lung consolidation. On multivariable analysis, higher LUS scores independently predicted longer hospitalization on both admission (β = 0.221, p < 0.001) and Day 5 (β = 0.215, p < 0.001), and elevated D-dimer on admission (β = 0.334, p < 0.001) and Day 5 (β = 0.386, p < 0.001).</p><p><strong>Conclusion: </strong>A LUS score > 8 showed promising diagnostic performance for identifying complicated pediatric pneumonia at admission and during Day 5 follow-up. Although internal bootstrap validation supported the stability of its performance, prospective validation in independent cohorts is required before implementation as a CT-sparing follow-up strategy.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retractile testis: time to reconsider the \"benign variant\" classification in light of histopathological evidence.","authors":"Jia You, Hai-Tao Chen","doi":"10.1186/s13052-026-02354-y","DOIUrl":"10.1186/s13052-026-02354-y","url":null,"abstract":"","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-label prescribing in pediatrics: between regulatory gaps and clinical evidence.","authors":"Federico Marchetti, Maurizio Bonati, Antonio Clavenna","doi":"10.1186/s13052-026-02348-w","DOIUrl":"10.1186/s13052-026-02348-w","url":null,"abstract":"<p><p>Despite important regulatory progress, evidence supporting the use of medicines in children remains limited, and off-label prescribing continues to be common in pediatric practice. Regulatory initiatives such as the United States Pediatric Research Equity Act (PREA) and the European Pediatric Regulation were designed to increase the labelling information relevant to paediatric use, yet important gaps persist because studies are often delayed, incomplete, or absent for many conditions and formulations. This article addresses the common misconception that off-label prescribing is always inappropriate or unsupported and argues that this interpretation is not supported by the current evidence. In reality, many off-label treatments in pediatrics are supported by scientific evidence, clinical guidelines, and consolidated experience, even when formal regulatory approval is lacking. Examples involving pediatric oncology, child psychiatric disorders, and supportive care illustrate how effective therapies may remain off-label despite becoming standards of care. The Italian experience reflects these broader challenges. Studies have shown that off-label prescribing is structural rather than exceptional in pediatrics, while national initiatives such as Law 648/96 and pediatric formularies have sought to support evidence-based prescribing beyond regulatory boundaries. It is necessary to overcome the simplistic distinction between prescriptions that comply with the indications and appropriate prescriptions. A more rational framework should distinguish unsupported off-label use from evidence-based off-label prescribing. Reducing the pediatric evidence gap therefore requires not only more pediatric research, but also recognition of rational off-label prescribing as an essential component of pediatric clinical practice.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for caffeine administration in preterm infants: route, dosing, monitoring, and adjunctive interventions - a systematic review.","authors":"Alaa A M Osman, Chiara Russo, Maria Rojas-Reyes, Franciszek Borys, Michelle Fiander, Roger Soll, Matteo Bruschettini, Greta Sibrecht","doi":"10.1186/s13052-026-02344-0","DOIUrl":"10.1186/s13052-026-02344-0","url":null,"abstract":"<p><strong>Introduction: </strong>Caffeine is widely used in preterm infants, yet the optimal administration strategy remains unclear. This systematic review aims to evaluate different caffeine administration approaches, including route, frequency, dose modifications, and co-administration with surfactant in preterm infants.</p><p><strong>Methods: </strong>We searched three databases and two trial registries up to October 2024. Data collection and analysis followed Cochrane methodology; certainty of evidence was assessed using GRADE; and reporting followed PRISMA.