Italian Journal of Pediatrics最新文献

{"title":"Clinical and functional characterization of the GABRB3 p.Met80Val variant in early-onset epilepsy with long-term follow-up.","authors":"Ran Hua, Junhong Jiang, Baotian Wang, Zihao Zhu, Juan Wang, De Wu, Li Yang","doi":"10.1186/s13052-025-02046-z","DOIUrl":"10.1186/s13052-025-02046-z","url":null,"abstract":"<p><strong>Background: </strong>GABRB3 encodes the β3 subunit of the GABA_A receptor, which is a crucial component in inhibitory neurotransmission within the central nervous system. GABRB3 variants are associated with developmental and epileptic encephalopathy 43. Noteworthy, GABRB3 variants can result in both gain-of-function and loss-of-function effects. However, their precise functional and clinical implications remain unknown.</p><p><strong>Methods: </strong>Whole-exome sequencing, validation of the identified GABRB3 variants using Sanger sequencing, and structural modeling were done to assess the potential impact of these variants on receptor function. Functional analyses included quantification of GABRB3 protein expression levels, subcellular localization using fluorescence microscopy, and electrophysiological recordings of α1β3γ2 and α1β3(M80V)γ2 receptor complexes to evaluate channel properties.</p><p><strong>Results: </strong>A heterozygous de novo GABRB3 variant (NM_000814.6: c.238 A > G, p.Met80Val) was identified in a 16-year-old female who developed absence seizures at one year and exhibited persistent EEG abnormalities over the subsequent decade. She exhibited mild intellectual disability, poor academic performance, and limited language skills but maintained school attendance and social engagement. Structural modeling suggested that the p.Met80Val variant compromises the structural integrity of the protein. Functional assays revealed a 2.6-fold increase in GABRB3 protein expression and enhanced fluorescence intensity, with most of the protein localized in the cytoplasm. Electrophysiological recordings demonstrated significantly increased current amplitude, heightened GABA sensitivity, and reduced zinc sensitivity. These findings indicated that the p.Met80Val variant altered the receptor conformation or its zinc-binding site, weakening zinc-mediated inhibition.</p><p><strong>Conclusion: </strong>This study reports the ninth case of a recurrent GABRB3 p.Met80 variant and highlights its potential as a hotspot missense variant. The findings underscore its pathogenicity after a long follow-up period of more than ten years supported by continuous EEG monitoring. These findings enhance our understanding of the functional changes among GABRB3 variants and their role in the pathogenesis of epilepsy.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"195"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336578","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":"Intubating laryngeal airway vs. direct laryngoscope: a crossover randomized controlled neonatal manikin trial.","authors":"Chiara Monfredini, Francesco Cavallin, Paul Ouedraogo, Leila Ezzahraoui, Elisa Pasta, Daniele Trevisanuto, Paolo Ernesto Villani","doi":"10.1186/s13052-025-01988-8","DOIUrl":"10.1186/s13052-025-01988-8","url":null,"abstract":"<p><strong>Background: </strong>We aimed to compare endotracheal intubation through a laryngeal mask vs. using a direct laryngoscope in a manikin simulating a term infant.</p><p><strong>Methods: </strong>A randomized, controlled, crossover (AB/BA) trial of intubation through a laryngeal mask vs. a direct laryngoscope in a manikin simulating a term infant. Thirty-four tertiary neonatal intensive care unit consultants and pediatric residents who had previous experience with intubating laryngeal airway and direct laryngoscopy participated. The primary outcome measure was the success of the procedure at the first attempt. The secondary outcome measures included the total time of endotracheal tube positioning and participant's opinion on insertion difficulty and overall difficulty.</p><p><strong>Results: </strong>Success at first attempt was 34/34 with the laryngeal mask (100%) and 26/34 with the direct laryngoscope (76%) (difference in percentage 24%, 95% confidence interval 5-41%; p = 0.008). Median time of endotracheal tube positioning was 24 s (IQR 19-30) with both devices (p = 0.86). Insertion difficulty (p = 0.96) and overall difficulty (p = 0.99) were not statistically different between the devices.</p><p><strong>Conclusions: </strong>In a term infant manikin model, positioning the endotracheal tube through the laryngeal mask increased the success at the first attempt compared to direct laryngoscopy, without extending the duration of the procedure or affecting the perceived difficulty.</p><p><strong>Registration: </strong>clinicaltrial.gov NCT06263790. Registered 16 February 2024, https://clinicaltrials.gov/study/NCT06263790 .