OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

OBJECTIVE: To summarize the clinical and genetic characteristics of children with Silver-Russell syndrome (SRS) and improve the recognition of this disease. METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of 29 children with SRS diagnosed at the Children's Hospital Affiliated to Zhengzhou University between March 2016 and June 2025. RESULTS: The 29 children had included 18 boys and 11 girls, with the age ranging from 2 months to 16 years. Their primary clinical manifestations included postnatal growth retardation (100%), small for gestational age (SGA) (100%), characteristic facial features (90%), limb asymmetry (83%), feeding difficulties (76%), ulnar deviation of the fifth finger (69%), body mass index (BMI) of < -2 SD (62%), and abnormal bone age (55%), including 15 cases with delayed bone age for an average of 1.5 years and 1 case with advanced bone age for 2.5 years. Additional manifestations included abnormal sexual development in 11 cases (38%), dental malocclusion in 11 cases (38%), allergic diseases in 10 cases (34%), cardiac diseases in 9 cases (31%), skeletal abnormalities in 7 cases (24%), renal hypoplasia in 5 cases (17%), and abnormal cranial MRI findings in 5 cases (17%). Twenty children were treated with recombinant human growth hormone (rhGH) at a dose of 0.1 ~ 0.15 U/(kg.d). Among them, 7 cases achieved annual height increase of ≥ 10 cm, 11 cases achieved annual height increase of ≥ 5 ~ 9 cm, and 2 cases achieved annual height increase < 5 cm. Twenty three children exhibited hypomethylation of imprinted genes in the chromosome region of 11p15, 4 presented maternal uniparental disomy of chromosome 7 [UPD(7)mat], and 2 had harbored nonsense variants of the HMGA2 gene. CONCLUSION SRS patients may present with diverse clinical manifestations including postnatal growth retardation, SGA, characteristic facial features, limb asymmetry, feeding difficulties, and ulnar deviation of the fifth finger. Most patients may exhibit abnormal methylation in the 11p15 region. rhGH therapy can improve the height of these patients.
Humans ; Silver-Russell Syndrome/diagnosis* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

Drug-induced sleep endoscopy (DISE) is used for directly visualizing sites of obstruction among patients with obstructive sleep apnea (OSA). Owing to the scarcity of data, there is still no consensus on the anesthetic regimen for conducting pediatric DISE.

This paper presents a 5-year-old patient who underwent DISE using an opioid-sparing regimen with dexmedetomidine and propofol infusion.

Simultaneous dexmedetomidine and propofol infusion is a promising opioid-sparing regimen for pediatric DISE.

Human ; Male ; Child Preschool: 2-5 Yrs Old ; Endoscopy ; Propofol ; Dexmedetomidine ; Sleep Apnea, Obstructive ; Anesthetics ; Apnea ; Consensus ; Paper ; Patients ; Pharmaceutical Preparations ; Research Report ; Sleep ; Sleep Apnea Syndromes ; World Health Organization

OBJECTIVE: This study described bronchiectasis profiles at the Philippine Children’s Medical Center (2021-2023). MATERIALS AND METHODS: A retrospective chart review at PCMC analyzed the demographic profile, imaging, management and outcome of patients with bronchiectasis enrolled in the Chronic Lung Disease Program from 2021-2023. Results: Twenty seven patients were included in this study. Most patients were diagnosed after the age of six and showed female predominance. The most common symptom at the time of diagnosis was chronic cough (81.5%) with pulmonary tuberculosis (51.9%) as the most common etiology. All patients were treated with cyclic azithromycin. Pseudomonas aeruginosa was the prevalent microorganism isolated in the sputum and tracheal aspirate samples of the patients (56.5%). Conclusion Patients with bronchiectasis were more commonly diagnosed in children past age of six with more prevalence in females. The most common symptom was chronic cough followed by fever, dyspnea and weight loss. Pulmonary tuberculosis and recurrent respiratory infections were noted to be the most common etiology with the left lower lobe most affected in HRCT. The most common phenotype seen was cystic, which is irreversible and a sign of progressive bronchiectasis, which may point to a late diagnosis. This emphasizes the need for physicians to have a high index of suspicion in patients with chronic or recurrent respiratory symptoms. All patients were treated with an oral macrolide with 25-31% of patients with decreased and/or absent symptoms. Pseudomonas aeruginosa was the prevalent microorganism isolated in the sputum and tracheal aspirate samples of the patients, which should be taken into account when treating for exacerbation.
Human ; Male,Female ; Infant newborn: First 28 days after birth ; Infant: 1-23 months ; Child Preschool: 2-5 yrs old ; Child: 6-12 yrs old ; Bronchiectasis ; Patients ; Tuberculosis ; Infections

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is a common mental disorder in children. It is unclear how nutrition and dietary components relate to ADHD. Some studies suggest that children with ADHD have lower serum levels of vitamin D than healthy controls. In the current study, the effects of Vitamin D supplementation on ADHD were reviewed and analyzed using available literature. MATERIALS AND METHODS: A meta-analysis and systematic review were performed. Children less than 18 years old diagnosed with ADHD given Vitamin D supplementation or placebo were included. A search was performed in PubMed/MEDLINE, EMBASE, Scopus, Cochrane, and Google Scholar databases from inception to August 2024 using the MeSH keywords: "Vitamin D" AND (ADHD OR Attention Deficit Hyperactivity Disorder) AND (children OR pediatric OR adolescents) AND randomized controlled trial. Standardized Mean Difference (SMD) was used as an effect measure and pooled using random effects meta-analysis. RESULTS: The pooled SMS showed significantly lower ADHD scores (SMD=-0.59, 95%CI=-1.06 to -0.11, p=0.01), lower inattentive scores (SMD=-0.61, 95%CI=-1.00 to -0.23, p=0.002), and lower hyperactivity scores (SMD=-0.64, 95%CI=-1.08 to -0.20, p=0.004) in children given Vitamin D supplementation. The adverse events reported were minor only and did not vary significantly between intervention and control groups. CONCLUSION Vitamin D treatment as an adjuvant to methylphenidate alleviated ADHD symptoms without significant adverse effects, correlating with enhanced vitamin D levels. Given the robust evidence and well-structured randomized controlled trials, we strongly advocate for the integration of vitamin D supplementation with ADHD treatment.
Human ; Male,Female ; Adolescent: 13-18 yrs old ; Child Preschool: 2-5 yrs old ; Child: 6-12 yrs old ; Vitamin D ; meta-analysis ; systematic review

