Congenital Research Articles

Homozygosity for a hypomorphic mutation in frizzled class receptor 5 causes syndromic ocular coloboma with microcornea in humans.

Ocular coloboma (OC) is a congenital disorder caused by the incomplete closure of the embryonic ocular fissure. OC can present as a simple anomaly or, in more complex forms, be associated with additional ocular abnormalities. It can occur in isolation or as part of a broader syndrome, exhibiting considerable genetic heterogeneity. Diagnostic yield for OC remains below 30%, indicating the need for further genetic exploration. Mutations in the Wnt receptor FZD5, which is expressed throughout eye development, have been linked to both isolated and complex forms of coloboma. These mutations often result in a dominant-negative effect, where the mutated FZD5 protein disrupts WNT signaling by sequestering WNT ligands. Here, we describe a case of syndromic bilateral OC with additional features such as microcornea, bone developmental anomalies, and mild intellectual disability. Whole exome sequencing revealed a homozygous rare missense variant in FZD5. Consistent with a loss-of-function effect, overexpressing of fzd5 mRNA harboring the missense variant in zebrafish embryos does not influence embryonic development, whereas overexpression of wild-type fzd5 mRNA results in body axis duplications. However, in vitro TOPFlash assays revealed that the missense variant only caused partial loss-of-function, behaving as a hypomorphic mutation. We further showed that the mutant protein still localized to the cell membrane and maintained proper conformation when modeled in silico, suggesting that the impairment lies in signal transduction. This hypothesis is further supported by the fact that the variant affects a highly conserved amino acid known to be crucial for protein-protein interactions.

Cardiac involvement in dermatological disorders: A narrative review

Recent studies have highlighted several pathogenic connections between skin disorders and cardiac manifestations. Dermatologists frequently encounter several genetic or inherited skin conditions that can have significant cardiac implications, including septal defects, cardiomyopathy, and valvular heart disease, which may sometimes be life-threatening. In this review, primary cutaneous disorders having cardiac manifestations are described. A comprehensive narrative review of the literature was conducted by searching articles published through November 2023 in the PubMed and Google Scholar databases. Original research articles, review articles, case reports, case series and other relevant English-language publications were included. The review identified several congenital diseases, inflammatory conditions, connective tissue disorders, and adverse drug reactions that have both skin and cardiac involvement. Diagnosing these cardiac manifestations in patients with skin conditions is crucial for appropriate management, timely intervention and effective patient counselling.

Musculoskeletal Sepsis in the Pediatric Intensive Care Unit

Background: Childhood bone and joint infection (BJI) ranges in severity, with the most unwell children requiring pediatric intensive care unit (PICU) support. We describe demographic and prehospital features of BJI cases associated with PICU admission and report treatment outcomes and costs for these cases. Methods: This study includes a retrospective cohort of children ≤15 years of age hospitalized with acute hematogenous osteomyelitis or septic arthritis in Auckland between 2018 and 2023. Cases admitted to PICU were compared to non-PICU hospitalized BJI cases. Direct medical hospitalization costs, treatment type and outcomes were described up to 1 year following discharge. Results: Of 563 BJI cases, 43 (8%) were admitted to PICU. PICU cases had shorter prehospital symptom duration (3.78 vs. 5.73 days, P = 0.0002). Sensitive Staphylococcus aureus was equally likely to cause disease in PICU and non-PICU cases (P = 0.86). Average hospitalization was longer (35.78 vs. 8.71 days, P ≤ 0.0001) for those admitted to PICU. Readmission and complication rates were both higher within the first year. Average cost per admission was $378,120 NZ dollars (±$796,891.64) for PICU cases versus $32,219 (±$201,797.33), P = 0.01 for cases not requiring PICU admission. In regression analysis, Māori ethnicity, previous history of infections and congenital conditions were statistically associated with PICU admission. Conclusion: In this study, children admitted to PICU with severe BJIs were more likely to have a history of congenital conditions or previous infections. Those of Māori ethnicity are overrepresented. Children treated in PICU have longer hospitalizations and experience more adverse outcomes at 1 year following discharge.

