Clinical Manifestations In Children Research Articles

Impact of Interleukin-17 Receptor A Gene Variants on Asthma Susceptibility and Clinical Manifestations in Children and Adolescents

Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has been implicated in tissue inflammation and autoimmune diseases. As no previous studies have uncovered the potential role of IL17 receptor A (RA) gene variants in asthma risk, we aimed to explore the association of four IL17RA SNPs (i.e., rs4819554A/G, rs879577C/T, rs41323645G/A, and rs4819555C/T) with asthma susceptibility/phenotype in our region. TaqMan allelic discrimination analysis was used to genotype 192 individuals. We found that the rs4819554 G/G genotype significantly reduced disease risk in the codominant (OR = 0.15, 95%CI = 0.05–0.45, p < 0.001), dominant (OR = 0.49, 95%CI = 0.26–0.93, p = 0.028), and recessive (OR = 0.18, 95%CI = 0.07–0.52, p < 0.001) models. Similarly, rs879577 showed reduced disease risk associated with the T allele across all genetic models. However, the A allele of rs41323645 was associated with increased disease risk in all models. The G/A and A/A genotypes have higher ORs of 2.47 (95%CI = 1.19–5.14) and 3.86 (95%CI = 1.62–9.18), respectively. Similar trends are observed in the dominant 2.89 (95%CI = 1.47–5.68, p = 0.002) and recessive 2.34 (95%CI = 1.10–4.98, p = 0.025) models. For the rs4819555 variant, although there was no significant association identified under any models, carriers of the rs4819554*A demonstrated an association with a positive family history of asthma (71.4% in carriers vs. 27% in non-carriers; p = 0.025) and the use of relievers for >2 weeks (52.2% of carriers vs. 28.8% of non-carriers; p = 0.047). Meanwhile, the rs4819555*C carriers displayed a significant divergence in the asthma phenotype, specifically atopic asthma (83.3% vs. 61.1%; p = 0.007), showed a higher prevalence of chest tightness (88.9% vs. 61.5%; p = 0.029), and were more likely to report comorbidities (57.7% vs. 16.7%, p = 0.003). The most frequent haplotype in the asthma group was ACAC, with a frequency of 22.87% vs. 1.36% in the controls (p < 0.001). In conclusion, the studied IL17RA variants could be essential in asthma susceptibility and phenotype in children and adolescents.

Eating disorders in preschool and primary school children with autism spectrum disorder and its clinical significance

Autism spectrum disorder is the fastest growing form of nervous and mental development disorder in the world. In this regard, there is a special need to resolve issues of diagnosis and correction of not only the main symptoms of this disease, but also numerous associated somatic disorders. One of the common clinical manifestations in children with autism spectrum disorder is pathological eating behavior, which includes disturbances in eating habits and preferences, frequency of meals, etc. Despite the fact that eating disorders can also occur among normotypical coevals, in children with autism spectrum disorder, these manifestations are clinically more diverse, vary in severity and often appear earlier than the main symptoms of the disease. It must be emphasized that the correction of certain nutritional disorders in this group of children is often difficult due to the characteristics of the course of the underlying disease. This may be further exacerbated by increased parental anxiety. A timely solution to the problem of eating behavior in children with autistic disorder is of great importance for strengthening their health and reducing the severity of the underlying disease, since the connection between neuropsychic and somatic health is inseparable. In the review, we tried to identify the main factors involved in the formation of eating disorders in children with autism spectrum disorder, and presented existing practical tools for analyzing this medical problem and managing their nutrition for preventive and therapeutic purposes.

