Spina bifida and pediatric cancers.
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ABSTRACT:
SUBMITTER: Heck JE
PROVIDER: S-EPMC7577564 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60-70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa.
| S-EPMC4898641 | biostudies-other
Project description:Genome wide DNA methylation profiling of 10 patients with myelomeningocele (MMC) and 6 healthy controls
2016-10-03 | GSE81846 | GEO
Project description:PURPOSE:Achieving bladder continence in individuals with spina bifida is a lifetime management goal. We investigated bladder continence status through time and factors associated with this status in patients with spina bifida. MATERIALS AND METHODS:We used National Spina Bifida Patient Registry data collected from 2009 through 2015 and applied generalized estimating equation models to analyze factors associated with bladder continence status. RESULTS:This analysis included 5,250 participants with spina bifida in a large, multi-institutional patient registry who accounted for 12,740 annual clinic visit records during the study period. At last followup mean age was 16.6 years, 22.4% of participants had undergone bladder continence surgery, 92.6% used some form of bladder management and 45.8% reported bladder continence. In a multivariable regression model the likelihood of bladder continence was significantly greater in those who were older, were female, were nonHispanic white, had a nonmyelomeningocele diagnosis, had a lower level of lesion, had a higher mobility level and had private insurance. Continence surgery history and current management were also associated with continence independent of all other factors (adjusted OR and 95% CI 1.9, 1.7-2.1 and 3.8, 3.2-4.6, respectively). The association between bladder management and continence was stronger for those with a myelomeningocele diagnosis (adjusted OR 4.6) than with nonmyelomeningocele (adjusted OR 2.8). CONCLUSIONS:In addition to demographic, social and clinical factors, surgical intervention and bladder management are significantly and independently associated with bladder continence status in individuals with spina bifida. The association between bladder management and continence is stronger in those with myelomeningocele.
| S-EPMC5948157 | biostudies-literature
Project description:Key content:Spina bifida is a congenital neurological condition with lifelong physical and mental effects.Open fetal repair of the spinal lesion has been shown to improve hindbrain herniation, ventriculoperitoneal shunting, independent mobility and bladder outcomes for the child and, despite an increased risk of prematurity, does not seem to increase the risk of neurodevelopmental impairment.Open fetal surgery is associated with maternal morbidity.Surgery at our institution is offered and performed according to internationally agreed criteria and protocols.Further evidence regarding long-term outcomes, fetoscopic repair and alternative techniques is awaited. Learning objectives:To understand the clinical effects, potential prevention and prenatal diagnosis of spina bifida.To understand the rationale and evidence supporting the benefits and risks of fetal repair of open spina bifida.To understand the criteria defining those who are likely to benefit from fetal surgery. Ethical issues:The concept of the fetus as a patient, and issues surrounding fetal death or the need for resuscitation during fetal surgery.The associated maternal morbidity in a procedure performed solely for the benefit of the fetus/child.The financial implications of new surgical treatments.
| S-EPMC6876677 | biostudies-literature
Project description:BackgroundA National Spina Bifida Patient Registry (NSBPR) was begun in 2009 to help understand the natural history of spina bifida (SB) and the effects of treatments provided by SB clinics. We used the NSBPR to explore the relationship of sociodemographic characteristics with SB outcomes.MethodsUsing NSBPR data collected in 2009 to 2012, we examined the unadjusted association between demographic characteristics and 4 SB outcomes: bowel continence, bladder continence, mobility, and presence of pressure sores. We then developed multivariable logistic models to explore these relationships while controlling for SB clinic, SB type, and level of lesion.ResultsData were available on 2054 patients <22 years of age from 10 SB clinics. In the multivariable models, older age groups were more likely to have continence and pressure sores and less likely to be community ambulatory. Males and patients without private insurance were less likely to be continent and community ambulatory. Non-Hispanic blacks were less likely to be continent. Level of lesion was associated with all outcomes; SB type was associated with all but pressure sores; and all outcomes except community ambulation showed significant variation across clinic sites.ConclusionsSociodemographic attributes are associated with SB outcomes. In particular, males, non-Hispanic blacks, and patients without private insurance have less favorable outcomes, and age has an impact as well. These characteristics need to be considered by clinicians who care for this patient population and factored into case-mix adjustment when evaluating variation in clinical and functional outcomes among different SB clinics.
| S-EPMC4536568 | biostudies-literature
Project description:BACKGROUND:Aim of our study was to evaluate degree of genetic homozygosity in male and female gender of spina bifida (SB) occulta and SB aperta patients. PATIENTS AND METHODS:We evaluated 95 patients with SB occulta and 51 with SB aperta. Degree of genetic homozygosity was evaluated by direct observation of 15 homozygously recessive characteristics (HRC) by HRC-test separately for SB occulta and SB aperta participants. Additionally 370 individuals without SB from Serbia were randomly selected and evaluated as control group. Male and female gender was separately evaluated for assessing degree of genetic homozygosity. RESULTS:There was no significant difference in mean values of HRC between male and female gender in control group (male gender -3.9±1.2, female gender -4.0±1.4, z=0.39; p>0.05), SB occulta (male gender -4.1±1.5, female gender -4.7±1.4, z=1.87, p>0.05) and SB aperta patients (male gender -4.3±1.6, female gender -4.5±1.4, z=0.66, p>0.05), while there was significantly increased recessive homozygosity in female SB occulta group versus control female group (Females: SB occulta -4.7±1.4, Control group -4.0±1.4, z=3.16, p<0.01) and female SB aperta group versus control female group (Females: SB aperta -4.5±1.4, Control group -4.0±1.4, z=2.05, p<0.05). CONCLUSION:There is increased recessive homozygosity in tested female SB occulta and female SB aperta individuals versus SB male participants and significantly increased recessive homozygosity in female groups of SB patients versus control female group. These findings could lead to the possible assumption that different genes in different degree might be expressed in SB occulta and SB aperta patients.
