Translational pediatrics最新文献

Background: Jordan syndrome is a rare neurodevelopmental disorder caused by mutations in the PPP2R5D gene. It is characterized by developmental delay, macrocephaly, hypotonia, epilepsy, and autism spectrum disorder. This study aims to enhance clinical recognition of the disease by presenting two genetically confirmed cases and a comprehensive literature review.

Case description: This study retrospectively analyzed two unrelated male patients diagnosed with Jordan syndrome, both carrying the heterozygous PPP2R5D variant c.598G>A (p.Glu200Lys), confirmed as de novo. Both patients exhibited global developmental delay, macrocephaly, dysmorphic facial features, and abnormal cranial magnetic resonance imaging (MRI) findings. One patient also presented with epilepsy and experienced unexplained recurrent fever for 8 months during infancy. Electroencephalogram (EEG) abnormalities persisted over long-term follow-up despite antiepileptic treatment. Genetic testing confirmed the absence of this variant in their parents, and the variant was not found in the gnomAD database. In silico predictions using PolyPhen-2 and AlphaFold indicated a deleterious effect. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant was classified as "pathogenic".

Conclusions: The c.598G>A (p.Glu200Lys) mutation is one of the most frequently reported pathogenic variants of PPP2R5D. The two cases reported here not only align with the known clinical spectrum of Jordan syndrome but also highlight a potentially novel phenotype of persistent unexplained fever in early infancy. Our literature review summarizes 213 reported cases and emphasizes the genotype-phenotype correlations, especially among patients with the c.598G>A (p.Glu200Lys) variant. Early diagnosis through genetic testing and multidisciplinary management is essential to optimize outcomes.

Background: Isolated fallopian tube torsion (IFTT) is an uncommon yet significant differential diagnosis in pediatric female patients presenting with acute abdominal pain. Delayed recognition may lead to tubal necrosis, necessitating salpingectomy and potentially compromising future fertility. Due to its low incidence and nonspecific clinical presentation, IFTT remains underdiagnosed in the pediatric population. This study aims to investigate the preoperative diagnosis and postoperative pathological conditions of IFTT patients.

Methods: A retrospective case series was conducted at Beijing Children's Hospital, Capital Medical University, between January 2020 and December 2024. Pediatric female patients under 18 years of age with intraoperatively confirmed IFTT were included. Data on clinical presentation, imaging findings, intraoperative observations, and histopathological results were reviewed.

Results: Eighteen patients (mean age: 12.19±1.58 years) met the inclusion criteria. Torsion occurred with equal frequency on the right and left sides (50% each). The predominant symptom was localized lower abdominal pain. Abdominal tenderness was noted in 72% of cases, and 28% presented with associated vomiting. Ultrasonography identified features suggestive of IFTT in 33% of cases, while computed tomography did not provide significant additional diagnostic value. All patients underwent laparoscopic exploration. Intraoperative findings included hydrosalpinx (28%), Müllerian cysts (44%), and para-tubal cysts (28%). Salpingectomy was performed in cases with irreversible ischemic injury.

Conclusions: Pediatric IFTT presents with nonspecific symptoms and poses a diagnostic challenge. Imaging modalities demonstrate limited sensitivity, highlighting the importance of early surgical evaluation. Laparoscopy enables prompt diagnosis and supports the possibility of fertility-preserving management. Enhanced clinical awareness of IFTT is essential among pediatric surgeons and gynecologists. Congenital or acquired tubal anomalies, such as cysts or hydrosalpinx, may contribute to the pathogenesis of torsion in this population.

