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Annual Review of Neuroscience 2014Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development... (Review)
Review
Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies.
Topics: Animals; Folic Acid; Genetic Predisposition to Disease; Humans; Neural Tube Defects; Neurulation; Risk Factors
PubMed: 25032496
DOI: 10.1146/annurev-neuro-062012-170354 -
Birth Defects Research Nov 2019Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD... (Review)
Review
Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD pathogenesis has not yet been fully elucidated, many risk factors, both genetic and environmental, have been extensively reported. Classically divided in two main sub-groups (open and closed defects) NTDs present extremely variable prognosis mainly depending on the site of the lesion. Herein, we review the literature on the histological and pathological features, epidemiology, prenatal diagnosis, and prognosis, based on the type of defect, with the aim of providing important information based on NTDs classification for clinicians and scientists.
Topics: Anencephaly; Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 30421543
DOI: 10.1002/bdr2.1380 -
Cell May 2023Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely...
Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely unknown due to prohibitions on human embryo research and limitations of available model systems. Here, we establish a three-dimensional (3D) prolonged in vitro culture (pIVC) system supporting cynomolgus monkey embryo development from 7 to 25 days post-fertilization. Through single-cell multi-omics analyses, we demonstrate that pIVC embryos form three germ layers, including primordial germ cells, and establish proper DNA methylation and chromatin accessibility through advanced gastrulation stages. In addition, pIVC embryo immunofluorescence confirms neural crest formation, NT closure, and neural progenitor regionalization. Finally, we demonstrate that the transcriptional profiles and morphogenetics of pIVC embryos resemble key features of similarly staged in vivo cynomolgus and human embryos. This work therefore describes a system to study non-human primate embryogenesis through advanced gastrulation and early neurulation.
Topics: Animals; Humans; Blastocyst; Embryo, Mammalian; Embryonic Development; Macaca fascicularis; Neural Tube Defects; Neurulation; Tissue Culture Techniques
PubMed: 37172562
DOI: 10.1016/j.cell.2023.04.019 -
Trends in Neurosciences Jul 2020Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of... (Review)
Review
Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of the CNS. Following mandatory folic acid fortification of dietary grains, a dramatic reduction in the incidence of NTDs was observed in areas where the policy was implemented, yet the genetic drivers of NTDs in humans, and the mechanisms by which folic acid prevents disease, remain disputed. Here, we discuss current understanding of human NTD genetics, recent advances regarding potential mechanisms by which folic acid might modify risk through effects on the epigenome and transcriptome, and new approaches to study refined phenotypes for a greater appreciation of the developmental and genetic causes of NTDs.
Topics: Folic Acid; Humans; Neural Tube Defects
PubMed: 32423763
DOI: 10.1016/j.tins.2020.04.009 -
The Lancet. Neurology Aug 2013Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding... (Review)
Review
Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.
Topics: Animals; Databases, Factual; Disease Models, Animal; Folic Acid; Genetic Predisposition to Disease; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Neural Tube Defects
PubMed: 23790957
DOI: 10.1016/S1474-4422(13)70110-8 -
Taiwanese Journal of Obstetrics &... Sep 2007Iniencephaly is characterized by a variable deficit of the occipital bones, resulting in an enlarged foramen magnum; partial or total absence of cervical and thoracic... (Review)
Review
Iniencephaly is characterized by a variable deficit of the occipital bones, resulting in an enlarged foramen magnum; partial or total absence of cervical and thoracic vertebrae with an irregular fusion of those present, accompanied by incomplete closure of the vertebral arches and/or bodies; significant shortening of the spinal column due to marked lordosis and hyperextension of the malformed cervicothoracic spine; and an upward-turned face and mandibular skin directly continuous with that of the chest due to the lack of neck. This article provides a comprehensive review of the reported cases of prenatally detected iniencephaly, including prenatal diagnosis, associated malformations, associated chromosomal abnormalities, and differential diagnosis. Prenatal diagnosis of a neural tube defect involving a body defect in the occiput and rachischisis of the cervical and thoracic spine with retroflexion of the head should raise the suspicion of iniencephaly. Iniencephaly may be associated with craniorachischisis and other structural anomalies. Prenatal diagnosis of non-isolated iniencephaly and craniorachischisis should alert one to the possibility of chromosomal abnormalities and prompt a cytogenetic investigation.
