Birth Defects Research最新文献

{"title":"Assessing Environmental Risks Factors in Anorectal Malformations: Case Report and Literature Review","authors":"Claudia Ortiz-Fernandez,&nbsp;Ferran Campillo i López,&nbsp;Stephan Otto Schneider,&nbsp;Bernardo Núñez,&nbsp;Anton Foguet i Vidal","doi":"10.1002/bdr2.2445","DOIUrl":"https://doi.org/10.1002/bdr2.2445","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Anorectal malformations are birth defects that affect 1 in 5000 live births. Despite the research, the cause is still unknown, but genetic and environmental factors have been described to contribute to its pathogenesis. We report the case of a child with an anterior ectopic anus in which prenatal environmental factors were systematically assessed using a screening evaluation interview, the Green Page, and a complete Pediatric Environmental History.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A first born of a 29 year old woman with a history of epilepsy treated with high doses of lamotrigine, levetiracetam, and clobazam, and a subclinical hypothyroidism treated with levothyroxine. Periconceptional supplementation with 400mcg of folic acid, maternal and paternal smoking habit, and some occupational exposures to chemical hazards. No personal or family history of congenital malformations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Some previously related environmental factors were found, such as mother's epilepsy, high lamotrigine dose, tobacco exposure, air pollution, and in a lesser risk the use of levothyroxine. The Green Page and the Pediatric Environmental History could contribute to identifying and reducing environmental risks related to birth defects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intake of Trans-Fat Diet With Prenatal Bisphenol A Exposure Induce Global DNA Methylation in Rats Offspring","authors":"Hala Abulehia,&nbsp;Noor Shafina Mohd Nor,&nbsp;Siti Hamimah Sheikh Abdul Kadir","doi":"10.1002/bdr2.2450","DOIUrl":"https://doi.org/10.1002/bdr2.2450","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bisphenol A (BPA) is a ubiquitous industrial compound found in an enormous variety of consumer goods such as plastics, epoxy resins, and thermal paper. Despite its widespread usage, the effects of BPA on the risk and development of metabolic syndrome are not fully understood. Prenatal exposure to BPA has been shown to disrupt the development of offspring's metabolically active tissues and increase their susceptibility to the adverse consequences of a trans-fat diet (TFD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this experiment, pregnant rats (<i>n</i> = 18) were randomly separated into three groups. These groups were treated from pregnancy day (PD) 2 to PD 21. Subsequently, the male offspring of these rats were provided either a normal-diet (ND) or a TFD from 3rd postnatal week (PNW) to 14th PNW. Then, protein expression of PPAR-γ and global DNA methylation were assessed in the adult rat offspring that were exposed to in utero BPA and subjected to postnatal TFD intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study findings have shown that there was no association between prenatal exposure to BPA and/or TFD consumption and PPAR-γ protein expression within all the study groups in the liver tissue. On the other hand, changes at the molecular level, as reflected by the global DNA hypermethylation induced by prenatal BPA and postnatal TFD intake in adult male SD rat offspring (PNW 14).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study underscores the potential impact of prenatal BPA exposure and postnatal TFD intake on epigenetic regulation, as evidenced by global DNA hypermethylation, despite no observable changes in PPAR-γ protein expression. These findings suggest that early-life environmental exposures may predispose individuals to metabolic disruptions, including diabetes and obesity, in adulthood or future generations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equity in Early Life: Advancing Environmental Justice for Maternal and Child Health","authors":"Ayhan Ceri,&nbsp;Dogukan Keskin","doi":"10.1002/bdr2.2448","DOIUrl":"https://doi.org/10.1002/bdr2.2448","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Environmental justice (EJ) is essential for addressing the disproportionate burden of environmental hazards on vulnerable populations, particularly pregnant individuals and young children. Developmental sensitivity to toxic exposures, such as air pollution, lead, and endocrine-disrupting chemicals, is compounded by systemic inequities like food insecurity and housing instability. Structural racism and socioeconomic disadvantage further exacerbate these risks, leading to higher rates of preterm birth, low birth weight, and maternal morbidity in marginalized communities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study explores the intersection of environmental and social determinants of health, emphasizing EJ’s role in reducing disparities through community engagement, research, and policy reforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative review of policies, interventions, and case studies was conducted to assess effective EJ strategies in mitigating maternal and child health disparities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Successful community-driven initiatives, such as lead abatement programs and air quality improvements, demonstrate that aligning policies with community-identified priorities leads to measurable health benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>EJ-based interventions reduce environmental risks and health inequities through participatory research and systemic