Abstract Objective To analyze the clinical characteristics and prognosis of pediatric intracranial malignant germ cell tumors (iMGCTs) in a single institution. Methods A retrospective analysis was conducted on the clinical data of pediatric primary iMGCTs admitted to the Medical Oncology Department, Beijing Children’ s Hospital from May 2017 to December 2024. The clinical characteristics and prognosis were summarized. Results A total of 36 patients were enrolled. The time interval from symptom onset to diagnosis was 0.2 to 40 months. Based on histopathology and tumor markers, 9 cases (25.0%) were diagnosed as germinomas, 26 cases (72.2%) were non-germinomatous germ cell tumors (NGGCT), and one was unclassifiable. All patients received comprehensive treatment including chemotherapy, radiotherapy, and surgery under the multidisciplinary treatment (MDT) model. The 3-year and 5-year overall survival (OS) rates of germinomas were both 100%, and the 3-year and 5-year event-free survival (EFS) rates were 100% and 88.9%, respectively. For NGGCT cases, the 3-year and 5-year OS rates were 95.8% and 91.3%, respectively, and the 3-year and 5-year EFS rates were both 69.2%. Patients of NGGCTs who underwent surgical resection of the tumor during first-line treatment had significantly higher EFS than those who did not (88.2% vs 33.3%, P < 0.05). Among the survivors, 14 cases (38.9%) had endocrine abnormalities. One patient of NGGCT developed a second malignance (rhabdomyosarcoma) 2.5 years after treatment. Conclusion Pediatric iMGCTs have diverse clinical manifestations, requiring early identification and timely diagnosis. Even with multidisciplinary treatment, the EFS of NGGCTs remains suboptimal. Pathological components containing choriocarcinoma and absence of surgical resection during first-line therapy are poor prognostic factors, highlighting the potential importance of surgery in NGGCTs management and enhancing chemotherapy intensity for high-risk patients.​The treatment of iMGCTs should aim to minimize side effects while striving for long-term survival.

Objective To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor(eMRT)in children,and to provide a reference for the clinical treatment of this disease.Methods A retrospective analysis was performed on the clinical data of children with newly diagnosed eMRT who were admitted and treated in the Department of Pediatric Oncology,Beijing Children's Hospital Affiliated to Capital Medical University,from March 2009 to December 2024.The clinical characteristics were summarized,and survival analysis and prognostic risk factor analysis were conducted.Results A total of 43 children with eMRT were included in this study,the median age at diagnosis of all patients was 20 months(range:2-138 months).Among them,24 cases were malignant renal rhabdoid tumors and 19 cases were extracranial,extra-renal rhabdoid tumors.Of the 43 children,23 cases(53.5%)were complicated with distant metastasis.Twen-ty-nine(67.4%)underwent primary tumor resection.Among the children,24(55.8%)underwent gross total resection(GTR),5(11.6%)partial resection,and 14(32.6%)biopsy only.Their 3-year overall survival(OS)rates were 40.8%,35.3%,and 33.3%,respectively(P=0.711).Chemotherapy was administered to 42 children(97.7%);among those who were ineligible for GTR and had poor chemotherapy sensitivity,the 3-year OS rate was significantly lower than that of chemotherapy-sensitive children(28.6%vs.58.2%,P=0.041).Radiotherapy was given to 15 children(34.9%),with the 3-year OS rate in the radiotherapy group being higher than that in the non-radiotherapy group(69.1%vs.32.9%,P=0.026).The 3-year event-free survival(EFS)and OS rates of all 43 children were 31.4%and 44.3%,respectively.Multivariate Cox regres-sion analysis showed that a diagnostic age＜12 months was significantly associated with a higher risk of death(hazard ratio[HR]=3.7,95%confidence interval[CI]:1.2-11.1,P=0.020).Conclusions Children with eMRT have an overall poor prognosis.A diagnostic age＜12 months is an independent risk factor for higher mortality in these children.Further large-scale,long-term follow-up studies are needed to explore the prognostic factors of this disease.

The SMARCA4 gene encodes a key ATPase subunit of the SWI/SNF (BAF) chromatin-remodeling complex, which plays an essential role in regulating transcription and cellular differentiation. Loss-of-function alterations of SMARCA4 are common in various human cancers, including sarcomas; however, rare SMARCA4 fusion events, presumably resulting in gain of function, have also been reported. We present two pediatric soft-tissue sarcomas harboring a novel, recurrent in-frame fusion between SMARCA4 and VEZF1 (Vascular Endothelial Zinc Finger 1), a transcription factor important for vascular development and angiogenesis. The predicted fusion protein contains the N-terminal QLQ protein interaction domain of SMARCA4 and preserves most of VEZF1's C2H2 zinc-finger DNA-binding domains. Interestingly, another component of the BAF complex, SS18, has also been reported to be fused to VEZF1 in uterine sarcoma. We propose that fusion of BAF complex components to VEZF1 leads to aberrant recruitment of chromatin-remodeling activity to VEZF1 target loci, resulting in altered chromatin architecture, dysregulated VEZF1-dependent transcription, and tumorigenesis.