САМОДЕТЕРМИНАЦИЯ КАК ФАКТОР ПОЗИТИВНОЙ ТРАНСФОРМАЦИИ ПРОФЕССИОНАЛЬНО-ТРУДОВОЙ Я-КОНЦЕПЦИИ ЛИЦ С НАРУШЕНИЯМИ ОПОРНО-ДВИГАТЕЛЬНОГО АППАРАТА

The article is devoted to the problem of professional and personal development of persons with musculoskeletal disorders. The purpose of the study was to identify the characteristics of the development of the image of the professional “I” in this category of students and its transformation in the process of studying at the university. According to the developed system-dynamic theory of the professional-labor self-concept of persons with musculoskeletal disorders, the process of its transformation occurs during the period of professional training. The types of such transformation are identified: negative, neutral and positive. The study involved 106 students with musculoskeletal disorders studying in educational institutions of secondary vocational and higher education in various areas of training. It is hypothesized that the dominant factor in the positive transformation of the professional and labor self-concept of students with musculoskeletal disorders is self-determination as their ability to independently manage their professional and personal development, make informed choices, make meaningful decisions taking into account real opportunities and potential abilities. The hypothesis was verified using a self-determination scale and a methodology for identifying students’ self-esteem as subjects of future professional activity. It has been revealed that many students with congenital disorders of the musculoskeletal system are characterized by an orientation towards external reinforcement and a desire for super-achievement, which leads to the formation of maladaptive types of professional and labor self-concept, which impede their successful integration into society. It is concluded that students with musculoskeletal disorders require psychological support aimed at developing their subjective position, developing the need for autonomy and overcoming the syndrome of “learned helplessness” through correction of their motivational sphere and assistance in understanding the internal motives of their future professional career. activities.

Meta-analysis of Genetic Factors Responsible for Syndromic Anorectal Malformations in Children

Aim Anorectal malformation (ARM) is a congenital malformation that affects the anus or rectum area in children with an average age of 4 years. Different types of ARM are observed in males and females, each with distinct characteristics. The malformation is generally detected in the postnatal period, with a mortality rate between 3% and 16%. The study is conducted to understand the clinical significance of the mutation in the genes that are responsible for enhanced incidences of syndromes and their direct correlation with ARM. Methods Meta-analysis was performed using MedCalc statistical software, and we explored a strong association between ARM and syndromes using an odds ratio with a 95% confidence interval (CI). Results In total, 18 syndromes were found with the clinical characteristics of ARM. A maximum number of cases were reported about Currarino syndrome, with the minimum and maximum association of 30% and 100%, respectively. The results obtained for the pooled studies were I2 = 92.85%, P value ≤ .0001, and CI = 91.36-94.08. Conclusion A strong association has been identified between ARM and various congenital syndromes, highlighting the fact that genetic factors play a significant role in its occurrence. This association can help in the early diagnosis of the anomaly so that proper management can be presented at the earliest.

CLINICAL FEATURES OF COVID-19 INFECTION IN NEWBORNS: A RETROSPECTIVE ANALYSIS

Background. The COVID-19 pandemic has significantly impacted all age groups, including newborns. During the fifth surge, the prevalence of the Omicron variant among infants increased dramatically. While SARS-CoV-2 is generally milder in children than adults, newborns are vulnerable due to their immature immune systems. Clinical manifestations in newborns can range from asymptomatic to severe cases with respiratory distress or multi-organ dysfunction. Purpose of study. Description of clinical manifestations, course and outcomes of coronavirus infection in newborns. Materials and methods of study. A retrospective analysis was conducted on 110 newborns with COVID-19 admitted to the Children’s Clinical Infectious Diseases Hospital of Almaty between 2021 and early 2022. The study used electronic medical records as the source of research data. Demographic data such as age and sex were collected, along with epidemiological data including international or domestic travel within two weeks prior to the onset of the disease, known exposure to a person with positive SARS-CoV-2 infection, and a history of pregnancy. Results. The infants’ mean age was 17 days, with 44 boys (40%) and 66 girls (60%). Four newborns were admitted to the hospital at less than seven days of life. When analyzing the severity of the cases, the following proportions of newborns were observed: (3/110, 2.7%) were asymptomatic, (44/110, 40%) had mild symptoms, (57/110, 51.8%) were moderately severe, (4/110, 3.6%) severe, and (2/110, 1.8%) had very severe illness. The majority (68.4%) were hospitalized within three days of symptom onset. Fever was common, and all infants underwent chest CTs. Despite some severe cases, 99% had favorable outcomes, with only one fatality. Conclusion. This study indicates that most COVID-19 infections in newborns were contracted from household contacts. Clinical symptoms in infants included fever, catarrhal symptoms, and signs of intoxication, with some showing normal temperatures. Laboratory findings varied, with common changes including monocytosis and neutrophilia. Respiratory complications, such as bronchitis and pneumonia, were prevalent. Comorbidities, particularly congenital disorders, increased the risk of severe outcomes and mortality. Most newborns recovered within 1-2 weeks, though viral carriage persisted in many.