policy changes. However, challenges such as limited funding and data gaps require coordinated action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To promote maternal and child health equity, we recommend expanding funding, institutionalizing community engagement, and leveraging innovative data collection. By prioritizing community-led solutions, EJ can drive systemic transformation, ensuring better health outcomes for future generations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why Has Gastroschisis Increased Over Time and Why Is It More Common in Infants of Young Mothers?","authors":"Rashida S. Smith-Webb,&nbsp;Peter H. Langlois,&nbsp;Gary M. Shaw,&nbsp;Cynthia A. Moore,&nbsp;Mark A. Canfield,&nbsp;Julie M. Petersen,&nbsp;Martha M. Werler,&nbsp;the National Birth Defects Prevention Study","doi":"10.1002/bdr2.2436","DOIUrl":"https://doi.org/10.1002/bdr2.2436","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although many factors are associated with gastroschisis risk, studies have not systematically explored whether they account for its increasing frequency over the past decades or its inverse association with maternal age. We examined whether previously reported risk factors for gastroschisis from the National Birth Defects Prevention Study (NBDPS) explain the association with increasing temporal prevalence or young maternal age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the NBDPS (1997–2011), crude odds ratios (ORs) were calculated for birth years 2005–2011 versus 1997–2004 and maternal age &lt; 25 versus 25+ years. We then adjusted for 16 factors separately with logistic regression (paternal age, interpregnancy interval, parity, alcohol, cigarettes, illicit drugs, oral contraceptives, cold/flu with fever, genitourinary infection, polycyclic aromatic hydrocarbons, diet quality, prepregnancy body mass index, parental race and ethnicity, language spoken at home, years lived in the United States, and household income).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The birth year OR (1.28; 95% CI: 1.14, 1.44) was attenuated by 16% after adjustment for polycyclic aromatic hydrocarbon exposure (OR 1.08; 95 CI: 0.92, 1.26). The young maternal age OR (7.76; 95% CI: 6.71, 8.97) was attenuated by 30% after adjustment for paternal age (OR 5.43; 95% CI: 4.55, 6.48) and separately for interpregnancy interval (OR 5.45; 95% CI: 4.43, 6.69).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Some evidence suggests that risk factors for gastroschisis account for small amounts of the time trend and maternal age associations. However, it remains unclear what factors underlie the complete calendar time or maternal age associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Evaluation of Neural Tube Defect-Related Missense Mutations Using In Silico Methods","authors":"Burcu Biterge Sut","doi":"10.1002/bdr2.2453","DOIUrl":"https://doi.org/10.1002/bdr2.2453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube formation is one of the most important developmental events as it gives rise to the key organs comprising the central nervous system. Failure in the proper closure of the neural tube results in congenital abnormalities, namely neural tube defects (NTDs). Previous studies have identified several single nucleotide variations that are considered risk factors and established a genetic background for the increased incidence of NTDs and factors. This study aims to provide a comprehensive functional analysis of NTD-related missense mutations in terms of their potential effects on pathogenicity, protein stability, and structure using predictive in silico analysis tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single nucleotide variations associated with NTD risk were identified by a systematic review of previous studies on Pubmed and ClinVar. Protein stability and pathogenicity scores were predicted using MUpro and PloyPhen2, respectively. Structural alterations were determined via the HOPE server. Predicted expression profiles in the brain were retrieved from the Human Protein Atlas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis identified 43 NTD-related missense mutations in MTHFR, MTRR, PARD3, PACS1, MED12, VANGL1, VANGL2, FZD6, CELSR1, FUZ, DVL2, and LRP6 genes. We found that all of these genes are predicted to be expressed in different regions of the brain. We showed that single nucleotide variations resulted in decreased protein stability, and the majority of them were found to be damaging. We also report that the amino acid changes introduced by these mutations caused differences in size, charge, and hydrophobicity, which potentially resulted in structural alterations within the protein and affected their contacts with other proteins and ligands.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, this study provides a comprehensive analysis of NTD-related missense mutations regarding their potential damaging effects, which might contribute to the pathogenesis of NTDs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choosing Words to Limit Stigma: The Use of Person-First Language in Birth Defects Research","authors":"Jacqueline T. Bascom,&nbsp;A. J. Agopian","doi":"10.1002/bdr2.2449","DOIUrl":"https://doi.org/10.1002/bdr2.2449","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Birth defects are associated with psychosocial stress and stigma, in addition to increased mortality and lifelong disabilities. The language and phrasing used to describe individuals with birth defects in scientific writing can affect attitudes that contribute to stigma. Using a “person-first” writing structure (e.g., “infants with Down syndrome”) instead of “identity-first” language (e.g., “Down syndrome infants”) is intended to promote respect and inclusivity. Our work aims to enhance awareness and advocacy of person-first language among researchers and professionals in birth defects research, with the goal of reducing stigma and adopting language that prioritizes dignity for individuals and their families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 52 population-based birth defects articles published by the National Birth Defects Prevention Network (NBDPN) between 2002 and 2024, which we expect to exemplify writing practices among U.S. birth defects epidemiologists. We evaluated the use of person-first and identity-first language in population-based birth defects research and advocated for increased consideration of person-first language in the field.