</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"196"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336580","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":"Admission rate for bronchiolitis of newborns and infants in Italian neonatal intensive care units in 2021: a survey of the Italian Society of Neonatology - Intensive Care of Early Childhood Study Group.","authors":"Nunzia Decembrino, Roberta Leonardi, Tiziana Fedeli, Luana Conte, Chiara Distefano, Nicola Pozzi, Valeria Fichera, Ferdinando Spagnuolo, Camilla Gizzi, Fabio Mosca, Luigi Orfeo, Eloisa Gitto","doi":"10.1186/s13052-025-01977-x","DOIUrl":"10.1186/s13052-025-01977-x","url":null,"abstract":"<p><strong>Background: </strong>The shortage of Pediatric Intensive Care Unit (PICU) beds among some Italian regions is a major concern, especially during epidemics. During respiratory syncytial virus (RSV) bronchiolitis peak, Neonatal Intensive Care Units (NICU) often admit infants and toddlers requiring advanced respiratory support. We conducted a survey to quantify children hospitalized for RSV bronchiolitis in NICU in 2021 and to examine the adherence to treatment guidelines.</p><p><strong>Methods: </strong>Early Childhood Intensive Care Working Group of the Italian Society of Neonatology (SIN) conducted a survey distributed to SIN Network NICUs. The modified Delphi method was used to prepare the survey; duplicate responses were excluded. Analysis evaluated percentages.</p><p><strong>Results: </strong>Response rate was 67% (78/117 NICUs). Geographic distribution of responding centers was: 51% Southern-Islands, 38% North, 11% Center; 50% were Territorial Hospitals, 20% University Hospitals. Of respondents, 55% have 5-10 NICU beds; 70% routinely admit children > 44 weeks postconceptional age and > 28 days old, with a rate of < 10 toddlers/year in 50% of cases, 10-20 toddlers/year in 25% of cases and > 20 toddlers/year in 15%. In 2021, 40% of NICUs admitted < 10 bronchiolitis cases, 29% 11-20 cases. RSV was the leading cause of bronchiolitis. Reasons for NICU admission were respiratory distress syndrome (92%), feeding difficulties (58%), comorbidities (20%). High-flow oxygen (87%) and non-invasive ventilation (60%) were common respiratory supports provided; 10% of patients needed invasive ventilation. Treatment included inhaled steroids (46%), bronchodilators/systemic steroids (32%), antibiotics (40%); 60% of centers did not use sedation during NIV; 30% used midazolam, 13% dexmedetomidine, < 10% fentanyl.</p><p><strong>Conclusions: </strong>Our survey highlights that during the RSV epidemic, NICUs admitted toddlers to receive advanced respiratory support unavailable in pediatric ICUs. Most of the NICUs admitted fewer than 10 toddlers per year and less than 10 bronchiolitis, posing skill challenges for medical staff. This supports SIN's proposal to identify some \"extended NICUs\" in regions with limited PICU beds, to centralize toddlers after an adequate training to gain knowledge/technical skills specific of pediatric critical care. This would help to overcome the PICU beds storage. Adherence to bronchiolitis management guidelines resulted suboptimal, with frequent but unrecommended use of inhaled steroids, bronchodilators, and antibiotics.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"192"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316924","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":"When infection hurts: golden rules for managing pediatric skin and soft tissue infections.","authors":"Giangiacomo Nicolini, Valentina Frasca Polara, Matteo Calvi, Marc García-Lorenzo, Miriam Massese, Gregorio Paolo Milani, Roberta Parrino, Enrico Vidal, Claudia Colomba","doi":"10.1186/s13052-025-01994-w","DOIUrl":"10.1186/s13052-025-01994-w","url":null,"abstract":"<p><p>Skin and Soft Tissue Infections (SSTIs) are common in pediatric patients, accounting for nearly 25% of clinical visits. These infections can range from mild to life-threatening and include a severe subset known as Acute Bacterial Skin and Skin Structure Infections (ABSSSI). Prompt diagnosis and appropriate antibiotic use are crucial for optimizing patient outcomes while minimizing adverse effects and antimicrobial resistance. However, empirical treatment often becomes necessary due to the lack of culture specimens, making local epidemiology and clinical presentation key factors in treatment decisions. This expert opinion paper aims to outline the \"golden rules\" for the management of SSTIs in children, focusing on achieving microbiological clearance, clinical improvement, and effective control of symptoms, such as fever and pain, which significantly impact the child's well-being. These emphasize the principles of antimicrobial stewardship, recommending early diagnosis with appropriate laboratory tests, rational empiric therapy, and prompt switch to targeted therapy based on microbiological findings, as well as proper fever and pain management. The paper also highlights the importance of a multidisciplinary approach for complex cases, optimal dosing, and effective communication with patients' families to improve treatment compliance. Furthermore, antibiotic therapy should be selected to reduce hospital stay and facilitate home-based continuity of care, while follow-up and strengthening of the hospital-territory network are critical for continuity of care after discharge. These recommendations aim to optimize the management of pediatric SSTIs by ensuring comprehensive care from initial diagnosis to post-discharge follow-up, promoting the rational use of antibiotics, and ultimately improving clinical outcomes and quality of life for children and their families.