The molecular consequences of FOXF1 missense mutations associated with alveolar capillary dysplasia with misalignment of pulmonary veins

BackgroundAlveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a fatal congenital lung disorder strongly associated with genomic alterations in the Forkhead box F1 (FOXF1) gene and its regulatory region. However, little is known about how FOXF1 genomic alterations cause ACD/MPV and what molecular mechanisms are affected by these mutations. Therefore, the effect of ACD/MPV patient-specific mutations in the FOXF1 gene on the molecular function of FOXF1 was studied.MethodsEpitope-tagged FOXF1 constructs containing one of the ACD/MPV-associated mutations were expressed in mammalian cell lines to study the effect of FOXF1 mutations on protein function. EMSA binding assays and luciferase assays were performed to study the effect on target gene binding and activation. Immunoprecipitation followed by SDS‒PAGE and western blotting were used to study protein‒protein interactions. Protein phosphorylation was studied using phos-tag western blotting.ResultsAn overview of the localization of ACD/MPV-associated FOXF1 mutations revealed that the G91-S101 region was frequently mutated. A three-dimensional model of the forkhead DNA-binding domain of FOXF1 showed that the G91-S101 region consists of an α-helix and is predicted to be important for DNA binding. We showed that FOXF1 missense mutations in this region differentially affect the DNA binding of the FOXF1 protein and influence the transcriptional regulation of target genes depending on the location of the mutation. Furthermore, we showed that some of these mutations can affect the FOXF1 protein at the posttranscriptional level, as shown by altered phosphorylation by MST1 and MST2 kinases.ConclusionMissense mutations in the coding region of the FOXF1 gene alter the molecular function of the FOXF1 protein at multiple levels, such as phosphorylation, DNA binding and target gene activation. These results indicate that FOXF1 molecular pathways may be differentially affected in ACD/MPV patients carrying missense mutations in the DNA-binding domain and may explain the phenotypic heterogeneity of ACD/MPV.

Genomic complexity and clinical significance of the RCCX locus.

Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX-CAH due to CYP21A2 deficiency.

Genetic Association Between Blood Metabolites and Craniosynostosis: A Mendelian Randomization Study.

Craniosynostosis is a congenital disorder characterized by the premature fusion of cranial sutures, leading to abnormal skull development and potential neurodevelopmental complications. The role of metabolic influences in craniosynostosis remains underexplored. This study investigates the causal relationship between specific blood metabolites and the risk of craniosynostosis using a 2-sample Mendelian randomization (MR) approach. Genetic instruments were selected from a genome-wide association study on blood metabolites and craniosynostosis data from the FinnGen database. The MR analysis was conducted using inverse variance weighted regression as the primary method, with MR-Egger and weighted median methods as sensitivity analyses. Additional tests for pleiotropy and heterogeneity were performed to validate the robustness of the findings. The analysis identified significant associations between elevated levels of gamma-glutamylglycine [odds ratio (OR) = 2.379, 95% CI = 1.261-4.488, P = 0.007], N6-acetyllysine (OR = 2.731, 95% CI = 1.081-6.901, P = 0.034), phosphocholine (OR = 2.205, 95% CI = 1.226-3.658, P = 0.038) and glycine (OR = 2.118, 95% CI = 1.226-3.658, P = 0.007) with an increased risk of craniosynostosis. Conversely, higher levels of 3-hydroxy-2-methylpyridine sulfate (OR = 0.411, 95% CI = 0.1717-0.988, P = 0.047) and 5,6-dihydrothymine (OR = 0.293, 95% CI = 0.098-0.876, P = 0.028) were associated with reduced risk. Sensitivity analyses confirmed the robustness of these findings, with no significant evidence of pleiotropy or heterogeneity detected. This study provides evidence that specific blood metabolites may causally influence the risk of craniosynostosis, suggesting potential metabolic pathways that could be targeted for therapeutic intervention. These findings help to develop metabolite-based strategies for the prevention and treatment of craniosynostosis.

Most common congenital syndromes with facial asymmetry: A narrative review.