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 52 NBDPN articles reviewed, seven (13%) articles used person-first language only, <i>N</i> = 6 (12%) used identity-first language only, 38 (73%) used both, and one (2%) used neither.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We encourage researchers to consider using person-first language when describing individuals with birth defects in epidemiologic studies and in training birth defects epidemiologists, while acknowledging that some communities may also prefer an identity-first framework (e.g., the “Deaf community”).</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Separation Exhibits a Sex Dimorphism in Memory Impairments in Adolescent Rats: Acute Methylphenidate Administration as a Treatment","authors":"Fatemeh Mohtashami Borzadaran,&nbsp;Soheila Rezakhani,&nbsp;Reyhaneh Kamali,&nbsp;Khadijeh Esmaeilpour","doi":"10.1002/bdr2.2441","DOIUrl":"https://doi.org/10.1002/bdr2.2441","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Rodents are highly dependent on maternal care after birth. Disturbing mother and pup interactions leads to detrimental alternations for the rat and the mother. Maternal separation (MS) is an accepted model for investigating disruption of mother and pup relationship. In addition to other detrimental effects, MS is a model known to induce permanent changes in learning and memory. Methylphenidate has been effective in memory enhancement in individuals suffering from memory deficits, attention-deficit hyperactive disorder (ADHD), as well as healthy subjects for better performance in exams.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>In this research, a 21-day separation for 3 h was implemented, and the effects of MS on spatial and passive avoidance learning, and memory were evaluated in the mid-adolescence period of rats, in both males and females. Also, a drug intervention of a high therapeutic dose of 5 mg per kg was used in a five-day period in different control and MS groups. Morris water maze was utilized for spatial learning and memory analysis, and a shuttle box paradigm was used for passive avoidance learning and memory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through our behavioral tests, we have shown that MS can alter spatial learning and memory in males. On the other hand, females are protected from the detrimental effects of MS on spatial learning and memory. Furthermore, passive avoidance learning was not different among groups, be it male or female. However, in the case of memory evaluation in the passive avoidance test, the male did not exhibit a significant difference in step-through latency. However, maternally separated females had poor performance in the memory phase with shorter step-through latencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Methylphenidate compensated for the deleterious effects of MS on learning and spatial memory for the male group and passive avoidance memory in the female group at the behavioral level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Ensemble Learning Techniques for Infant Mortality Prediction: A Technical Analysis of XGBoost Stacking AdaBoost and Bagging Models","authors":"Indu Verma,&nbsp;Sanjeev Kumar Prasad","doi":"10.1002/bdr2.2443","DOIUrl":"https://doi.org/10.1002/bdr2.2443","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Infant mortality remains a critical public health issue, reflecting the overall health and well-being of a population. Accurate prediction of infant mortality is crucial, as it enables healthcare providers to identify at-risk populations and implement targeted interventions. By analyzing factors such as maternal education, prenatal care access, nutrition, and environmental influences, predictions help in designing effective programs aimed at reducing infant deaths.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This research paper aims to predict infant mortality in India by employing ensemble learning techniques, specifically eXtreme gradient boosting (XGBoost), stacking, adaptive boosting, and bagging. The data for the analysis are sourced from national surveys and demographic studies focusing on infant mortality in India. The collected data underwent rigorous preprocessing steps to prepare it for predictive modeling. Each ensemble learning model is applied to predict infant mortality rates based on the preprocessed data. The XGBoost handles complex and non-linear relationships within the data, and the stacking model is used for the accurate and robust predictions. The adaptive boosting model iteratively trains multiple weak learners, which makes the predictive model as stronger. The adaptive boosting technique enhances the performance of weak classifiers while effectively addressing class imbalance issues. Further, the bagging approach is implemented to derive the linear and non-linear relationships of infant mortality. Models were optimized using k-fold cross-validation to fine-tune their hyper parameters. The predictive ability of the ensemble techniques is analyzed by deploying using different performance parameters.