Characterization of otorhinolaryngologic manifestations in children with mucopolysaccharide storage disease typeⅠand type Ⅱ

Objective:To analyze the characteristics of otorhinolaryngological clinical manifestations in children with Mucopolysaccharide（MPS） type Ⅰ and type II in order to improve the knowledge of otorhinolaryngologists about this disease. Methods:Clinical data related to 55 children with MPS type Ⅰ and type II were retrospectively analyzed to investigate the clinical manifestations of MPS in ENT. Results:All 40 patients（72.72%） with MPS had at least one ENT symptom during the course of the disease, with 95% of them having an ENT symptom prior to the diagnosis of MPS; upper airway obstruction was the most common ENT symptom（34, 85.00%）, followed by recurrent upper respiratory tract infections（23, 57.50%）, and lastly, hearing loss（11, 27.50%）; all 26 patients had undergone at least one surgical procedure, of which 15（57.69%） had undergone ENT surgery, and all of these patients underwent ENT surgery before diagnosis. The most common ENT surgery was adenoidectomy. Conclusion:Early clinical manifestations of MPS patients are atypical, but the early and prevalent appearance of otolaryngologic symptoms and increased awareness of the disease among otolaryngologists has a positive impact on the prognosis of MPS.

Evaluating the relationship between the proportion of X-chromosome deletions and clinical manifestations in children with turner syndrome.

Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS). X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed. A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis (r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease (p = 0.26), central nervous system, thyroid, or liver disease. The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics.

Clinical profile during the first and second pandemic waves in children and adolescents with COVID-19 at pediatric public hospital, Rio de Janeiro, Brazil

Background: COVID-19 is usually milder in children and adolescents, leading to lower hospital admission rates than adults. This study evaluated clinical manifestations in children (< 10 years) and adolescents (10 to < 18 years) with COVID-19 admitted to a tertiary municipal hospital in Rio de Janeiro (Brazil) during the first (February to November 2020) and second pandemic waves (November 2020 to April 2021). Methods: this retrospective observational study considered patients in the pediatric age group (<18 years old) with confirmed diagnosis of COVID-19 using RT-PCR. Descriptive and bivariate analysis were performed assuming a p-value<0.05 level of significance for all analyses. Results: among the 34 included patients (50% boys; 73.5% children), the most prevalent symptom was fever (88.2%), followed by asthenia (85.3%), and cough associated with dyspnea (50%); 29.4% were admitted to the ICU, and 5.9% needed invasive mechanical ventilation. All patients were treated with antibiotics, 88.2% with antivirals, and 52.9% with corticosteroids. Asthenia was more frequent among children than adolescents (96.0% vs. 55.6%; p < 0.01). Tuberculosis was observed in none of the children, but 33.3% of the adolescents (p-value = 0.003). The percentage of hospitalized patients with family members infected with SARS-CoV-2 was smaller among children than adolescents (8.0% vs. 44.0%; p-value = 0.01). Other variables that differed between children and adolescents were C-reactive protein, creatinine, and need for non-invasive mechanical ventilation. There were no deaths among participants. Conclusion: in our hospital, COVID-19 was most often not severe in children and adolescents. Overall, children were hospitalized more frequently by COVID-19 than adolescents, with some differences for clinical characteristics.

Risk Factors for Severe and Critical Coronavirus Disease 2019 in Children.

Coronavirus disease 2019 (COVID-19) is generally mild in children; however, severe or critical cases may occur. In this nationwide study, we analyzed clinical manifestations in children diagnosed with severe acute respiratory syndrome coronavirus 2 to identify high-risk groups for severe or critical disease and compared the clinical features between the Delta- and Omicron-dominant periods. Data were retrieved from the National Health Insurance Service (NHIS) database and merged with the Korea Disease Control and Prevention Agency-COVID-19-NHIS cohort, which includes information on COVID-19 cases and vaccination records. We included individuals <20 years old diagnosed with COVID-19 during both periods (Delta: July 25, 2021-January 15, 2022; Omicron: January 16, 2022-March 31, 2022). Proportion of severe or critical cases was higher during the Delta period than during the Omicron period. The Omicron period saw increased hospitalization for pneumonia and croup and increased likelihood of hospitalization for neurological manifestations. The risk of severe COVID-19 depended on age group (Delta: highest for 12-19 years; Omicron: 0-4 years). This risk was high in children with multiple complex chronic conditions during both periods and with obesity or asthma during the Delta but not during the Omicron period. Two-dose COVID-19 vaccination provided strong protection against severe disease in the Delta period (adjusted odds ratio: 0.20), with reduced effectiveness in the Omicron period (adjusted odds ratio: 0.91). However, it significantly reduced the risk of critical illness (adjusted odds ratio: 0.14). These findings can facilitate identification of children at high risk of severe or critical COVID-19, who may require intensive medical support, and development of vaccination policies.