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"194"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316926","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":"Neonatal hereditary spherocytosis: a case report.","authors":"Carolina Coramusi, Natalia Lucangeli, Sarah Vadalà, Pasquale Parisi, Maria Eleonora Scapillati","doi":"10.1186/s13052-025-02049-w","DOIUrl":"10.1186/s13052-025-02049-w","url":null,"abstract":"<p><strong>Background: </strong>Hereditary spherocytosis is a genetic disorder affecting red blood cell membranes, leading to increased destruction and haemolysis. In neonates, it ranges from asymptomatic to severe cases with anaemia, jaundice, and spleen issues. Early diagnosis through clinical, laboratory, and genetic tests is vital for prognosis. This clinical case is presented due to the rarity of neonatal-onset spherocytosis, providing an opportunity for a literature review.</p><p><strong>Case presentation: </strong>A full-term baby was born via vaginal delivery with a family history of hereditary spherocytosis. The patient was discharged without complications but was later hospitalized for an unrelated issue, during which haemolytic anemia was detected, leading to the beginning of the diagnostic process and subsequent onset of appropriate therapy with a positive outcome.</p><p><strong>Conclusions: </strong>In cases of neonates with jaundice or anemia, it is crucial to consider neonatal spherocytosis among the differential diagnoses, as early diagnosis allows for appropriate therapy and enables the patient to maintain a normal quality of life.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"193"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316925","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":"The dysregulation and regulatory mechanism of long non-coding RNA LBX2-AS1 in children with epilepsy.","authors":"Qian Li, Ning Li","doi":"10.1186/s13052-025-02045-0","DOIUrl":"10.1186/s13052-025-02045-0","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a long-lasting neurological condition distinguished by recurring seizures, and related to oxidative stress and inflammation. This study investigates the effects of long non-coding RNA LBX2-AS1 on childhood epilepsy.</p><p><strong>Methods: </strong>There were 165 epilepsy epileptic and 206 healthy children enrolled in this study. Relative LBX2-AS1, miR-873-5p, and HNRNPK expression levels were assessed using RT-PCR. Diagnostic value of LBX2-AS1 was evaluated by ROC curve. Epilepsy cell model was constructed in HT22 cells. Cell viability was assessed by CCK-8 kit. Cell apoptosis was analyzed by flow cytometer. Oxidative stress factors (SOD, GSH, LDH) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were evaluated by ELISA kits. Target association was validated using dual-luciferase reporter assays. Function analysis for miR-873-5p target genes was analyzed by GO, KEGG, and PPI.</p><p><strong>Results: </strong>LBX2-AS1 was upregulated in epilepsy and had a high diagnostic value for epilepsy (AUC = 0.880, sensitivity = 80.6%, specificity = 82.0%, cutoff value = 1.14). The upregulation of LBX2-AS1 in cell model might decrease cell viability, increase apoptosis, and elevate oxidative stress and inflammation via negatively controlled miR-873-5p. Target genes of miR-873-5p were enriched in pathways related to oxidative stress, inflammation responses, and magnesium ion transmembrane transporter activity of neuronal cells. HNRNPK had the highest interaction degree with other target genes.</p><p><strong>Conclusion: </strong>LBX2-AS1 is upregulated in epilepsy and is associated with increased oxidative stress, inflammation, and apoptosis via mediating miR-873-5p/HNRNPK axis in epilepsy cell model.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"189"},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302076","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 features and outcomes in pediatric patients with cortical laminar necrosis: a single-center retrospective study.","authors":"Zhanwei Zhang, Zou Pan, Lifen Yang, Fang He, Fangyun Liu, Jing Peng","doi":"10.1186/s13052-025-02038-z","DOIUrl":"10.1186/s13052-025-02038-z","url":null,"abstract":"<p><strong>Background: </strong>Cortical laminar necrosis (CLN) is a selective cortical necrosis primarily involving layer 3 of the cortex. Its causes, clinical features, and outcomes in pediatric patients remain unclear due to limited cases.