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;XGBoost attained superior performance results, with a 98.75% accuracy, 98.56% precision, and 98.24% recall. The adaptive boosting model strengthened weak learners and addressed class imbalance issues, while the bagging method captures linear and non-linear relationships. Ensemble learning models demonstrated effectiveness in predicting infant mortality, with XGBoost excelling in handling complex and non-linear relationships.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The simulation results revealed that ensemble learning models are highly effective in predicting infant mortality rates in India, with significant regional disparities observed. For example, the Northeast region exhibited the highest predicted infant mortality rates, while the South region recorded the lowest. These findings underscore the need for targeted i","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variants in Chromatin Remodeling Genes Are Involved in Patients With Chiari Malformation Type 1","authors":"Ferruccio Romano,&nbsp;Maria Cerminara,&nbsp;Patrizia De Marco,&nbsp;Michele Iacomino,&nbsp;Marco Di Duca,&nbsp;Domenico Tortora,&nbsp;Marco Pavanello,&nbsp;Gianluca Piatelli,&nbsp;Marcello Scala,&nbsp;Federico Zara,&nbsp;Aldamaria Puliti,&nbsp;Valeria Capra","doi":"10.1002/bdr2.2446","DOIUrl":"10.1002/bdr2.2446","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Chiari malformation type 1 (CMI) is defined by the herniation of cerebellar tonsils of 5 mm or more, with possible neurological consequences, including compression of the neural tissue and/or anomalies in cerebral spinal fluid circulation. The etiology of CMI is not fully elucidated, with both genetic and environmental factors being involved. Several genes and pathways involved in bone development are pointed out like genes of the WNT, FGF, and BMP signaling pathways. More recently, the crucial role played by chromatin remodeling genes in the pathogenesis of CMI has increasingly emerged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this paper, we discuss a familial case of CMI and a single patient, harboring variants in chromatin remodeling genes, identified by whole exome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The first is a family with three affected members and one sibling with a cerebellar tonsil herniation of &lt; 5 mm. The three CMI patients harbor a heterozygous missense variant in the <i>SETD2</i> gene, whose truncating variants are responsible for Luscan–Lumish syndrome. A second variant in <i>HP1BP3</i>, a gene not previously associated with human pathology, with evidence of skeletal anomalies in mice models, was found in the three patients and also in the girl with a herniation of &lt; 5 mm. The second case is a proband with a de novo variant in <i>KMT2A</i>, associated with Wiedemann–Steiner syndrome, in which anomalies of the craniocervical junction are described.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We highlight the importance of chromatin remodeling genes in both isolated and syndromic CMI and suggest the potential role of <i>HP1BP3</i> as a possible modifier gene in CMI pathogenesis, even if this association needs to be further clarified.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Supra-Numerary Limb Grafted Onto a Sacrococcygeal Mass in a Child With Spinal Dysraphism: Case Report, Dysmorphogenesis, and Management Review","authors":"Kaylene Freitas,&nbsp;Leonor Castro,&nbsp;Carla Pilar,&nbsp;Catarina Barreira,&nbsp;Rosete Nogueira,&nbsp;Jenny Gonçalves","doi":"10.1002/bdr2.2447","DOIUrl":"https://doi.org/10.1002/bdr2.2447","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Externally attached supra-numerary body structures are a rare congenital malformation. Dysmorphogenesis remains controversial, hence many different classifications have been proposed over the years. We report a case of a supra-numerary lower limb grafted onto a sacrococcygeal mass in a child with a myelomeningocele. Prevailing theories for its origin are revised as well as prenatal and postnatal management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>The case relates to a female neonate with a third lower limb grafted to a lumbosacral mass found upon birth. Postnatal imaging revealed a lipomyelomeningocele and a supra-numerary limb. Surgical intervention was performed on day seven of life with removal of the supra-numerary limb and correction of the dural defect. Anatomopathologic study revealed mature and dysplastic tissues of the three germlines. The infant was discharged after 16 days to follow-up by a multidisciplinary team. In early follow-up, minor asymmetry in lower limb mobility, peri-anal anesthesia, and bladder incontinence was present. Currently 8 years old, the patient has no motor or sensory dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This case challenges the existing theories for conjoined twinning, as they do not fully explain the co-occurrence of neural tube defects in sacrally fused supra-numerary structures. Whether these malformations are entities of a single disease spectrum or the result of independent dysmorphogenesis is debated. Prenatal diagnosis with sequential investigation of morphogenesis as well as postnatal anatomopathological examination are crucial for a better understanding of complex biologic processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 2","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}