Topics: Diagnosis, Differential; Female; Fetal Diseases; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis
PubMed: 17962097
DOI: 10.1016/S1028-4559(08)60021-2 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Nov 2021To review the research progress on etiology and pathogenesis of spina bifida. (Review)
Review
OBJECTIVE
To review the research progress on etiology and pathogenesis of spina bifida.
METHODS
By consulting relevant domestic and foreign research literature on spina bifida, the classification, epidemic trend, pathogenesis, etiology, prevention and treatment of it were analyzed and summarized.
RESULTS
Spina bifida, a common phenotype of neural tube defects, is classified based on the degree and pattern of malformation associated with neuroectodermal involvement and is due to the disturbance of neural tube closure 28 days before embryonic development. The prevalence of spina bifida varies greatly among different ethnic groups and regions, and its etiology is complex. Currently, some spina bifida patients can be prevented by folic acid supplements, and with the improvement of treatment technology, the short-term and long-term survival rate of children with spina bifida has improved.
CONCLUSION
The research on the pathogenesis of spina bifida will be based on the refined individual information on exposure, genetics, and complex phenotype, and will provide a theoretical basis for improving prevention and treatment strategies through multidisciplinary cooperation.
Topics: Female; Folic Acid; Humans; Neural Tube Defects; Pregnancy; Prevalence; Spinal Dysraphism
PubMed: 34779160
DOI: 10.7507/1002-1892.202106052 -
Genesis (New York, N.Y. : 2000) Nov 2021Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex... (Review)
Review
Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex involving the interplay of genetic and environmental factors. Since nutrient deficiency is a risk factor and dietary changes are the major preventative measure to reduce the risk of NTDs, a more detailed understanding of how common micronutrient imbalances contribute to NTDs is crucial. While folic acid has been the most discussed environmental factor due to the success that population-wide fortification has had on prevention of NTDs, folic acid supplementation does not prevent all NTDs. The imbalance of several other micronutrients has been implicated as risks for NTDs by epidemiological studies and in vivo studies in animal models. In this review, we highlight recent literature deciphering the multifactorial mechanisms underlying NTDs with an emphasis on mouse and human data. Specifically, we focus on advances in our understanding of how too much or too little retinoic acid, zinc, and iron alter gene expression and cellular processes contributing to the pathobiology of NTDs. Synthesis of the discussed literature reveals common cellular phenotypes found in embryos with NTDs resulting from several micronutrient imbalances. The goal is to combine knowledge of these common cellular phenotypes with mechanisms underlying micronutrient imbalances to provide insights into possible new targets for preventative measures against NTDs.
Topics: Animals; Gene-Environment Interaction; Humans; Micronutrients; Neural Tube Defects
PubMed: 34665506
DOI: 10.1002/dvg.23455 -
Saudi Medical Journal Dec 2014Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant... (Review)
Review
Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant death, or significant lifelong handicaps. The malformations result from failure of the neural folds to fuse in the midline, and form the neural tube between the third and the fourth week of embryonic development. This review article discusses their classification, clinical features, and genetics. Most NTDs are sporadic and both genetic, and non-genetic environmental factors are involved in its etiology. Consanguinity was suggested to contribute to the high incidence of NTDs in several countries, including Saudi Arabia. Syndromes, often associated with chromosomal anomalies, account for <10% of all NTDs; but a higher proportion (20%) has been documented in Saudi Arabia. Genetic predisposition constitutes the major underlying risk factor, with a strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity.
Topics: Consanguinity; Humans; Infant, Newborn; Methylenetetrahydrofolate Reductase (NADPH2); Neural Tube Defects
PubMed: 25551113
DOI: No ID Found -
Journal of Pediatric Rehabilitation... Dec 2017It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes... (Review)
Review
It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.
Topics: Europe; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Molecular Epidemiology; Neural Tube Defects; United States; Exome Sequencing; Whole Genome Sequencing
PubMed: 29125517
DOI: 10.3233/PRM-170456