Background: Autosomal dominant signal transducer and activator of transcription 3 (STAT3) mutations are broadly classified into loss-of-function (LOF) and gain-of-function (GOF) variants. LOF mutations in STAT3 are responsible for autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES), a rare primary immunodeficiency disorder. This condition is characterized by elevated serum immunoglobulin E (IgE) levels, chronic eczema, and recurrent respiratory tract infections. Current conventional management strategies include antimicrobial therapy, immunoglobulin replacement, and systematic airway clearance. However, there remains a lack of targeted therapies specifically for AD-HIES, leading to substantial morbidity and significantly compromised quality of life for affected patients. Omalizumab, a monoclonal anti-human IgE antibody, is approved for the treatment of asthma and chronic spontaneous urticaria, but is rarely used in AD-HIES. Relevant studies on the application of omalizumab in AD-HIES patients primarily focus on alleviating skin issues, with significant improvements reported in most cases, but rarely focus on alleviating the lung symptom. We report two cases in which both skin and lung symptoms improved through a combination of omalizumab and conventional treatment.

Case description: We report two cases of AD-HIES caused by STAT3 mutations, both complicated by pulmonary involvement. These two patients continued to experience frequent acute infections despite long-term antibiotic use, regular airway clearance, and other conventional treatments. We introduced omalizumab as an adjunct to their existing therapy. After 9 months of treatment, both their skin and lung symptoms were well controlled. The administration of omalizumab in combination with conventional therapy resulted in varying degrees of clinical improvement.

Conclusions: The combination of omalizumab with conventional therapy may contribute to improved pulmonary and dermatological symptoms in patients with AD-HIES resulting from STAT3 LOF mutations.

Background: The periorbital region is one of the most prominent areas for social interaction. Conventional open surgeries in this area often leave scars or cause aesthetic and functional issues owing to tissue tension. Endoscopic methods are increasingly being applied to unconventional surgical approaches in pediatric surgery. This study aimed to introduce a method of resecting pediatric periorbital masses using endoscopic assistance with hidden incisions within the hairline and to compare its outcomes with those of conventional open surgeries.

Methods: Clinical data were collected from 46 pediatric patients diagnosed with "periorbital masses" who underwent mass resection surgery in the Department of Neurosurgery, Beijing Children's Hospital, Capital Medical University, between August 31, 2023, and September 1, 2024. The data collected included sex, age, surgery and hospitalization duration, mass size, postoperative pathology results, and total hospitalization costs. Postoperative follow-up data included the presence of complications, recurrence, and adoption of anti-scar treatment measures. Statistical analysis and visualization were performed using SPSS 22.0 and GraphPad Prism 10, with statistical significance set at P<0.05.

Results: A total of 46 children diagnosed with periorbital masses were included in the study, consisting of 30 males and 16 females, aged 0-14 years (median age: 3 years). The median age of patients undergoing conventional open surgery was 4 years (1-6 years), while the median age of those receiving endoscopic-assisted surgery was 1 year (1-3 years), with the latter being significantly younger. No statistically significant differences were found between the two surgical approaches in terms of mass size, hospitalization duration, average hospitalization costs, nor postoperative complication rates. However, the average surgical duration was significantly longer with the new technique. No recurrence was observed in any patient during the follow-up period. Notably, none of the 17 patients who underwent the new surgical technique required postoperative anti-scar treatment, compared to the higher rate of anti-scar treatment in the conventional surgery group.

Conclusions: Endoscopic resection of pediatric periorbital masses using a novel subcutaneous operative channel is a minimally invasive, safe, effective, cost-effective, and yields superior cosmetic outcomes, presenting a promising clinical application.

Background: Parenting plays a crucial role in the development and management of children with attention deficit hyperactivity disorder (ADHD). Understanding how different parenting style dimensions interact can inform family-based interventions. This study aimed to investigate the associations between parental overprotection, rejection, and emotional warmth in parents of children diagnosed with ADHD and to compare these associations between mothers and fathers.

Methods: A cross-sectional study was conducted involving 31 families of children aged 7 to 9 years diagnosed with ADHD. Children completed the Egna Minnen Beträffande Uppfostran-Short Form (S-EMBU) to evaluate their perceptions of parental behaviors across three dimensions: rejection, overprotection, and emotional warmth. Correlation analyses were performed using SPSS version 20.0.

Results: Strong positive correlations were found between parental rejection and overprotection in both mothers (r=0.822, P<0.001) and fathers (r=0.800, P<0.001). Emotional warmth showed weak negative correlations with both rejection and overprotection. These results indicate that rejecting and overprotective parenting behaviors tend to co-occur in parents of children with ADHD.