</p><p><strong>Methods: </strong>Pediatric CLN patients from Xiangya Hospital from January 2014 to December 2024 were enrolled. Clinical data, brain magnetic resonance imaging (MRI), and Modified Rankin Scale (mRS) for neurological outcomes were analyzed.</p><p><strong>Results: </strong>Among 59 enrolled patients, causes included hypoxic-ischemic encephalopathy (HIE), hereditary and metabolic, infectious, vascular, and trauma. Seizures and consciousness changes were common symptoms. Infectious and hereditary and metabolic causes were linked to status epilepticus (P < 0.001), while vascular causes were associated with hemiplegia (P < 0.001). HIE patients had poorer prognosis (P = 0.038). MRI showed earlier hyperintensity on diffusion weighted imaging (DWI) than enhancement in T1 contrasted sequence, as well as T1 sequence and fluid attenuated inversion recovery (FLAIR). Bilateral involvement was seen in all HIE cases, while hereditary and metabolic causes often showed unilateral involvement (P < 0.001). Frontal lobe involvement was common in vascular and trauma cases (P = 0.017), and all patients with HIE exhibited involvement in the parietal and occipital lobes. While infectious cases frequently involved the insular and temporal lobes, most patients exhibited brain atrophy/encephalomalacia at follow-up. Three patients showed new CLN and two patients exhibited persistent CLN during MRI follow-up.</p><p><strong>Conclusion: </strong>HIE, hereditary/metabolic, infectious, vascular, and trauma are the main causes of pediatric CLN, with distinct clinical features and outcomes.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"188"},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302064","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":"Optimizing antimicrobial routes: risk factor analysis for intravenous therapy in children with preseptal orbital cellulitis.","authors":"Roberto Privato, Emanuela Inserra, Francesco Pezzoli, Alessia Nucci, Stefano Masi, Elena Chiappini, Giuseppe Indolfi, Sandra Trapani, Luisa Galli, Elisabetta Venturini","doi":"10.1186/s13052-025-01931-x","DOIUrl":"10.1186/s13052-025-01931-x","url":null,"abstract":"<p><strong>Background: </strong>The optimal route of antimicrobial administration for preseptal orbital cellulitis (OC) in children remains uncertain. While mild cases may be managed with oral therapy, distinguishing between mild and severe presentations is challenging. The recently proposed ASSET score offers a tool for assessing the severity of skin and soft tissue infections, but prospective validation in large cohorts of preseptal OC is lacking. As a result, most patients with periorbital infections are admitted for intravenous (IV) antibiotics. This study aims to identify clinical and laboratory features predictive of severe preseptal OC requiring IV treatment.</p><p><strong>Methods: </strong>A retrospective study was conducted at Meyer Children's Hospital IRCCS, Florence, reviewing outpatient records for OC cases from January 2017 to June 2024. Data on age, sex, clinical presentation, blood tests, and management were collected.</p><p><strong>Results: </strong>Previously initiated oral therapy was associated with the need for IV therapy (p < 0.001), as well as the presence of fever (p < 0.001), and severe eyelid swelling (p < 0.001). The median ASSET score was higher in patients with preseptal OC requiring IV therapy (p < 0.001). Differences in laboratory findings were noted between children with preseptal OC managed with and without IV antibiotics.</p><p><strong>Conclusions: </strong>Previous trials of oral antibiotics, systemic features, and severe swelling influence clinicians' decisions to initiate IV antibiotics in preseptal OC. If validated for preseptal OC, the application of the ASSET score could significantly reduce the number of children treated with IV antibiotics. Ancillary blood tests may be useful for detecting preseptal OC requiring IV treatment.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"190"},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302065","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":"POLR3A rare variants in a patient with intellectual disability, ataxic gait and cortical malformations: a case-report.","authors":"Caterina Angela Florio, Federica Mirabella, Adriana Prato, Andrea Longhitano, Rita Barone, Renata Rizzo","doi":"10.1186/s13052-025-02024-5","DOIUrl":"10.1186/s13052-025-02024-5","url":null,"abstract":"<p><strong>Background: </strong>Recessive mutations in POLR3A exhibit considerable phenotypic diversity, spanning from severe childhood-onset hypomyelinating leukodystrophic syndrome to less severe gait disorders, which may present later in life and may be accompanied by additional non-neurological symptoms. In this study, we report a new case of rare POLR3A variants in a 6-year-old female patient sharing common genetic and neuropsychological profiles of POLR3-related disorders, although without revealing the classic MRI phenotype and severe clinical signs of POLR3-related leukodystrophy, such as diffuse hypomyelination.