We present a case of a 6-month-old boy who was diagnosed with Peutz-Jeghers polyps, intestine fusiform mesenchymal tumor, Wilms tumor, and Ir type pleuropulmonary blastoma (PPB) successively, with mosaic DICER1 RNase IIIb hotspot mutation: c.5113G>A p.E1705K. The patient underwent surgeries to resect the intestine polyps, intestine tumor, Wilms tumor, nephroblastomatosis, and PPB, combined with chemotherapy aimed at Wilms tumor and PPB. Diseases were stable at follow-up 27 months since the initial diagnosis.

ABSTRACT Objective: To evaluate diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) for the prenatal differentiation of fetal adrenal neuroblastoma (NB) from benign masses. Methods: This retrospective study analyzed prenatal magnetic resonance imaging/DWI data from 54 pregnant women (59 adrenal masses) with a suspected solid adrenal mass on ultrasound. Cases with severe malformations or poor image quality were excluded. The minimum ADC (ADC min ), mean ADC (ADC mean ), and relative ADC (rADC) values within the tumor solid components were measured. Group comparisons and receiver operating characteristic (ROC) curve analysis were performed to assess the diagnostic performance. Results: Eighteen masses (30.5%) were classified as NB, while the remaining 41 (69.5%) were benign, including sequestration, hematoma, and teratoma. The NB group showed significantly greater gestational age at detection (mean age, 35 weeks), higher right adrenal prevalence (66.7%), and larger maximum diameters (3.6 cm vs. 2.4 cm; P < 0.01) compared to the non-NB group. The ADC min , ADC mean , and rADC were significantly lower in the NB group ( P < 0.001). ROC analysis identified ADC min as the optimal diagnostic parameter (area under the curve = 0.981). An ADC min threshold of 1382 μm²/s yielded 97.56% sensitivity and 100% specificity. Conclusion: These findings indicate that the quantitative DWI parameter ADC min can reliably differentiate fetal adrenal NB from benign lesions prenatally. Its high sensitivity and specificity may provide an objective basis for clinical decisions and optimized perinatal management.

Basal-like breast cancer (BLBC), overlapping with the subgroup of estrogen receptor (ER), progesterone receptor (PR), and HER2 triple-negative breast cancer, has the worst prognosis and limited therapeutics. The XPO1 gene encodes nuclear export protein 1, a promising anticancer target which mediates nucleus-cytoplasm transport of nuclear export signal containing proteins such as tumor suppressor RB1 and some RNAs. Despite drugs targeting XPO1 are used in clinical, the regulation of XPO1 expression and functional mechanism is poorly understood, especially in BLBC. This study finds that KLF5 is a transcription factor of XPO1, which increases RB1 nuclear export and cell proliferation in BLBC cells. Furthermore, XPO1 interacts with the RNA-binding protein PTBP1 to export FOXO1 mRNA to cytoplasm and thus activates the FOXO1-KLF5 axis as a feedback. This work demonstrates that XPO1 inhibitor KPT-330 in combination with CDK4/6 inhibitor additively suppressed BLBC tumor growth in vivo. These results reveal a novel positive feedback regulation loop between KLF5 and XPO1 and provide a novel treatment strategy for BLBC.

Biliary atresia (BA) is a severe neonatal disease characterized by obstruction of the biliary system and hepatic fibrosis. Epithelial-mesenchymal transition (EMT) occurs during the development of liver fibrosis in BA. However, the molecular mechanism that promotes elevated MMP7 expression and mediates the EMT process remains unknown. SULT2B1 has been shown to be involved in the intrahepatocellular EMT process, but its role in BA remains unknown. In this study, we found that SULT2B1 was overexpressed in BA livers. The increased expression of SULT2B1 exhibited a high association with the severity of fibrosis and poor prognosis in BA, and it was significantly correlated with the MMP7-mediated EMT in cholangiocytes. Further study showed that the abnormal high expression of SULT2B1 was located in cholangiocytes in BA, which was consistent with the pattern of MMP7. In vitro, upon the treatment of TGF-β1, SULT2B1 was overexpressed and promoted the EMT process via the Wnt/β-catenin/MMP7 pathway in a human intrahepatic bile duct epithelial cell line. Silencing of SULT2B1 expression blocked Wnt/β-catenin/MMP7-mediated cholangiocyte EMT. SULT2B1 was overexpressed in BA livers and correlated with fibrosis severity and poor prognosis. Its expression was associated with MMP7-mediated EMT in cholangiocytes, with overexpression localized similarly to MMP7. TGF-β1 induced SULT2B1 overexpression, activating the Wnt/β-catenin/MMP7 pathway to promote EMT, while SULT2B1 silencing inhibited this process. Inhibition of the SULT2B1/Wnt/β-catenin/MMP7 axis may represent a potential therapeutic strategy for BA.