Conclusions: Parental rejection and overprotection show strong positive associations in both mothers and fathers of children with ADHD, suggesting these parenting styles may co-occur rather than being independent dimensions. These preliminary findings highlight the complex relationships between different parenting approaches in families of children with ADHD.

Background: Infantile epileptic spasms syndrome (IESS) is an age-related developmental and epileptic encephalopathy. Adrenocorticotropic hormone (ACTH), one of the first-line treatment, has its efficacy influenced by multiple factors. This study aimed to investigate and analyze clinical variables (pre-treatment clinical data, serum and urine routine test) in children with IESS to predict outcomes after the first ACTH treatment. Furthermore, the potential impact of underlying factors on ACTH efficacy was assessed.

Methods: A total of 186 children who received ACTH treatment for the first time in the Pediatric Department of The First Medical Center of the Chinese PLA General Hospital from January 2018 to June 2023 were retrospectively evaluated. They were divided into the responsive group and the non-responsive group according to the clinical outcomes after treatment. The clinical data of the two groups were compared, followed by logistic regression analysis to evaluate the relationship between the factors and ACTH treatment outcome.

Results: The lead time between the first spasm onset and ACTH treatment initiation was significantly shorter in the responsive group compared with the non-responsive group. Additionally, more patients experienced epileptic spasms after the age of 3 months and responded significantly better to ACTH treatment than those whose spasms began within the first 3 months. Compared to children with IESS of unknown etiology, patients with congenital genetic abnormalities without structural abnormalities were less likely to have a short-term response to ACTH treatment. Despite no significant differences in serum sodium, potassium, calcium, and chloride levels between the two groups, pre-treatment serum inorganic phosphate levels were correlated with ACTH efficacy. The responsive group had significantly higher pre-treatment urinary pH levels.

Conclusions: IESS patients should receive first-line treatment immediately after spasm onset. The age of epileptic spasms onset and its etiology may help predict the efficacy of ACTH treatment. Serum inorganic phosphate levels and urinary pH levels seem to play an important role in the treatment of IESS with ACTH, and they may have indicative significance for precision treatment.

Background: Optimizing transfusion regimens is crucial for children with transfusion-dependent thalassemia (TDT). This study aimed to identify the determinants of intertransfusion intervals to address this need.

Methods: This single-center retrospective observational study included 21 pediatric β-thalassemia patients with 392 transfusions. Transfusions were grouped by median interval (18 days). The associations between intertransfusion intervals and demographics, genotype, red blood cells (RBC) product characteristics, as well as transfusion adequacy were analyzed using univariate tests and correlation analysis. Binary logistic regression was used to identify the independent determinants of intertransfusion intervals, and then multivariable linear regression was constructed to evaluate the factors influencing hemoglobin levels before the subsequent transfusion.

Results: Genotype severity [major vs. minor, odds ratio (OR) =0.397, P=0.03] and RBC product type [leukocyte-reduced RBC (LRBC) vs. washed RBC (WRBC), OR =0.378, P=0.007] independently influenced intertransfusion intervals. Age and weight correlated negatively with intertransfusion intervals (r =-0.341 and -0.298, P<0.001). Patients with a major genotype exhibited a markedly decreased of 8.428 g/L (P<0.001) in the hemoglobin level before the subsequent transfusion, while the intermediate genotype showed a moderate reduction of 5.534 g/L (P=0.01), relative to the minor genotype reference. LRBC transfusions were associated with a significant hemoglobin advantage, demonstrating a 2.681 g/L elevation (P=0.049) compared to WRBC transfusions, administered as 1-unit protocols. Adverse reactions occurred in 5/21 patients (23.8%), which included febrile reactions and alloimmunization.

Conclusions: Genotype severity and RBC product type significantly affect intertransfusion intervals in pediatric TDT. Personalized strategies considering these factors may optimize transfusion efficacy and reduce complications.

Background: Neonatal respiratory distress syndrome (NRDS) is a leading cause of neonatal respiratory failure and mortality. This study investigated risk factors for intensive care unit (ICU) length of stay in newborns with NRDS.