</p><p><strong>Results: </strong>Three RCTs were identified, two provided data for analyses: one study (38 infants) on route of administration (intravenous versus oral caffeine) and one study (40 infants) on frequency of administration (once versus twice daily). The evidence is very uncertain about the effects of intravenous versus oral administration on: mortality (RR 0.14, 95% CI 0.01-2.59); mechanical ventilation duration (MD 1.00, 95% CI -8.05 to 10.05); hospital stay (MD 8.00, 95%CI -5.35-21.35); severe intraventricular hemorrhage (RR 1.00, 95%CI 0.29-3.43); and chronic lung disease (RR 5.00, 95%CI 0.26-97.70). The evidence is very uncertain about the effects of twice-daily versus once-daily caffeine on: mortality (RR 1.00, 95%CI 0.29-3.45); ventilation duration (MD 0.81, 95%CI -7.56-9.18); and hospital stay (MD -2.70, 95%CI -8.12-2.72). We found no studies on caffeine dose modifications and co-administration with surfactant. Two trials on adjusting caffeine dose and route of administration are ongoing.</p><p><strong>Conclusion: </strong>Although caffeine clearly benefits preterm infants, evidence guiding optimal administration strategies, such as route, frequency, and dose modifications, is limited. High-quality studies are urgently needed to inform clinical practice and guidelines.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the myocardial functions of the forgotten right ventricle in children with nephrotic syndrome utilizing traditional echocardiography, two-dimensional speckle tracking and three-dimensional echocardiography.","authors":"Amira Hussein, Shaimaa Rakha, Asmaa Bakr, Alshaymaa Ahmed Ali, Ayman Hammad, Mona Hafez, Mai S Korkor","doi":"10.1186/s13052-026-02335-1","DOIUrl":"10.1186/s13052-026-02335-1","url":null,"abstract":"<p><strong>Background: </strong>Primary nephrotic syndrome (NS) is associated with systemic effects that may impact cardiac function, although several studies have explored left ventricle in children with NS. Few studies investigated right ventricle (RV) in this disease. Therefore, the study aimed to provide a comprehensive evaluation of RV functions in children with primary NS using echocardiography.</p><p><strong>Methods: </strong>A case-control observational study was conducted from January 2022 to August 2024 on 40 primary NS patients with steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS), alongside 40 healthy controls. All participants underwent RV assessments using conventional parameters, tissue Doppler imaging (TDI), two-dimensional speckle-tracking echocardiography (2D STE), and three-dimensional echocardiography (3DE).</p><p><strong>Results: </strong>Significantly lower s', e' in NS patients compared to controls, especially lower in SRNS compared to SSNS. Significantly higher E/e' and Tei index was detected in the NS group compared to controls (p = < 0.001) and more pronounced in SRNS. RV free wall strain longitudinal strain (RVFWLS) and RV four chamber longitudinal strain (RV4CSL) were significantly reduced in NS group compared to controls. 3D auto RV-derived ejection fraction (EF), TAPSE, stroke volume and septal strain were lower in NS compared to controls(p = < 0.001); however, there are no significant differences between SSNS and SRNS. Significant correlations were detected between some echocardiographic parameters and serum cholesterol, albumin, and creatinine.</p><p><strong>Conclusions: </strong>Integrative use of variable echocardiographic modalities allows detection of subclinical alterations in RV function in children with primary NS, with more affected parameters in SRNS. Therefore, regular surveillance of RV functions in primary NS should be considered.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum IL-38 and the rs7599662 polymorphism: novel biomarkers for pediatric idiopathic nephrotic syndrome.","authors":"Sherin Khamis Hussein, Maha Hosni Morsi, Omayma O Abdelaleem, Doaa Ezzat Sayed Ahmed, Doha Elsayed Ahmed Hassanein, Marwa A Ali, Shaimaa Abdelbadie, Ahmed Mohamed Gamal El Din Wahba, Asmaa Younis Elsary, Heba Safar, Reham Fares","doi":"10.1186/s13052-026-02327-1","DOIUrl":"10.1186/s13052-026-02327-1","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disorder in children and is characterized by a variable response to corticosteroid therapy. Interleukin-38 (IL-38), an anti-inflammatory cytokine, and its gene polymorphisms may influence disease susceptibility and treatment outcomes. This study investigated the associations between serum IL-38 levels, the rs7599662 gene polymorphism, and disease presence in pediatric INS patients.