| S-EPMC3738390 | biostudies-literature
Project description:IntroductionAssuming that spina bifida (SB) is a genetically controlled disease, the aim of our study was to evaluate the degree of genetic homozygosity and the distribution of AB0 blood types among patients with SB occulta and SB aperta by the homozygously recessive characteristics (HRC) test.Material and methodsOur study included an analysis of the presence, distribution and individual combination of 15 selected genetically controlled morpho-physiological traits in a sample of 100 patients with SB (SB occulta N = 50 and SB aperta N = 50) and a control group of individuals (N = 100).ResultsWe found a statistically significant difference between the mean values for genetic homozygosity (SB 4.5 ±0.3; control 3.0 ±0.2, p < 0.001) and also differences in the presence of certain individual combinations of such traits. In 12 (80.0%) of the 15 observed characteristics, recessive homozygosity was expressed to a greater degree among the group of SB patients, while for 9 (60.0%) of the traits this level of difference was statistically significant (Σ(χ) (2) = 266.3, p < 0.001). There was no difference in average homozygosity of such genetic markers between groups of SB occulta and SB aperta patients, but the type of individual variation in the two studied groups significantly differed. In the group of patients with SB the frequency of 0 blood group was significantly increased while B blood group was significantly decreased.ConclusionsOur results clearly show that there is a populational genetic difference in the degree of genetic homozygosity and variability between the group of patients with SB and individuals without clinical manifestations, indicating a possible genetic component in the aetiopathogenesis of spina bifida.
| S-EPMC3302695 | biostudies-literature
Project description:OBJECTIVE:To determine rates and types of peripartum morbidity among delivering women with spina bifida (SB) compared to those without SB. The rates of pregnancy and delivery among women with SB have been significantly increasing. Current knowledge of peripartum outcomes for these women is limited. METHODS:Using 2004-2013 National Inpatient Sample data, we identified all hospitalizations for delivery, distinguishing between women with and without SB. Using a code-based algorithm, we determined whether a complication occurred during the hospitalization. We then fit a series of multivariable logistic models to examine for associations between a complication occurrence during vaginal or cesarean delivery and a woman's SB status. RESULTS:We identified 38,319,814 weighted admissions for delivery, 9516 of which were made by women with SB. Women with SB had a significantly higher rate of cesarean delivery than women without this diagnosis (53% vs 32%, P < .001). The 46.7% of women with SB who delivered vaginally did not have significantly increased odds of a complication associated with their delivery compared to women without SB [odds ratio 1.15, 95% confidence interval 0.99-1.34, P = .066]. However, women with SB who underwent a cesarean delivery did have higher odds of morbidity compared to those without (odds ratio 1.49, 95% confidence interval 1.25-1.78, P < .001). Common complications included preterm delivery, urinary tract infection, hematologic event, and blood transfusion. CONCLUSION:Compared to women without SB, those with SB deliver more frequently by cesarean section and have higher odds of morbidity associated with cesarean delivery, but not vaginal delivery.
| S-EPMC6522127 | biostudies-literature
Project description:Several single-nucleotide variants (SNVs) in low-density lipoprotein receptor-related protein 6 (Lrp6) cause neural tube defects (NTDs) in mice. We therefore examined LRP6 in 192 unrelated infants from California with the NTD, spina bifida, and found four heterozygous missense SNVs, three of which were predicted to be deleterious, among NTD cases and not in 190 ethnically matched nonmalformed controls. Parents and siblings could not be tested because of the study design. Like Crooked tail and Ringleschwanz mouse variants, the p.Tyr544Cys Lrp6 protein failed to bind the chaperone protein mesoderm development and impaired Lrp6 subcellular localization to the plasma membrane of MDCK II cells. Only the p.Tyr544Cys Lrp6 variant downregulated canonical Wnt signaling in a TopFlash luciferase reporter in vitro assay. In contrast, three Lrp6 mutants (p.Ala3Val, p.Tyr544Cys, and p.Arg1574Leu) increased noncanonical Wnt/planar cell polarity (PCP) signaling in an Ap1-luciferase assay. Thus, LRP6 variants outside of YWTD repeats could potentially predispose embryos to NTDs, whereas Lrp6 modulation of Wnt/PCP signaling would be more essential than its canonical pathway role in neural tube closure.
| S-EPMC4361299 | biostudies-literature
Project description:Spina bifida is one of the most common neural tube defects (NTDs) with a complex etiology. Variants in planar cell polarity (PCP) genes have been associated with NTDs including spina bifida in both animal models and human cohorts. In this study, we sequenced all exons of CELSR1 in 192 spina bifida patients from a California population to determine the contribution of CELSR1 mutations in the studied population. Novel and rare variants identified in these patients were subsequently genotyped in 190 ethnically matched control individuals. Six missense mutations not found in controls were predicted to be deleterious by both SIFT and PolyPhen. Two TG dinucleotide repeat variants were individually detected in 2 spina bifida patients but not detected in controls. In vitro functional analysis showed that the two TG dinucleotide repeat variants not only changed subcellular localization of the CELSR1 protein, but also impaired the physical association between CELSR1 and VANGL2, and thus diminished the ability to recruit VANGL2 for cell-cell contact. In total, 3% of our spina bifida patients carry deleterious or predicted to be deleterious CELSR1 mutations. Our findings suggest that CELSR1 mutations contribute to the risk of spina bifida in a cohort of spina bifida patients from California.
| S-EPMC3954890 | biostudies-literature