Correlation between immunoglobulin index level and disease severity and clinical manifestations in children with atopic dermatitis as a chronic inflammatory.

It was to analyze the clinical characteristics of atopic dermatitis (AD) in children and its relationship with immunoglobulin (IgG, IgA, IgM, IgE) levels. 400 children with AD in the dermatology clinic of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital(SCMC-FMU) were the study subjects, and 200 normal children were enrolled as the blank control. The clinical data of the included children were collected, and the serum immunoglobulin levels and other related indicators were measured. The results showed that the IgE level was higher observably in group A when we compared it with group A0, the IgE level was much higher in group B in comparison to group B0, group C showed higher IgE level C than in group C0, and it was the same case in groups D and D0(P < 0.05). The IgM level was decreased greatly in group C than that in normal children in group C0 (P < 0.05), but showed no visible difference among other groups (P > 0.05). The O-SCORAD scores of groups A, B, C, and D were significantly positively correlated with IgE level (P < 0.05). No great correlation was observed between skin dryness and IgE-specific allergen, IgG, IgA, IgM, and IgE levels in groups A - D (P > 0.05). Immunoglobulin deficiency was present in AD children compared with normal children, and IgE could be used as an efficient indicator to assess the severity of AD in children.

The Gut-Wrenching Effects of Cryptosporidiosis and Giardiasis in Children.

Cryptosporidium species and Giardia duodenalis are infectious intestinal protozoan pathogens that cause alarming rates of morbidity and mortality worldwide. Children are more likely to have clinical symptoms due to their less developed immune systems and factors such as undernutrition, especially in low- and middle-income countries. The severity of the symptoms and clinical manifestations in children may vary from asymptomatic to life-threatening depending on the Cryptosporidium species/G. duodenalis strains and the resulting complex stepwise interactions between the parasite, the host nutritional and immunologic status, and the gut microbiome profile. Structural damages inflicted by both parasites to epithelial cells in the large and small intestines could severely impair children's gut health, including the ability to absorb nutrients, resulting in stunted growth, diminished neurocognitive development, and other long-term effects. Clinically approved cryptosporidiosis and giardiasis drugs have broad antimicrobial effects that have incomprehensible impacts on growing children's gut health.

Selective IgM Deficiency: Evidence, Controversies, and Gaps.

Selective Immunoglobulin M deficiency (SIgMD) has been recently included in the inborn errors of immunity (IEI) classification by the International Union of Immunological Societies Expert Committee. The understanding of SIgMD is still extremely limited, especially so in cases of SIgMD in the pediatric population. The epidemiology of SIgMD in the pediatric population is still unknown. The pathogenesis of SIgMD remains elusive, and thus far no genetic nor molecular basis has been clearly established as a definitive cause of this primary immunodeficiency. Recurrent respiratory infections represent the main clinical manifestations in children, followed by allergic and autoimmune diseases. No conclusive data on the correct therapeutic management of SIgMD are available. Although, for most SIgMD patients, Ig replacement therapy is not required, it may be recommended for patients with significantly associated antibody deficiency and recurrent or severe infections. Prophylactic antibiotics and the prompt treatment of febrile illness are crucial. There is insufficient evidence on the prognosis of this condition. Therefore, further studies are required to define the disease trajectories and to increase our understanding of the molecular mechanisms underlying SIgMD in order to facilitate a better clinical, immunological, and prognostic characterization of the condition and develop tailored therapeutic management strategies.

Application of fluorescence in situ hybridization combined with chromosomal karyotyping analysis in children with disorders of sex development due to sex chromosome abnormalities

To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.