Background:Pleuropulmonary blastoma (PPB) is a rare and highly aggressive malignant tumor of the lung or pleura, primarily affecting children and closely associated with DICER1 gene mutations. Patients with type II and III PPB are prone to distant metastasis, with the central nervous system (CNS) being the most common site of metastasis, leading to a poor prognosis. Case Description:This article provides a detailed account of the clinical manifestations, diagnostic processes, treatment plans, and follow-up outcomes of three children diagnosed with PPB accompanied by brain metastasis. Through the collaborative diagnosis and treatment by a multidisciplinary team, all three patients are currently in remission. As part of the diagnostic and treatment process, genetic testing was performed on two of the patients, revealing a pathogenic mutation in the DICER1 gene in one of them. Conclusions:Although the optimal treatment regimen for CNS metastasis in PPB remains unclear, combined treatment approaches offer new possibilities. In particular, brain computed tomography (CT) or magnetic resonance imaging (MRI) scans should be conducted every 3 months following the diagnosis of PPB to facilitate early detection of brain metastasis. Additionally, diagnosing PPB brain metastasis is challenging, and integrating patient history with genetic testing results plays a crucial role in distinguishing between primary intracranial tumors and PPB intracranial metastasis.

BACKGROUND AND OBJECTIVES:Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children.METHODS:Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification.RESULTS:Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy).DISCUSSION:OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Background:FUS-TFCP2 gene fusion is a recently identified and highly distinct molecular subtype of spindle cell/sclerosing rhabdomyosarcoma (RMS), with fewer than 40 cases being reported to date. Due to its low incidence, clinical studies on this subtype are limited. Here, we report a new case of this rare entity to describe and summarize its unique clinical characteristics and treatment process, aiming to emphasize the importance of molecular testing for spindle cell/sclerosing RMS and increase the understanding of this subtype. By summarizing and comparing with previous reports on RMS with the EWSR1/FUS-TFCP2 fusion mutation, we hope to make some new hints for its management.Case Description:In this report, we describe a rare case of spindle cell/sclerosing RMS in a 13-year-old boy, who had a massive destructive lesion involving the mandible. Next-generation sequencing of tumor tissue revealing a FUS-TFCP2 fusion. The tumor was extremely aggressive and showed resistance to polychemotherapy, after 4 cycles of multi drug combined chemotherapy, the primary tumor still continued to grow, and suspicious chest metastasis occurred. Even after aggressive total resection of the primary tumor and postoperative chemotherapy, systemic metastasis to the vertebra and chest could not be prevented yet, ultimately with a fatal outcome within 6 months. We additionally summarize 37 cases of RMS with the EWSR1/FUS-TFCP2 fusion mutation reported in the literature. This subtype was found to be almost exclusively primary in bone and histologically showed a common origin of epithelium and muscle. The high aggressiveness made the conventional standard chemoradiotherapy ineffective. Because most tumors of this subtype express ALK protein, ALK inhibitors seem to be a new target for its therapy.Conclusions:Spindle cell/sclerosing RMS with FUS-TFCP2 fusion has its unique clinical characteristics and progression. It shows a marked skeletal predilection and an aggressive clinical course, typically resistant to traditional standard treatments for RMS. Therefore, molecular detection is crucial in managing this subtype. Once the diagnosis is clear, a more aggressive treatment plan is needed. In addition, almost all cases were found to have a positive expression of ALK. So ALK inhibitors can be a choice of targeted therapy.