Symmetry is present in various aspects of everyday life. A symmetrical face is considered attractive, whereas a lack of facial symmetry is regarded as a source of functional and aesthetic problems. Most of the people exhibit slight asymmetries, but some of them reveal severe asymmetries. Among patients presenting with severe facial asymmetries, there may be those with congenital defects. Congenital defects may manifest at the time of birth or be a result of birth trauma.One of the most prevalent asymmetrical birth defects is cleft lip and/or cleft palate. Other congenital defects include craniofacial syndromes, such as Treacher Collins syndrome (TCS) and Goldenhar syndrome. Among the rare syndromes with facial asymmetries, Klippel-Feil syndrome (KFS), PHACE (posterior fossa brain malformation, hemangiomas, arterial anomalies, cardiac anomalies, and eye abnormalities) syndrome, plagiocephaly, and Parry-Romberg syndrome are worth noticing. The majority of craniofacial asymmetries require surgery to improve the patient's facial appearance. The treatment is multidisciplinary and long, and the most common procedures involve reparative and regenerative surgeries. The aim of this review was to present the most common congenital defects with facial asymmetry.

The Triple Procedure in Patients with Congenital Aniridia

Background: Aniridia is a rare panocular, bilateral, and congenital disease characterized by complete or partial iris hypoplasia and foveal hypoplasia, leading to decreased visual acuity and nystagmus. AAK, also referred to as aniridic keratopathy, manifests as corneal surface damage, epithelial thinning or loss, inflammation with immune cell infiltration, vascularization, and chronic progressive opacification. Methods: Twenty-one eyes in eighteen patients with aniridia underwent the triple procedure for visual rehabilitation. Subjects with stromal scarring with mild limbal deficiency were qualified for surgery. The majority of them developed stage II (15), and a few of them had third-degree (6) aniridic keratopathy. Results: The mean patient age was 38.4 ± 8.8. Visual acuity after one year of observation ranged from 0.4 in two eyes to 0.2 in nine eyes to below 0.1 in ten eyes. In the second year, VA remained at the same level in 13 patients (72.2%). In the third year, four patients (22.2%) experienced recurrence of AAK. Conclusions: A majority of the ARK cases (72.2%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes.

Concurrent diagnosis of severe haemophilia A and acute lymphoblastic leukemia in a child: First report in Greece

Haemophilia A is a congenital bleeding disorder resulting by deficiency of coagulation factor VIII and Acute Lymphoblastic Leukemia (ALL) Is the most common cancer type in children. The concurrence of hemophilia and ALL in pediatric patients is quite rare. We report a case of a 2.5 year old boy, with an uneventful past history, which presented with pallor, petechiae, ecchymoses and lethargy to the emergency department. A full blood count on admission revealed severe leukocytosis, anemia and thrombocytopenia. Diagnosis of ALL was confirmed and the patient was put on chemotherapy. Excessive bleeding from the site of entry of the central venous catheter led to complementary testing, which revealed very low levels of Factor VIII and severe Haemophilia A was also diagnosed. The patient suffered from minor gastrointestinal bleeds and a severe intrabdominal hemorrhage due to an abcess eruption during his treatment for ALL. To date, very few cases of ALL and Haemophilia have been reported in children, and due to this rarity there are no guidelines concerning the adjustments in treatment in this small population of patients.

Risk factors for abusive head trauma in the pediatric population.

Abusive head trauma (AHT) is the leading cause of death from physical child abuse in children younger than 5 years of age in the United States. The mortality rate among patients with AHT is 25%, and the recurrence rate of child abuse rises to 35% when there is a lack of intervention. Thus, identifying child abuse is crucial yet especially challenging for infants and toddlers as they are preverbal. Current guidelines for child abuse do not sufficiently address the specific needs of a younger population. This study aimed to evaluate clinical factors associated with abuse among such populations. The National Trauma Data Bank was queried from 2017 to 2019 for patients younger than 3 years with acute head trauma. Patients who were suspected of having experienced child abuse (suspected child abuse [SCA] group) were propensity score matched with patients who were not suspected of having experienced child abuse (non-SCA group) based on demographics, comorbidities, and Glasgow Coma Scale (GCS) scores. Paired Student t-test and chi-square tests were used to compare differences in hospital outcomes between the two groups. Multivariable regression analysis was used to determine factors associated with SCA (p < 0.05). The authors identified 10,844 patients in the SCA group and 27,912 in the non-SCA group. Regression analysis results showed that patients in the SCA group had higher rates of prematurity (OR 2.30, p < 0.001), GCS scores < 13 (OR 1.79, p < 0.001), congenital disorders (OR 1.56, p < 0.001), and public insurance use (68.38% vs 52.88% p < 0.001). Black and Hispanic patients were more likely to be in the SCA group (OR 1.56, p < 0.001 and OR 1.35, p < 0.001, respectively). Following propensity score matching, SCA patients had a longer length of hospital stay (3.17 vs 1.34 days, p < 0.001) and higher mortality rate (4.89% vs 3.58%, p < 0.001). Acute head injuries in the SCA group were associated with prematurity, congenital disorder, low GCS score, and public insurance use. As such, the current guidelines should implement clinical history and insurance type to better reflect the at-risk patient population when evaluating infants and toddlers for potential abuse. There could be overidentification of child abuse among Black and Hispanic patients, and further research is warranted.