</p><p><strong>Case presentation: </strong>Our probe was born after full term pregnancy complicated by Intrauterine Growth Restriction and risk of preterm birth treated with tocolytics during the last weeks of pregnancy. On the second day of life, tremors in the lower and upper limbs were detected and lasted until the second month of life. At the age of 6 months, she was diagnosed with hypotonia. The child showed a delay in the stages of psychomotor development and a slowing of the language. Brain MRI performed at the age of 5 years revealed mild and symmetrical ectasia of the lateral ventricles, mild hypoplasia of the cerebellar vermis and brainstem with wide communication between the fourth ventricle and the cisterna magna. Neurological examination revealed dyslalia, mild generalized hypotonia, ataxic gait, motor coordination and balance deficits, while the Wechsler Intelligence Scale for Children revealed the presence of mild intellectual disability. A clinical exome and neurodevelopmental multigenic analysis revealed two variants of the POLR3A gene in compound heterozygosity (c.1795 C > A and c.1289 + 3 A > G) previously described in the literature and a novel and not yet reported CACNA2D2 variant (c.2929 C > T).</p><p><strong>Conclusions: </strong>Beside the shared genetic and neuropsychological findings, the distinctive MRI and classical clinical signs of POLR3-related leukodystrophy have not been revealed in our case. This finding underscores the need to expand the diagnostic approach for POLR3A-related disorders, highlighting the significance of differentiating subtle clinical signs and promoting the use of genetic testing, especially in younger patients who may not yet display the typical clinical and MRI patterns. Further studies are necessary to shed light on different pathogenic mechanisms potentially responsible for the heterogeneous phenotype associated with POLR3-related disorders.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"191"},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302066","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":"The landscape of pediatric genetic white matter disorders at a tertiary referral hospital in Upper Egypt and the report of 31 novel variants.","authors":"Mahmoud M Noureldeen, Maha S Zaki, Karima Rafat, Mohamed S Abdel-Hamid, Aida M S Salem","doi":"10.1186/s13052-025-02031-6","DOIUrl":"10.1186/s13052-025-02031-6","url":null,"abstract":"<p><strong>Background: </strong>Leukodystrophies (LDs) and genetic leukoencephalopathies (GLEs) encompass the spectrum of genetic white matter disorders (GWMDs). Despite their clinical significance, limited studies have investigated GWMDs in Egypt. Therefore, this study aimed to characterize pediatric patients diagnosed with GWMDs in the Beni-Suef Governorate, Upper Egypt.</p><p><strong>Methods: </strong>We reviewed the records of patients diagnosed with GWMDs who presented over five years to the pediatric neurology clinic of a tertiary care hospital in Beni-Suef Governorate, Upper Egypt. The study included 142 patients aged < 18 years diagnosed with GWMD confirmed by brain imaging, metabolic, and/or molecular genetic testing. Patients were classified as LDs or GLEs per the 2015 Global Leukodystrophy Initiative Consortium (GLIA) criteria.</p><p><strong>Results: </strong>Fifty-six cases were identified to have LDs, while 86 were classified as GLEs. Metachromatic leukodystrophy (MLD) was the most common LD (13 patients), followed by megalencephalic leukoencephalopathy with subcortical cysts (MLC) (10 patients). The most common GLEs were lysosomal storage disorders (LSDs) (22 patients,) followed by Cockayne syndrome (11 patients), along with other miscellaneous disorders. The cumulative incidence of GWMDs in children under 18 was estimated at 10.8 cases per 100,000 population during the five-year study period. Thirty-one novel variants were identified, comprising 10 for LDs and 21 for GLEs. The mortality rate was 39.3% and 22.1% among patients with LDs and GLEs, respectively.</p><p><strong>Conclusions: </strong>This study presents the first cohort of GWMDs reported from the Beni-Suef Governorate, Upper Egypt. The study provides significant data regarding regional etiological patterns, clinical trajectories, and molecular profiles. Additionally, the study findings provide a foundational framework for establishing a national GWMD registry and inform future diagnostic and therapeutic strategies.</p>","PeriodicalId":14511,"journal":{"name":"Italian Journal of Pediatrics","volume":"51 1","pages":"187"},"PeriodicalIF":3.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293679","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}