Degree of genetic homozygosity and distribution of AB0 blood types among patients with spina bifida occulta and spina bifida aperta

Introduction

Assuming 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 methods

Our 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).

Results

We 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.

Conclusions

Our 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.     

CT-VRT重建技术对腰骶部隐性脊柱裂的诊断价值

目的评估CT容积漫游技术（CT-VRT）重建对腰骶部隐性脊柱裂（SBO）的诊断价值。方法回顾性分析212例腰骶部隐性脊柱裂的骨盆X线平片和CT-VRT的影像特征,包括对称性、形态、范围和受累椎体及脊柱节段,并比较两种检查手段对骨质缺如的影像特征的显示情况。结果在显示SBO对称性、形态、范围、受累椎体及脊柱节段和游离骨脊等方面,CT-VRT比X线平片准确（P〈0.05）;对于其他影像特征的显示CT-VRT和X线平片无明显差异（P〉0.05）。结论 X线平片和CT是检查SBO的有效手段,CT-VRT能够直观、立体、更准确的显示SBO形态、范围和受累椎体及脊柱节段,鉴别真、假裂隙样骨质缺如,并进一步确定假裂隙样骨质缺失的本质。     

Spinal dysraphia as an autosomal dominant defect in four families

Four families were selected randomly on the basis of the occurrence of spina bifida cystica and/or spina bifida occulta in one or more family members. Sixty-three relatives were studied clinically and roentgenologically; their roentgenograms were evaluated blindly. Twenty-eight were clinically and roentgenologically normal; 35 were diagnosed as having spina bifida occulta (SBO), spina bifida cystica (SBC), vertebral anomalies, and/or external defects usually interpreted as evidence for SBO. Excluding one proband we found the frequency of SBO to be 19/51 (37%) and the frequency of all types of spinal/vertebral defects (excluding five probands) to be 30/58 (52%). The distribution of these defects in the four families was analyzed using likelihood methods corrected for random ascertainment. The log likelihood values for sporadic, recessive, and dominant models were ?26.69, ?20.95, and ?18.90, respectively, indicating a higher likelihood of autosomal dominant inheritance than sporadic occurrence or recessive inheritance. The penetrance probability in this dominant model, estimated by maximum likelihood, is 0.749 ± 0.100. Further examination of these data suggests that SBO and SBC represent different expressions of the same dominant gene in these kindreds.     

Latex allergy in spina bifida patients – prevention by primary prophylaxis

Background The effect of latex prophylaxis has not been investigated in spina bifida children, a high-risk group for latex allergy. As repeated operations have been identified as a major cause of latex sensitization, we wanted to find out whether primary latex prophylaxis during surgery could prevent latex allergy in children with spina bifida.
Methods In December 1995, we established latex-free surgery and anesthesia for all patients with spina bifida regardless of their sensitization to latex. Twelve children born after that date (mean age 1.2 years, mean ntmiber of operations 3.3, range 1 -7) were tested for specific IgE against latex until December 1997 (ImmunoCap, Pharmacia, Uppsala, Sweden) and compared with eight children born before December 1995 (mean age 1.3 years, mean number of operations 3.6, range 1–8), in whom a test for latex IgE had been done before the age of 2 years.
Results Before we established primary prophylaxis, three of seven children with spina bifida (38%) were sensitized to latex until the age of 2 years. After the establishment of a latex-free operating theater for spina bifida patients, none of the 12 patients were sensitized to latex despite up to seven operations in each child.
Conclusions Primary latex prophylaxis during surgery can prevent latex sensitization in young spina bifida patients.     

Goal-Directed Behavior and Perception of Self-Competence in Children with Spina Bifida

Compared a group of school-age children with spina bifida (n= 75) between the ages of 6 and 12 years with an age- and IQ-matchedcontrol group of normal children (n = 15). As predicted, thespina bifida children spent less time using goal-directed behaviorsand more time in simple manipulation of the toys compared tothe normal children. There were no group differences betweenthe spina bifida and normal children's perceived competencebut parents of the spina bifida children rated their childrenas having lower cognitive and physical competence. Associationswere found between goal-directed behaviors and perceived self-competencefor children in the spina bifida group but not the normal group.     

Risk factors for latex allergy in patients with spina bifida

Objective and methods In order to study risk factors for latex allergy in patients with spina bifida, we investigated 165 patients with spina bifida (mean age 9 years). Besides answering a questionnaire, patients underwent skin-prick testing and determination of specific serum IgE to latex as well as a screening test for specific IgE to environmental allergens. A total of 80 patients(49%) were sensitized to latex according to the presence of specific IgE to latex. Results Skin-prick tests (SPT) with high ammonia latex milk were performed in 81 of our patients with spina bifida and were positive in 36 patients (46%). Concordance of SPT with specific IgE in serum was good. Nineteen out of 165 patients suffered from a clinically relevant latex allergy: five patients had a history of systemic reactions to latex (e.g. severe bronchospasm, anaphylactic reactions), mostly during surgery. Fourteen patients reported clinical symptoms while inflating a balloon; all these 19 patients were sensitized to latex. Number of operations ranged from one to 26 (mean 5 operations). Concentration of specific IgE to latex in serum correlated well with increasing numbers of operations. Some 32/76 patients (41%) with spina bifida who were sensitized to latex showed an atopic disposition, while 21 out of 81 latex-negative patients (26%) were atopic. Of 300 consecutive sera (mean age of patients 9 years) sent to our laboratory for routine determination of specific IgE, 144 (48%) were positive in terms of specific IgE to environmental allergens, of which 247144 (17%) were sensitized to latex. Conclusions From our data we conclude that in order to minimize risk of severe systemic clinical reactions, all patients with spina bifida should be screened for their individual risk of latex allergy to plan preventive measures before operations. Main risk factors for latex allergy seem to be: more than five operations, atopic predisposition, history of clinical symptoms while inflating a balloon, and a sensitization with a CAP-class of ± 4.     