Methods: The data were collected from the MIMIC-III database. Baseline characteristics were recorded. Machine learning methods were used to identify key factors associated with ICU stay length. The nonlinear associations of hemoglobin and base excess (BE) with ICU stay length were assessed using generalized additive model (GAM) analysis and threshold effect analysis. Mediation analysis explored the relationship between hemoglobin, BE, and length of ICU stay.

Results: We enrolled 1,241 NRDS-diagnosed newborn infants. Four key variables (height, weight, hemoglobin, and BE) were correlated with the length of ICU stay. Specifically, hemoglobin levels (≥12.1 g/dL) and BE (≥-8.3 mmol/L) were negatively correlated with ICU stay length. Hemoglobin was an independent predictor for shorter ICU stay (β=-0.503, 95% CI: -0.958 to -0.049) (P<0.05), and its level was positively associated with BE (P<0.05). Mediation analysis revealed that BE partially mediated the relationship between hemoglobin and ICU stay length.

Conclusions: Hemoglobin level was a crucial independent predictor for ICU stay duration in NRDS patients, with BE as a mediator. These findings highlight the importance of maintaining adequate hemoglobin levels to improve NRDS outcomes.

Background: Extrahepatic portal vein obstruction (EHPVO) is a leading cause of pediatric portal hypertension. While invasive portography remains the diagnostic gold standard, its risks highlight the need for non-invasive alternatives. This study aims to integrate ultrasound imaging features and serological markers to establish a machine learning model for noninvasive, simplified preoperative assessment of the portal system in pediatric patients with EHPVO. The model will serve as a reference for selecting optimal surgical strategies.

Methods: A total of 103 pediatric EHPVO patients who underwent surgery were enrolled, including 81 Rex shunt and 22 Warren shunt cases. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm identified potential predictors. Five machine learning algorithms were employed for modeling. Model performance was evaluated through internal validation and external validation.

Results: Baseline characteristics showed no significant differences between training and validation sets. LASSO-selected features were used to construct five prediction models. The extreme gradient boosting (XGBoost) model outperformed the others. It achieved an area under the receiver operating characteristic curve (AUC) of 0.90 [95% confidence interval (CI): 0.79-0.99] on the training set and 0.75 (95% CI: 0.54-0.97) on the validation set. An online platform (https://rexshunt.shinyapps.io/rexorwarren/) was subsequently developed based on this optimal model.

Conclusions: This study established a predictive model combining serological markers and ultrasound parameters to preoperatively assess portal venous anatomy in pediatric EHPVO. The online tool provides a noninvasive, user-friendly solution to guide surgical strategy selection for children with EHPVO.

Background: Hemiplegic migraine (HM) is a rare monogenic subtype of migraine characterized by a broad spectrum of symptoms, ranging from transient hemiplegic episodes to recurrent coma. Imaging documentation of cerebral vasospasm during acute HM attacks is exceedingly rare. We present a pediatric case of familial HM (FHM) with cerebral vasospasm and acute encephalopathy caused by an ATP1A2 gene variant to enhance clinical recognition of this condition.

Case description: An 11-year-old Asian female with a 2-year history of recurrent HM presented with fever, headache, altered consciousness, and right-sided weakness for 48 hours. The current acute episode occurred without identifiable triggers and was characterized by fever, prolonged headache, acute encephalopathy, and persistent hemiplegia. Acute-phase magnetic resonance imaging revealed left cerebral cortical swelling with mild diffusion restriction. Magnetic resonance angiography demonstrated dynamic cerebral vasospasm, with spontaneous resolution observed on follow-up imaging. A heterozygous c.2464G>A (p.Glu822Lys) missense variant in the ATP1A2 gene was identified; this variant was inherited from her mother, who has a history of recurrent headaches.

Conclusions: This report describes a unique case of internal carotid artery vasospasm occurring in HM, which, to our knowledge, has not been previously reported in the literature. Investigating alterations in the cerebrovascular system contributes significantly to understanding the clinical manifestations and underlying mechanisms of HM.