Background: Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients. Methods: A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed. Results: The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy. Conclusions: In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

ABSTRACTIn China, 45% of adolescents with obesity develop fatty liver disease, a condition that increases the long-term risk of developing cirrhosis and liver cancer. Although the factors triggering nonalcoholic fatty liver disease (NAFLD) vary in children, the composition of intestinal microflora has been found to play an increasingly important role. However, evidence is limited on the prevalence of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in Chinese children. Therefore, this study aimed to evaluate the fecal microbiome of Chinese children with NAFLD and further analyze the potential of flora in regulating NAFLD-related symptoms and metabolic functions. Specifically, the study applied a 16S rRNA and metagenomic sequencing to the fecal samples of pediatric patients with NAFLD, NASH, and NAFL, as well as healthy controls, to explore the correlation among NAFLD-related indexes, metabolic pathways, and gut flora. The findings showed that some fecal microbiota had a negative correlation with body mass index, and various NAFLD-related bacteria, including Lachnoclostridium, Escherichia-Shigella, and Faecalibacterium prausnitzii, were detected. Consequently, the study concluded that the variation in gut microbiota might be more important in improving NAFLD/NASH compared with single species, providing a microbiota diagnostic profile of NAFLD/NASH.IMPORTANCEThis study aims to characterize the gut microbiota in Chinese children with nonalcoholic fatty liver disease (NAFLD) through 16S rRNA and metagenomic sequencing. The results highlight the association between fecal microbiota and NAFLD in Chinese children, demonstrating distinct characteristics compared to adults and children from other countries. Based on the sequencing data from our cohort’s fecal samples, we propose a microbiota model with a high area under the curve for distinguishing between NAFLD and healthy individuals. Furthermore, our follow-up study reveals that changes in the relative abundance of microbial biomarkers in this model are consistent with variations in patients’ body mass index. These findings suggest the potential utility of the microbiota model and microbial biomarkers for diagnosing and treating NAFLD in children.

Background:Inflammatory myofibroblastic tumors (IMTs) are a spectrum of tumors that range in morphology and biological behavior from benign, intermediate, to apparently malignant and epithelioid inflammatory myofibroblastic sarcoma (EIMS) is one of the malignant subtypes. This study tried to provide experience and new ideas for treating this rare disease.Methods:This study retrospectively analyzed and followed up 12 children with EIMS admitted to Beijing Children's Hospital, Baoding Children's Hospital, and Children's Hospital of Chongqing Medical University from August 2016 to May 2022.Results:Of the 12 children, 7 were male and 5 were female, with a median age of 74.50 [interquartile range (IQR), 61.50-90.00] months. Of these patients, eight had a single lesion and four had multiple lesions. The maximum diameter of the single tumor foci was 19.30 cm, the full meridian of the multiple tumor foci target lesions was 32.67 cm, and the median maximum tumor size was 11.99 (IQR, 7.80-15.70) cm. The site of disease was the abdominopelvic cavity in eight cases, the thoracic cavity in two cases, the maxillofacial region in one case, and the larynx in one case. The clinical manifestations were predominantly elevated body temperature (n=8). There was one case of ROS1 fusion mutation and nine cases of ALK fusion mutation. Of the 12 children, 6 were biopsied at the initial diagnosis and 6 were surgically treated. Follow-up treatment included preoperative neoadjuvant chemotherapy (n=4), peritoneal thermal perfusion therapy (n=2), targeted therapy (n=3), postoperative chemotherapy (n=5), and radiotherapy (n=3). The follow-up time was 14.50 (IQR, 10.50-31.50) months, with eight cases of tumor-free survival, two cases of death, and two cases of loss of follow-up.Conclusions:EIMS in children is extremely rare and clinically aggressive. The clinical presentation is nonspecific, and the initial diagnosis of the tumor is often large. Mutations in the ALK gene are common in EIMS. Surgery is the mainstay of EIMS treatment, and patients benefit from a multidisciplinary combination that includes targeted therapies, with long-term prognosis remaining subject to ongoing follow-up.

Background This study aims to summarize the clinical features and prognoses of INI1-deficient tumors in children. It further aims to analyze the high-risk factors affecting INI1-deficient tumors prognosis. Methods Clinical data from 40 children with INI1-deficient tumors treated in Beijing Children’s Hospital from January 2012 to December 2022, along with the high-risk factors affecting prognosis, were retrospectively analyzed. Results Forty patients were diagnosed with INI1-deficient tumor at a median age of 32.5 months, including 31cases of malignant rhabdoid tumor, 4 cases of epithelioid sarcoma, 3 cases of malignant peripheral nerve sheath tumor, 1case of soft tissue myoepithelial carcinoma and 1 case of small cell carcinoma of the ovary with hypercalcemia. Thirteen patients(13/40, 32.5%) had metastases at diagnosis. Among the 40 patients, 21 patients died, including 6 patients with MRTK, 9 patients with EERT, 5 patients with AT/RT and 1 patients with SCCOHT. The overall survival rates of 1 years and 3 years for the entire cohort were 53.8%±8.0% and 43.6%±8.6% respectively. After survival analysis, it was clear that malignant rhabdoid tumor, lung metastasis and ki 67>60% had relatively poor outcomes. Lung metastasis was an independent risk factor for the prognosis of INI1-deficient tumor. Conclusion INI1-deficient tumor is a highly aggressive tumor in children especially with lung metastasis. Much work should do to improve the outcomes and survival for patients with aggressive INI1-deficient tumors.