Characteristics of Children Ages 1-17 Who Died of COVID-19 in 2020-2022 in the United States.

This study describes characteristics of children ages 1 to 17 years who died of coronavirus disease 2019 (COVID-19) in 2020 to 2022 and whose deaths were reviewed by child death review (CDR) teams across the United States. We used data in the National Fatality Review-Case Reporting System to examine children who died of COVID-19. Deaths were determined because of COVID-19 from death certificates or CDR determinations. A total of 183 children 1 to 17 years old who died of COVID-19 were reported in the National Fatality Review-Case Reporting System. One-third (33%) were 15- to 17-year-olds, and 26% were 1- to 4-year-olds. Fifty-six percent were reported as male, 54% white, 24% Black, and 18% Hispanic ethnicity. Physicians declared cause of death in at least 82% of deaths. More than two-thirds (68%) had a medical condition (excluding COVID-19) at time of death. The most common conditions were nervous system disorders (19%), congenital disorders (14%), obesity (12%), respiratory disorders (12%), and neurodevelopmental disorders (10%). Of children with an underlying condition, 35% had 3 or more conditions. Less than half (42%) had contact with a health care provider within a month of their death; and three-fourths died within 14 days of exposure. This study describes the demographics, death investigation findings, and medical conditions of children who died of COVID-19. The results highlight the short timeline between COVID-19 exposure and death. Pandemic planning that prioritizes prevention efforts and timely access to effective medical care may result in saving children's lives.

Current Practice and Perspectives on Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Antibody Deficiency Among Specialized Nurses in Poland

Background/Objectives: Inborn errors of immunity (IEI) encompass various congenital disorders, resulting in immunity defects and recurrent infections. Home-based subcutaneous immunoglobulin replacement therapy (scIgRT) is the best treatment option for those with primary antibody deficiency (PAD). However, the lack of standardized procedures in patient training remains a challenge. Our study investigates nurses’ practice and perspectives, aiming to identify areas for improvement in at-home scIgRT practice. Methods: We prepared a structured survey regarding scIgRT, including needle choice experience and perception of adverse events, and distributed it among qualified nurses involved in patient training and scIgRT supervising. Results: We included 56 nurses with a median age of 50 years. Among them, 67.9% represented adult care providers, while 32.1% supervised IgRT in children. Most respondents (83.9%) used the classic or assisted with hyaluronidase scIgRT preparations. Single-channel needles were administered most commonly (85.7%). The needle length was mostly chosen solely by a nurse (57.1%) or in cooperation with the patient (23.2%). Next, 9 mm and 12 mm needles were used most often (92.9% and 78.6%, respectively). As expected, the 6 mm needle was more frequently applied for children compared to adults (n = 16, 88.9% vs. n = 11, 28.9%, p &lt; 0.001), while 12 mm was primarily used in adults (n = 35, 92.1% vs. n = 9, 50.0%, p &lt; 0.001). Visual skin fold assessment was the basis for the needle selection (58.9%), followed by the injection site rule (26.8%) or a choice between two available needle types for thinner or thicker patients (25.0%). Results of this survey indicate that, according to nurses’ opinions presented in this survey, the needle length could be associated with local scIgRT adverse events, such as side needle leakage or local burning. Yet, it was likely unrelated to general adverse signs, such as headaches or dizziness. Most respondents (66.1%) indicated that, even if local adverse events occur, patients are reluctant to change scIgRT preparation or needle length. Most participants (69.6%) reported that the optimal administration technique needs to be discussed with the patient before and during scIgRT. Conclusions: This study sheds light on scIgRT practice in Poland, emphasizing deficiency in needle selection technique. Future research should focus on standardized training and advanced needle selection procedures on patient outcomes, investigating the correlation between needle strategies and adverse events, as well as the effectiveness of scIgRT.

Catheter ablation in a monochorionic diamniotic twin pregnancy: A case report and literature review.