OBJECTIVE: To investigate the application value of pediatric sepsis-induced coagulation (pSIC) score and mean platelet volume/platelet count (MPV/PLT) ratio in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. METHODS: A retrospective cohort study was conducted, selecting 112 children with sepsis (sepsis group) admitted to pediatric intensive care unit (PICU) of Liaocheng Second People's Hospital from January 2020 to December 2023 as the study objects, and 50 children without sepsis admitted to the pediatric surgery department of our hospital during the same period for elective surgery due to inguinal hernia as the control (control group). The children with sepsis were divided into two groups according to the pediatric critical case score (PCIS). The children with PCIS score of ≤ 80 were classified as critically ill group, and those with PCIS score of > 80 was classified as non-critically ill group. pSIC score, coagulation indicators [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB)], and platelet related indicators (PLT, MPV, and MPV/PLT ratio) were collected. Pearson correlation method was used to analyze the correlation between pSIC score and MPV/PLT ratio as well as their correlation with coagulation indicators. Multivariate Logistic regression analysis was used to screen the independent risk factors for pediatric sepsis and critical pediatric sepsis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the application value of the above independent risk factors on the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. RESULTS: 112 children with sepsis and 50 children without sepsis were enrolled in the final analysis. pSIC score, PT, INR, APTT, FIB, MPV, and MPV/PLT ratio in the sepsis group were significantly higher than those in the control group [pSIC score: 0.93±0.10 vs. 0.06±0.03, PT (s): 14.76±0.38 vs. 12.23±0.15, INR: 1.26±0.03 vs. 1.06±0.01, APTT (s): 40.08±0.94 vs. 32.47±0.54, FIB (g/L): 3.51±0.11 vs. 2.31±0.06, MPV (fL): 8.86±0.14 vs. 7.62±0.11, MPV/PLT ratio: 0.037±0.003 vs. 0.022±0.001, all P < 0.01], and PLT was slightly lower than that in the control group (×10⁹/L: 306.00±11.01 vs. 345.90±10.57, P > 0.05). Among 112 children with sepsis, 46 were critically ill and 66 were non-critically ill. pSIC score, PT, INR, APTT, MPV, and MPV/PLT ratio in the critically ill group were significantly higher than those in the non-critically ill group [pSIC score: 1.74±0.17 vs. 0.36±0.07, PT (s): 16.55±0.80 vs. 13.52±0.23, INR: 1.39±0.07 vs. 1.17±0.02, APTT (s): 43.83±1.72 vs. 37.77±0.95, MPV (fL): 9.31±0.23 vs. 8.55±0.16, MPV/PLT ratio: 0.051±0.006 vs. 0.027±0.001, all P < 0.05], PLT was significantly lower than that in the non-critically ill group (×10⁹/L: 260.50±18.89 vs. 337.70±11.90, P < 0.01), and FIB was slightly lower than that in the non-critically ill group (g/L: 3.28±0.19 vs. 3.67±0.14, P > 0.05). Correlation analysis showed that pSIC score was significantly positively correlated with MPV/PLT ratio and coagulation indicators including PT, APTT and INR in pediatric sepsis (r value was 0.583, 0.571, 0.296 and 0.518, respectively, all P < 0.01), and MPV/PLT ratio was also significantly positively correlated with PT, APTT and INR (r value was 0.300, 0.203 and 0.307, respectively, all P < 0.05). Multivariate Logistic regression analysis showed that pSIC score and MPV/PLT ratio were independent risk factors for pediatric sepsis and critical pediatric sepsis [pediatric sepsis: odds ratio (OR) and 95% confidence interval (95%CI) for pSIC score was 14.117 (4.190-47.555), and the OR value and 95%CI for MPV/PLT ratio was 1.128 (1.059-1.202), both P < 0.01; critical pediatric sepsis: the OR value and 95%CI for pSIC score was 8.142 (3.672-18.050), and the OR value and 95%CI for MPV/PLT ratio was 1.068 (1.028-1.109), all P < 0.01]. ROC curve analysis showed that pSIC score and MPV/PLT ratio had certain application value in the diagnosis of pediatric sepsis [area under the ROC curve (AUC) and 95%CI was 0.754 (0.700-0.808) and 0.720 (0.643-0.798), respectively] and the determination of critical pediatric sepsis [AUC and 95%CI was 0.849 (0.778-0.919) and 0.731 (0.632-0.830)], and the combined AUC of the two indictors was 0.815 (95%CI was 0.751-0.879) and 0.872 (95%CI was 0.806-0.938), respectively. CONCLUSIONS pSIC score and MPV/PLT ratio have potential application value in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis, and the combined application of both is more valuable.
Humans ; Sepsis/complications* ; Platelet Count ; Mean Platelet Volume ; Retrospective Studies ; Child ; Blood Coagulation Disorders/diagnosis* ; Intensive Care Units, Pediatric ; Male ; Female ; Partial Thromboplastin Time ; Child, Preschool ; Blood Coagulation ; International Normalized Ratio ; Infant