Surveillance and epidemiological characterization of human adenovirus infections among outpatient children with acute gastroenteritis during the COVID-19 epidemic in Shanghai, China

BackgroundHuman adenovirus (HAdV) has been recognized as one of the common enteric viruses associated with acute gastroenteritis (AGE) in children. The aim of this study was carried out to illustrate the epidemiological characterization of HAdV Infections among children younger than 15 years in Shanghai during COVID-19.MethodsDuring May 2020 and April 2022, 1048 fecal samples were collected from children ≤ 15 years diagnosed with AGE in the Children’s Hospital of Fudan University. HAdV was identified by PCR and sequenced with specific primers. All the obtained sequences were analyzed by MEGA (version 6.0). Demographic information and clinical features data were also collected and analyzed.ResultsIn total, 97 (9.3%, 97/1048) samples were detected to be HAdV during May 2020 and April 2022. We found an atypical upsurge in HAdV infection in the year 2021 after a major suppression in the year 2020. Approximately 84.5% (82/97) of HAdV-infected children were aged 0–60 months. Among the 97 HAdV-positive samples, only two species and five genotypes were detected. HAdV-F (88.7%, 86/97) was the most prevalent species and HAdV-F41 (87.6%, 85/97) was the most common genotype. Diarrhea, vomiting, and fever were the main clinical manifestations in children infected with HAdV. The children aged from 0 to 12 months showed simpler patterns of clinical presentation than those of children older than 13 months.ConclusionsOur findings described the epidemiological changes of HAdV infection in children with AGE during the COVID-19, which further underscored the importance of continuous surveillance of HAdV at both local and global scales.

Screening for Pompe Disease in High-Risk Pediatric Patients: Experience from a Tertiary Care Center in Rajasthan

AbstractA high index of suspicion is required to diagnose rare genetic disorders, such as Pompe disease, with common clinical manifestations in children. There is a need to sensitize physicians regarding cues to early screening and diagnosis of such patients. Minimal epidemiological data are available on Pompe disease in India. The aim of this study was to determine the prevalence of Pompe disease in high-risk pediatric populations and determine the appropriateness of screening dried blood spot (DBS) tests to facilitate the diagnosis of Pompe disease. We screened pediatric patients presented with (1) unexplained hypotonia, respiratory distress, cardiomyopathy, and elevated liver function tests; and (2) unexplained limb girdle muscle weakness through a DBS test for enzyme assay. Those patients found positive underwent acid alpha-glucosidase mutational analysis. This prospective cross-sectional study was conducted in 45 suspected patients after approval from the institutional ethical committee. Of the 45 suspected patients, 9 (20%) were found to be positive by DBS test. Out of these nine tested, four (44.4%) were positive, two (22.2%) were negative, and three (33.3%) could not be tested for mutation analysis. The prevalence of genetically confirmed Pompe disease in high-risk populations was 8.8%. The results of this study show that clinical suspicion and DBS filter paper test facilitate early diagnosis and management, thereby improving the quality of life in patients. DBS test acts as a robust, rapid first-tier screening test for Pompe disease.

Hypervirulent Strains of Neisseria meningitidis and Clinical Manifestations in Children With Invasive Meningococcal Disease.

Hypervirulent clonal complex (cc) have been associated with higher incidence and case fatality rate of invasive meningococcal disease (IMD). The aim of this study was to describe the clinical manifestations of the hypervirulent cc of meningococcus in children. Retrospective study in patients hospitalized by IMD microbiologically confirmed at three children's tertiary health care centers in Santiago, Chile, between 2010 and 2018. Demographic, clinical information and determination of the cc and factor H binding protein (fHbp) alleles were performed. In total 93 cases were evaluated, sequence typing was available for 91 cases, and 87 (95.6%) had a cc assigned; 63.7% were MenW and 31.8% MenB. The median age was 9 months, 67% were male and 18.7% had any comorbidity. A 26.4% presented neurological deficit, 25.3% petechiae and 20% diarrhea. Sixty-seven percent were admitted to the pediatric intensive care unit (PICU) and the case fatality rate was 9.9%. Regarding cc and fHbp alleles, ST11, ST41/44 and allele 22 were the most frequently identified, with 63.7%, 19.8% and 72.5%, respectively. We found statistically significant differences between the cc and presence of petechiae, diagnosis of meningococcemia plus meningitis, admission and days in PICU and advanced support. Allele 22 for fHbp was associated with the absence of petechiae, low suspicion of IMD, less diagnosis of meningitis+meningococcemia, PICU admission, advanced support and adrenal insufficiency. Epidemiological and microbiological surveillance of IMD should integrate clinical and laboratory components, including molecular and genetic characterization, to enrich the dynamic understanding of the clinical evolution of IMD.

Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.

Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review.

Sensitization to nsLTP: A Retrospective Study in An Italian Pediatric Population over the Last Decade.

Food allergy is common in the Mediterranean, especially concerning lipid transfer proteins (LTPs) allergy. LTPs are widespread plant food allergens in fruits, vegetables, nuts, pollen, and latex. Also, LTPs are prevalent food allergens in the Mediterranean area. They can sensitize via the gastrointestinal tract and cause a wide range of conditions: from mild reactions, such as oral allergy syndrome, to severe reactions, such as anaphylaxis. LTP allergy in the adult population is well described in the literature, concerning both the prevalence and clinical characteristics. However, there is poor knowledge about its prevalence and clinical manifestation in children living in the Mediterranean. This study, including 800 children aged from 1 to 18 years, investigated the prevalence of 8 different molecules of nonspecific LTP over time in an Italian pediatric population visited over the last 11 years. About 52% of the test population was sensitized to at least one LTP molecule. For all the LTPs analyzed, sensitization increased over time. In particular, using the years 2010 through 2020 as a comparison, the major increases were observed for the LTPs of the English walnut Jug r 3, the peanut Ara h 9, and the plane tree Pla a 3 (about 50%); the increase of the LTP of the Hazelnut Cor a 8 was about 36%, and that of the LTP of the artemisia Art v 3 was approximately 30%. The latest evidence in the literature indicates an increase in food allergy prevalence in the general population, including children. Therefore, the present survey represents an interesting perspective about the pediatric population of the Mediterranean area, exploring the trend of LTP allergy.

Pathomorphology of cutaneous mastocytosis

Introduction. Mastocytosis as a result of mast cell infiltration of the skin and other organs develops at any age. The relevance of this work is determined by the lack of systematic data on the pathomorphological features of the clinical forms and types of cutaneous mastocytosis, defined by the Consensus European-American Mastocytosis Group and the WHO classification in 2016. The variability of dermatological clinical manifestations in children and adults, the difficulties in interpreting laboratory tests create a problem for verifying the diagnosis and further treatment. The aim. To determine the main pathohistological features of clinical forms and types of cutaneous mastocytosis. Material and methods. The article includes data from patients who were treated and monitored at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology in 2019–2022. Results. The literature and own data on the characteristic pathomorphological patterns that are important for the diagnosis of mastocytosis with skin lesions in children and adults are systematized. The pathological substrate of lesions in diffuse cutaneous mastocytosis and mastocytoma was a massive infiltrate of mast cells in the papillary and reticular layers of the dermis. The histological picture in the monomorphic type of maculopapular cutaneous mastocytosis (MPCM) in children was characterized by a relatively lower density of mast cell infiltration of the papillary dermis compared to other clinical forms of mastocytosis. Also, in children, the density of mast cells in the affected skin was significantly higher compared to adults. In addition, in adults with PPCM, the papillary dermis was less infiltrated with mast cells. This confirms the opinion that the monomorphic type of MPCM in children is phenotypically similar to MPCM in adults. Conclusions. Further prospective follow-up of patients may allow conclusions to be drawn about the prognostic value of pathological examination in mastocytosis in adults and children.

Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients.

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.