BackgroundCommunicating bronchopulmonary foregut malformation is a rare anomaly characterized by a patent congenital communication between the esophagus or stomach and an isolated portion of the respiratory system. An esophagogram is taken as the gold standard for diagnosis. Compared with esophagography, computed tomography (CT) is more widely used and easily obtained, but CT findings have been described as nonspecific.PurposeTo describe CT findings in 18 patients with communicating bronchopulmonary foregut malformation to assist with early diagnosis.Material and methodsA retrospective review of 18 patients who had proven communicating bronchopulmonary foregut malformation between January 2006 and December 2021 was conducted. For each patient, the medical records, including demographics, clinical manifestations, upper gastrointestinal radiography, magnetic resonance imaging and CT findings, were reviewed.ResultsAmong the 18 patients, there were 8 males. The right to left ratio was 3.5:1. An entire lung was involved in 10 patients, a lobe or a segment was involved in 7 patients and an ectopic lesion was located in the right neck in 1 patient. The isolated lung may arise from the upper esophagus, mid-esophagus, lower esophagus or stomach, which were detected in 1, 3, 13, and 1 patient, respectively. On chest CT, an extra bronchus which did not arise from the trachea was detected in 14 patients. Contrast-enhanced chest CT was performed in 17 patients, the isolated lung receiving its blood supply from the pulmonary artery in 13 patients, the systemic artery in 11 patients and both pulmonary and systemic arteries in 7 patients.ConclusionsThe presence of an extra bronchus, which does not arise from the trachea, highly suggests the diagnosis of communicating bronchopulmonary foregut malformation. Contrast-enhanced chest CT can provide accurate information regarding the airways, lung parenchyma and vascular structures that is useful to plan surgery.

We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha-fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha-fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68 + macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient’s BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T + B low NK low immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient’s cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG -deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Background:Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, and its most common pathological types include embryonal RMS and alveolar RMS. In contrast, spindle cell RMS (SRMS) is a rare type. Moreover, the tongue is a rare primary site of RMS, and infancy is a rare age at onset. Case presentation:Two infants were diagnosed with lingual RMS at 3 and 5 months after birth, respectively, and were admitted to Beijing Children's Hospital. The pathological type in both cases was SRMS. Both were classified as low-risk and were treated with surgery and chemotherapy. Case 1 was in complete remission at the latest follow-up, and Case 2 had a relapse 10 months after stopping chemotherapy, achieving complete remission after the multimodal treatment of chemotherapy, surgery, and radiotherapy. The venous blood gene test of the two infants did not indicate a pathogenic mutation or a possible pathogenic mutation related to RMS. In Case 1, variants of the CDK4 and BRCA1 genes, both with unknown significance and a possible relation to RMS, were detected. In Case 2, three gene variants of unknown significance that were possibly associated with RMS-TRIP13, APC, and RAD54L-were identified. Conclusion:Lingual RMS in infants is rare. Its clinical manifestations lack specificity, and early recognition is complex. The success and timing of local treatment are important prognostic factors. Genetic testing may be helpful for the early detection of tumor susceptibility and the estimation of prognosis.

The study describes the clinical manifestations and variant screening of two Chinese siblings with primary ciliary dyskinesia (PCD). They carry the same DNAAF2 genotype, which is an extremely rare PCD genotype in the Chinese population. In addition, the study illustrated an overview of published variants on DNAAF2 to date. A two-child family was recruited for the study. Clinical manifestations, laboratory tests, bronchoscopic and otoscopic images, and radiographic data were collected. Whole blood was collected from siblings and their parents for whole-exome sequencing (WES) and Sanger sequencing to screen variants. The two siblings exhibited typical clinical manifestations of PCD. Two compound heterozygous variants in DNAAF2 were detected in both by WES. Nonsense variant c.156 C>A and frameshift variant c.177_178insA, which was a novel variant. The study identified a novel variant of DNAAF2 in Chinese children with a typical phenotype of PCD, which may enrich our knowledge of the clinical, diagnostic and genetic information of DNAAF2-induced PCD in children.