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:Neural tube defects (NTDs) are a group of severe congenital malformations caused by a failure of neural tube closure during early embryonic development. Although extensively investigated, the genetic etiology of NTDs remains poorly understood. FKBP8 is critical for proper mammalian neural tube closure. Fkbp8-/- mouse embryos showed posterior NTDs consistent with a diagnosis of spina bifida (SB). To date, no publication has reported any association between FKBP8 and human NTDs. Using Sanger sequencing on genomic DNA samples from 472 SB and 565 control samples, we identified five rare (MAF ≤ 0.001) deleterious variants in SB patients, while no rare deleterious variant was identified in the controls (P = 0.0191). p.Glu140* affected FKBP8 localization to the mitochondria and created a truncated form of the FKBP8 protein, thus impairing its interaction with BCL2 and ultimately leading to an increase in cellular apoptosis. p.Ser3Leu, p.Lys315Asn and p.Ala292Ser variants decreased FKBP8 protein level. p.Lys315Asn further increased the cellular apoptosis. RNA sequencing on anterior and posterior tissues isolated from Fkbp8-/- and wildtype mice at E9.5 and E10.5 showed that Fkbp8-/- embryos have an abnormal expression profile within tissues harvested at posterior sites, thus leading to a posterior NTD. Moreover, we found that Fkbp8 knockout mouse embryos have abnormal expression of Wnt3a and Nkx2.9 during the early stage of neural tube development, perhaps also contributing to caudal specific NTDs. These findings provide evidence that functional variants of FKBP8 are risk factors for SB, which may involve a novel mechanism by which Fkbp8 mutations specifically cause SB in mice.
| S-EPMC7645715 | biostudies-literature
Project description:Renal damage and renal failure are among the most severe complications of spina bifida. Over the past decades, a comprehensive treatment strategy has been applied that results in minimal renal scaring. In addition, the majority of patients can be dry for urine by the time they go to primary school. To obtain such results, it is mandatory to treat detrusor overactivity from birth onward, as upper urinary tract changes predominantly start in the first months of life. This means that new patients with spina bifida should be treated from birth by clean intermittent catheterization and pharmacological suppression of detrusor overactivity. Urinary tract infections, when present, need aggressive treatment, and in many patients, permanent prophylaxis is indicated. Later in life, therapy can be tailored to urodynamic findings. Children with paralyzed pelvic floor and hence urinary incontinence are routinely offered surgery around the age of 5 years to become dry. Rectus abdominis sling suspension of the bladder neck is the first-choice procedure, with good to excellent results in both male and female patients. In children with detrusor hyperactivity, detrusorectomy can be performed as an alternative for ileocystoplasty provided there is adequate bladder capacity. Wheelchair-bound patients can manage their bladder more easily with a continent catheterizable stoma on top of the bladder. This stoma provides them extra privacy and diminishes parental burden. Bowel management is done by retrograde or antegrade enema therapy. Concerning sexuality, special attention is needed to address expectations of adolescent patients. Sensibility of the glans penis can be restored by surgery in the majority of patients.
| S-EPMC2335291 | biostudies-literature