Preexcitation syndrome is an uncommon congenital cardiac disorder that impairs the normal cardiac conduction system. Radiofrequency ablation is one of the most effective treatments for this condition. Nevertheless, radiofrequency ablation is rare in women with preexcitation syndrome during pregnancy. A 33-year-old woman with monochorionic diamniotic twin pregnancy complicated by sinus arrhythmia with ventricular preexcitation at 14 weeks and 5 days of gestation, with paroxysmal palpitations and shortness of breath at 16 weeks with paroxysmal supraventricular tachycardia with preexcitation syndrome and a heart rate ranging from 180 to 225 beats per minute. The pregnant occurred sudden palpitations and shortness of breath in the shower. Electrocardiography revealed paroxysmal supraventricular tachycardia, and electrophysiological study revealed preexcitation syndrome (dominant accessory route of the left free wall) with atrioventricular reentrant tachycardia. Radiofrequency catheter ablation was performed at 20 weeks. Symptoms of preexcitation syndrome resolved after the radiofrequency catheter ablation, and 2 healthy infants were delivered at 36 weeks and 2 days of gestation by cesarean section. Preexcitation syndrome may result in life-threatening arrhythmias such as supraventricular tachycardia during pregnancy and delivery. It might be efficiently controlled through optimal treatment by a multidisciplinary team, which would effectively minimize arrhythmia risk events during pregnancy and improve maternal-fetal outcomes. Based on the patient's individual situation, radiofrequency ablation may be a procedure in pregnant women with preexcitation syndrome.

The Impact of Maternal Passive Tobacco Smoke on Neonatal Myocardiopathy in Mice.

Tobacco smoke has a global impact, particularly on pregnant women and their newborns. An emerging body of research suggests that passive tobacco smoking is a significant contributor to congenital cardiovascular disorders (CVDs). This study aimed to mimic the effects of passive tobacco smoke (PTS) on neonates exposed throughout the gestational period. Female mice (DPC = 0) were exposed to PTS; 24 cigarettes/day with an interval of 10 min between each cigarette in a specialized smoke chamber from conception to birth. Histopathological analysis was employed to evaluate PTS-induced cardiac damage in neonates. The results revealed significant alterations in cell structure, namely, widened interstitial spaces, hemorrhage, pyknotic nuclei, inflammatory cell infiltration, collagen deposition, and fibrosis. Maternal exposure to PTS during pregnancy may lead to neonatal myocardiopathy.

Spinal Neurocutaneous Melanosis

Neurocutaneous melanosis is characterized by melanin-producing cells within the skin, leptomeninges, or brain parenchyma. It is a severe manifestation of congenital melanocytic nevus syndrome and can develop malignant melanomas. The disorder is commonly present in pediatric patients within the first two years of life and has a poor prognosis. We report a case of an 8-year-old male with epilepsy and cognitive deficit presenting spinal neurocutaneous melanosis.

Echocardiographic Screening Model for Improved Assessment of Atrial Septal Defect Closure: A Multicenter Retrospective Study.

Atrial septal defect (ASD) is a prevalent congenital heart condition in adults, which finally leads to pulmonary hypertension and right heart failure if left untreated. Right heart catheterization (RHC), the current gold standard for determining ASD closure feasibility, is invasive. Thus, a noninvasive prescreening tool is urgently needed. In a multicenter, retrospective study, we assessed 924 ASD patients (2012-2022) to determine their suitability for ASD closure. Using LASSO regression, we identified predictors for a correctable shunt, enabling us to create the ASD model. The ASD model, comprising of estimated pulmonary artery systolic pressure (ePASP), peak velocity through the pulmonary valve (PV), peak E-wave velocity through the tricuspid valve (TVE), and right atrial longitudinal dimension (RA) by echocardiography, was constructed and exhibited favorable discriminative capability with an area under the curve (AUC) of 0.941 (95% CI: 0.920-0.961) in the derivation group. The model also demonstrated good calibration and discriminative abilities in the validation cohort. When juxtaposed with the earlier congenital heart disease (CHD) model, the newly developed ASD model demonstrated superior predictive capabilities for correctable shunt, supported by the net reclassification index (NRI) [0.063 (95% CI: 0.001-0.127, p = 0.047)] and integrated discrimination improvement (IDI) [0.023 (95% CI: 0.011-0.036, p <0.001)]. In summary, our research advocates the ASD model as a superior tool for screening suitable ASD defect closure candidates.

Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community

BackgroundCongenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences.Results and discussionA questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks.ConclusionThis study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.