</p><p><strong>Methods: </strong>This case‒control study included 88 pediatric INS patients and 74 age- and sex-matched healthy controls. Patients were categorized as steroid sensitive (50%), steroid dependent (25%), or steroid resistant (25%). Serum IL-38 was measured by ELISA, and rs7599662 (C/T) genotyping was performed via real-time PCR. Statistical analyses included nonparametric tests, chi-square tests, Spearman correlation, and receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>Serum IL-38 levels were significantly lower in patients than in controls (17.9 ± 11.4 vs. 38.8 ± 35.6 ng/L, p < 0.001). IL-38 was negatively correlated with age (r = -0.28, p = 0.01), systolic blood pressure (r = -0.28, p = 0.01), and urinary protein (r = -0.38, p = 0.001). ROC analysis revealed that IL-38 had moderate diagnostic performance (AUC = 0.687, p < 0.001), with 73.7% sensitivity and 63.8% specificity at a cutoff of 18.773 ng/L. The CT genotype was significantly more common in patients (p = 0.003), with a protective association observed for the TT genotype under a recessive model (p = 0.002). Serum IL-38 levels did not differ among steroid-sensitive, dependent, or resistant subgroups (p = 0.32).</p><p><strong>Conclusion: </strong>This first report of reduced serum IL-38 and the rs7599662 polymorphism in pediatric INS suggests a role for impaired anti-inflammatory responses in disease pathogenesis. Serum IL-38 shows promise as a diagnostic biomarker and may reflect disease pathophysiology, but does not predict steroid responsiveness. These hypothesis-generating findings require validation in larger, prospective, multicenter studies to establish their clinical utility. The primary value of this work lies in generating testable hypotheses for future confirmatory studies rather than providing definitive mechanistic answers.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden hypertension and early cardiac alterations: insights from ambulatory blood pressure monitoring in children and adolescents.","authors":"Mona Saber Mohamed Kamel, Sonia Ali El-Saiedi, Ayman Elsayed Shafei, Ashraf Abdel Baky Salama, Dalia Gaber Sos Boles, Mahmoud Othman Aboudeif","doi":"10.1186/s13052-026-02319-1","DOIUrl":"10.1186/s13052-026-02319-1","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is increasingly recognized as a significant health concern among children and adolescents, often associated with obesity and lifestyle choices. Early-onset hypertension can elevate the risk of cardiovascular diseases in adulthood, making early detection crucial. As it is often asymptomatic, routine screening is essential. Schools serve an effective environment for identifying at-risk students. Accurate diagnosis requires standardized protocols because blood pressure (BP) can vary based on age, sex, and height. Addressing pediatric hypertension is key to reducing long-term cardiovascular morbidity and mortality.</p><p><strong>Methods: </strong>The study included 354 students: 234 primary grade 3 students (8-9 years) and 120 secondary grade 9 students (~ 15 years). Assessments included medical history, physical examination (weight, height, BMI, and BP). BP was measured using standardized methods and classified by established percentiles. Ambulatory Blood Pressure Monitoring (ABPM) was performed for students with elevated BP to analyze 24-hour readings, dipping status, and pulse pressure, and to classify hypertension. Echocardiography was performed on all students with elevated BP.</p><p><strong>Results: </strong>Significant differences were observed in BMI and hypertension prevalence between Grade 3 and Grade 9. In Grade 3, 45.7% were underweight, 31.9% had normal BMI, and 22% were overweight or obese; in Grade 9, 81.5% were overweight or obese. Clinic-based hypertension was higher in Grade 3 (15.4%) compared to Grade 9 (12.5%), sustained hypertension was confirmed by ABPM to rule out white-coat hypertension, results correlated with BMI Z scores and lifestyle. Despite being asymptomatic, cardiac changes were observed: the mean interventricular septal thickness (IVSd) was 0.75 cm in Grade 3 versus 1.07 cm in Grade 9.</p><p><strong>Conclusions: </strong>ABPM is crucial for accurate diagnosis of hypertension in schoolchildren and adolescents, clarifying the relationship between obesity, lifestyle, and elevated BP. The study underscores that early cardiac remodeling was already present in asymptomatic children, emphasizing the need for early interventions, including weight management and lifestyle modifications, to reduce hypertension and future cardiovascular risk.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between lipid metabolism and Henoch-Schönlein purpura nephritis in children: a systematic review and meta-analysis.","authors":"Xu Zhang, Zhenlin Yang, Jingjing Guo, Jinzi Li","doi":"10.1186/s13052-026-02330-6","DOIUrl":"10.1186/s13052-026-02330-6","url":null,"abstract":"<p><strong>Background: </strong>Henoch-Schönlein purpura (HSP)is the most common childhood vasculitis, and renal involvement (HSPN) significantly worsens its prognosis. Noninvasive correlates of renal involvement are therefore of interest. Dyslipidemia often coexists with renal inflammation. Clarifying this association is essential to understand the metabolic perturbations in HSPN. However, although dyslipidemia has been associated with HSPN, its exact mechanism remains unclear from an evidence-based.