Clinical and genetic characteristic in patients with disorders of sex development caused by Y chromosome copy number variant

Objective: To investigate the clinical phenotype and genetic characteristics of disorders of sex development (DSD) caused by Y chromosome copy number variant (CNV). Methods: A retrospective analysis was performed on 3 patients diagnosed with DSD caused by Y chromosome CNV admitted to the First Affiliated Hospital of Zhengzhou University from January, 2018 to September, 2022. Clinical data were collected. Clinical study and genetic test were performed by karyotyping, whole exome sequencing (WES), low coverage whole genome copy number variant sequencing (CNV-seq), fluorescence in situ hybridization (FISH) and gonadal biopsy. Results: The 3 children, aged 12, 9, 9 years, the social gender were all female, presented with short stature, gonadal dysplasia and normal female external genital. No other phenotypic abnormality was found except for case 1 with scoliosis. The karyotype of all cases were identified as 46, XY. No pathogenic vraiants were found by WES. CNV-seq determined that case 1 was 47, XYY,+Y(2.12) and case 2 was 46, XY,+Y(1.6). FISH concluded that the long arm of Y chromosome was broken and recombined near Yq11.2, and then produced a pseudodicentric chromosome idic(Y). The karyotype was reinterpreted as mos 47, X, idic(Y)(q11.23)×2(10)/46, X, idic(Y)(q11.23)(50) in case 1. The karyotype was redefined as 45, XO(6)/46, X, idic(Y)(q11.22)(23)/46, X, del(Y)(q11.22)(1) in case 2. 46, XY, -Y(mos) was found by CNV-seq in case 3, and the karyotype of 45, XO/46, XY was speculated. Conclusions: The clinical manifestations of children with DSD caused by Y chromosome CNV are short stature and gonadal dysgenesis. If there is an increase of Y chromosome CNV detected by CNV-seq, FISH is recommended to classify the structural variation of Y chromosome.

Neurological Complications in MIS-C: Case Report

COVID-19 has seriously affected children and the whole world. Pediatric multi-system inflammatory syndrome (MIS-C), a new syndrome that has not been known before, has been described. Although MIS-C may progress with different clinical manifestations in children, neurological involvement is reported relatively rarely. A 12-year-old girl with cerebral palsy and motor mental retardation was admitted to the emergency department with complaints of cough, fever, mouth sores and malnutrition. As a result of the evaluation, the patient was hospitalized to investigate the etiology of the fever and empirical antibiotic treatment was started, and she developed a rash on the 3rd day and tonic-clonic convulsions on the 5th day. The patient was hospitalized in the pediatric intensive care unit (PICU), and COVID-19 IgG and IgM were positive. Cerebral imaging of the patient was reported as normal. The patient with fever, rash, convulsions lasting longer than five days, and compatible laboratory results were diagnosed with MIS-C. Intravenous immunoglobulin (IVIG) and methylprednisolone treatments were started, and the patient was discharged on the 14th day of hospitalization, whose condition improved. This case is presented as an example of the rare neurological involvement of MIS-C. Detailed clinical investigation and neurological examination are required to exclude neurological sequelae of COVID-19 during the pandemic. The development of general guidelines that can combine them would be instructive.

Association of Antiphospholipid Antibodies with Clinical Manifestations in Children with Systemic Lupus Erythematosus.

The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE). We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group. Values of aPLA were defined in reference laboratories. The disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, whereas tissue damage degree was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR DI; SDI; DI). Research in our center showed that patients with cSLE often had hematological, cutaneous, and non-thrombotic neurological manifestations. Antiphospholipid antibodies may be present transiently or permanently. A significant change in the titer value was observed in the IgG isotype of aCLA. The presence of higher values of IgM β2GP1 at the beginning indicates that higher disease activity can be expected. Higher disease activity correlates with greater tissue damage. Additionally, it has been shown that aPLA positive patients have two and a half times higher risk of tissue damage than aPLA negative ones. Our study shows that the presence of antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus may indicate a higher risk of tissue damage, but since it is a rare disease in childhood, prospective and multicenter studies are necessary to assess the importance of the presence of these antibodies.