Human neural tube defects: Developmental biology, epidemiology, and genetics

Detrait, Eric; George, Timothy M.; Etchevers, Heather C.; Gilbert, John R.; Vekemans, Michel; Speer, Marcy C.

doi:10.1016/j.ntt.2004.12.007

Cited by 328 publications

(301 citation statements)

References 88 publications

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“…Subsequent development, together with vesiculation within the tube, gives rise to the brain and spinal cord. Further details of this complex process are beyond the scope of this review (for reviews, see REFS 4,5 ).…”

Section: Neurulation and Neural Tube Defectsmentioning

confidence: 99%

Neural tube defects and folate: case far from closed

Shaw²,

et al. 2006

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Neural tube closure takes place during early embryogenesis and requires interactions between genetic and environmental factors. Failure of neural tube closure is a common congenital malformation that results in morbidity and mortality. A major clinical achievement has been the use of periconceptional folic acid supplements, which prevents ~50-75% of cases of neural tube defects. However, the mechanism underlying the beneficial effects of folic acid is far from clear. Biochemical, genetic and epidemiological observations have led to the development of the methylation hypothesis, which suggests that folic acid prevents neural tube defects by stimulating cellular methylation reactions. Exploring the methylation hypothesis could direct us towards additional strategies to prevent neural tube defects.Neural tube defects (NTDs) are complex congenital malformations of the CNS. Anencephaly and spina bifida are the most common and severe forms of NTD, with a prevalence of about 1 in 1,000 births, although this varies throughout the world 1 . Infants with anencephaly are stillborn or die shortly after birth, whereas infants with spina bifida can survive but are likely to have severe lifelong disabilities and are at risk of psychosocial maladjustment. The estimated lifetime medical costs are high; for example, in California, USA, the costs for children born with spina bifida exceed US$81 million per year 2 .It has been known for more than 20 years that women can reduce their risk of having an NTDaffected pregnancy by taking folic acid supplements. However, the underlying mechanisms byCorrespondence to H.J.B. H.Blom@cukz.umcn.nl. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Neurosci. Author manuscript; available in PMC 2010 November 2. Neurulation and neural tube defectsNeurulation has long fascinated scientists, as evidenced by a devoted literature that extends back hundreds of years. The process of neurulation occurs during early embryogenesis, starting with the formation of the neural plate from specialized ectodermal cells and culminating in the closure of the neural tube (FIG. 1), the precursor of both the CNS and most of the PNS. Considered most simply, the neural plate develops bilateral neural folds, which elevate and fuse at the midline to create the neural tube. Subsequent development, together with vesiculation within the tube, gives rise to the brain and spinal cord. Further details of this complex process are beyond the scope of this review (for reviews, see REFS 4,5 ).Neurulation seems to be highly complex and tightly regulated. The development and closure of the neural tube is usually completed by 28 days post-conception. This means that by the time a woman finds out that she is pregnant, the neural tube is almost completely closed. For the neural tube to close properly, genes that regulate various morphogenetic activities must function cooperatively. These activities include programmed cell death, neural crest...

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Section: Neurulation and Neural Tube Defectsmentioning

confidence: 99%

Neural tube defects and folate: case far from closed

Shaw²,

et al. 2006

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“…A vast number of clinical studies have established that folate is a prominent environmental factor needed for appropriate neural tube closure (Detrait et al, 2005;MRC Vitamin Study Research Group, 1991;Pitkin, 2007). Low blood folate levels in pregnant women are correlated with higher risk of NTDs in their offspring (Detrait et al, 2005;Smithells et al, 1976) and periconceptional supplementation of folate decreases the recurrence and occurrence of NTDs (MRC Vitamin Study Research Group, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Low blood folate levels in pregnant women are correlated with higher risk of NTDs in their offspring (Detrait et al, 2005;Smithells et al, 1976) and periconceptional supplementation of folate decreases the recurrence and occurrence of NTDs (MRC Vitamin Study Research Group, 1991).…”

Section: Introductionmentioning

confidence: 99%

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

2017

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Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs.

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“…Spina bifida is the second most common congenital birth defect worldwide, 1 caused by failure of closure of the neural tube during the early weeks of gestation. Long-term problems related to the disorder include ambulatory difficulties, bowel and bladder incontinence, hydrocephalus and shunt malfunction, skin breakdown and learning difficulties.…”

Section: Introductionmentioning

confidence: 99%

Predictors of parenting stress in mothers of children with spina bifida

et al. 2010

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Study design: Prospective cross-sectional multidimensional study using clinical assessment and standard measures. Objectives: To determine the medical and social factors associated with parenting stress among mothers of children with spina bifida. Setting: Spina bifida clinics of two tertiary hospitals in urban Kuala Lumpur, Malaysia. Methods: A total of 81 mothers of children aged 1-18 years completed the Parenting Stress IndexShort Form (PSI/SF). Each child's adaptive skills were assessed using the Vineland Adaptive Behaviour Scales (VABS), Interview Edition. Medical and social data were obtained from direct interviews and case note reviews. Hierarchical multiple regression analysis was used to investigate factors that were determinants for high scores in the parental distress (PD), difficult child (DC) and parent-child dysfunctional interaction (P-CDI) subdomains of the PSI/SF. Results were expressed as beta coefficient (b) and 95% confidence intervals (95% CIs). Results: Single-parent families (b 8.6, 95% CI 3.4-13.9) and the need for clean intermittent catheterization of bladder (b 3.5, 95% CI 0.7-6.2) were associated with high PD scores. Clean intermittent catheterization (b 3.0, 95% CI 0.5-5.5) was associated with higher DC scores. Lower composite VABS scores (b À0.08, 95% CI À0.02 to À0.15) and mother as the sole caregiver (b 2.6, 95% CI 0.15-4.96) was associated with higher P-CDI scores. Conclusion: The need for clean intermittent catheterization was the only medical factor associated with parenting stress in mothers of children with spina bifida. This was mediated by single parenthood, caregiver status and the child's adaptive skills.

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Human neural tube defects: Developmental biology, epidemiology, and genetics

Cited by 328 publications

References 88 publications

Neural tube defects and folate: case far from closed

Neural tube defects and folate: case far from closed

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

Predictors of parenting stress in mothers of children with spina bifida

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