</p><p><strong>Methods: </strong>A comprehensive search was performed using PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal (VIP), and the Chinese Medical Journal full-text databases from their inception to December 25, 2024. Primary outcomes compared levels of total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) between the HSPN group and the HSP group; secondary outcomes included study methodology, publication date, sample size, and quality assessment scores. Study quality was assessed using modified NOS scales, with inter-rater reliability measured by Cohen's kappa. Statistical analysis was performed using Stata 16.0 to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were limited by the paucity of data regarding the timing of blood sampling relative to corticosteroid initiation and renal onset.</p><p><strong>Results: </strong>Eighteen studies were included. Meta-analysis revealed that patients with HSPN had significantly higher levels of TC, TG, and LDL compared with patients with HSP without nephritis. The pooled estimates were TC (SMD = 0.55, 95% CI = 0.36 to 0.75; I² = 89.9%, P < 0.001), TG (SMD = 0.47, 95% CI = 0.29 to 0.65; I² = 69.8%, P = 0.001), and LDL (SMD = 0.37, 95% CI = 0.12 to 0.61; I² = 76.1%, P < 0.001). No significant difference was observed for HDL (SMD = - 0.87, 95% CI = - 1.89 to 0.14; I² = 97.9%, P < 0.001).</p><p><strong>Conclusion: </strong>Elevated levels of TC, TG, and LDL are observed in patients with HSPN, underscoring a robust association between lipid dysregulation and renal involvement. However, significant heterogeneity, coupled with the lack of pretreatment baseline data, precludes causal inference and precludes utility in early prediction. Prospective studies measuring pretreatment baseline lipids prior to renal onset are warranted to validate these findings.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome resequencing with multidimensional annotation revealed pathogenic networks in sirenomelia.","authors":"Zefeng Zhu, Wanting Hao, Ziyu Wan, Tianhao Ma, Yao Xu, Yu Wang, Wei Gu","doi":"10.1186/s13052-026-02307-5","DOIUrl":"https://doi.org/10.1186/s13052-026-02307-5","url":null,"abstract":"<p><strong>Background: </strong>Sirenomelia is a rare and lethal congenital malformation representing the most severe form of caudal dysgenesis, with a stillbirth rate of up to 53%. The genetic basis of sirenomelia remains poorly understood. Consequently, in this study, we aimed to comprehensively characterize genomic variants and explore potential pathogenic mechanisms in sirenomelia.</p><p><strong>Methods: </strong>Whole-genome resequencing was performed on peripheral blood mononuclear cells from one patient with sirenomelia and one matched healthy newborn. Variants were identified and prioritized using the gnomAD and ClinVar population databases. single nucleotide polymorphisms (SNP)/InDel and structural variants were further analyzed using multidimensional functional enrichment approaches.</p><p><strong>Results: </strong>A total of 116 candidate genes harboring rare and potentially deleterious SNP/InDel variants were identified, including BMP5 and BMP6. Structural variant analysis revealed 549 sirenomelia-specific variants involving genes such as TWSG1 and Retinoic acid receptor beta (RARB). Functional enrichment revealed that these genes were predominantly involved in key developmental pathways, including BMP, WNT and TGF-β signaling. Integrated analysis indicated convergent disruption of signaling networks regulating posterior axis development, particularly those associated with kidney formation, cloacal partitioning, and limb patterning.</p><p><strong>Conclusion: </strong>These findings support a multilayered pathogenic model in which genetic variants collectively disrupt the core developmental pathways involved in posterior axis formation, vasculogenesis, and organogenesis. Our findings provide a genomic framework for understanding the molecular basis of sirenomelia and identify potential targets for future research and clinical applications.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"52 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}