Brief report: testing the factorial invariance of the CBCL Somatic Complaints scale as a measure of internalizing symptoms for children with and without chronic illness

OBJECTIVE: To examine the factorial invariance of the Somatic Complaints subscale of the Child Behavior Checklist as a measure of Internalizing Behavior Problems across a sample of children with and without spina bifida. METHODS: Multisample confirmatory factor analysis was used to compare mother and father report on the Somatic Complaints subscale across a sample of children with spina bifida and a matched comparison sample of able-bodied children ages 8 through 11 years (N = 68 for mother report in each group; N = 54 for father report in the spina bifida group and 53 for the able-bodied group). RESULTS: Although there were no significant between-group differences in the magnitude of factor loadings, significantly more variance in scores on the Somatic Complaints scale was unrelated to Internalizing Behavior Problems for the spina bifida group, compared to the able-bodied group. There were no between-group differences when father data were analyzed, but the latent variable of Internalizing Behavior Problems explained little variance in the Somatic Complaints scale for either group. CONCLUSIONS: Maternal report of Somatic Complaints on the CBCL does not appear to measure Internalizing Behavior Problems in the same manner across groups of children with and without spina bifida. This suggests that the Somatic Complaints subscale should be interpreted with caution when measuring Internalizing Behavior Problems within this population.     

Possible X-linked anencephaly and spina bifida—report of a kindred

Causal heterogeneity of anencephaly and spina bifida has been demonstrated; in rare families the neural tube defect may be caused by a single gene. We report a family in which four cases of anencephaly or spina bifida may represent X-linked inheritance.     

The search of latex sensitization in spina bifida: diagnostic approach

BACKGROUND: Sensitization to latex has become a major problem in children with spina bifida. Life-threatening reactions may occur in these patients, therefore the search of latex sensitization must be an active task in all of these children. OBJECTIVE: To design an approach for the diagnosis of latex sensitization in children with spina bifida. METHODS: We studied 100 consecutive unselected patients. Skin prick tests with a commercial latex extract were performed, latex-specific serum immunoglobulin (Ig) E was determined by CAP test, and risk factors were studied. Originally, patients with an area of latex skin test > 50% of the area of histamine and/or CAP class > or = 3 were considered sensitized to latex. Diagnostic tests were also performed in a control group of 51 atopic and nonatopic children. RESULTS: After performing a receiver-operating characteristics curve for both tests we recommend skin tests > 25% of the area of histamine (sensitivity - SEN = 79%, specificity - SPE = 100%, positive predictive value - PPV = 100%, negative predictive value - NPV = 90%), or CAP class > or = 2 (SEN = 88%, SPE = 100%, PPV = 100%, NPV = 94%) as diagnostic cut-off points. The anamnesis had a SEN of 44% for diagnosis, and a SPE of 100%. Latex sensitization was associated with more than 5 operations (OR = 8, 95% CI = 3-21.3), a personal history of atopy (OR = 11.5, 95% CI = 2.3-57.1), and serum total IgE > or = 2 z-units (OR = 4, 95% CI = 1. 6-10). CONCLUSION: For the routine evaluation of children with spina bifida, we propose a diagnostic algorithm with skin prick tests as a first step and CAP second.     

Genetic susceptibility to neural tube defect pregnancy varies with offspring phenotype

Neural tube defects (NTDs) have a well-established genetic basis, although no single genetic factor has been identified as a major risk factor in NTD susceptibility. A large number of association studies have been conducted to investigate the possibility that NTD susceptibility is linked to polymorphic variation in genes involved in early embryonic development or in the absorption or metabolism of folate, a nutrient that has been clearly associated with a reduction in the risk of NTD pregnancy. A study of three candidate gene polymorphisms at loci implicated in folate absorption and metabolism has been conducted on a population of 211 mothers of a heterogeneous mix of NTD phenotypes: 59% spina bifida aperta (SBA), 20.3% spina bifida occulta (SBO), 17% anencephaly, and 3.7% other NTD. Allele and genotype frequencies were stratified according to offspring NTD phenotype, and variation in the level of NTD risk was associated with different phenotypes. All the three variants (MTHFR 677C > T, GCPII 1561C > T, and RFC-1 80G > A) were shown to significantly influence the risk of anencephalic pregnancy. In addition, the MTHFR 677C > T variant conferred a modest protective effect in SBO mothers and the total NTD mother group, but not in SBA mothers. The RFC-1 80G > A variant elevated the risk of SBO and anencephalic pregnancy. The findings of this study suggest that NTD phenotypic heterogeneity may help explain the mixed findings of previous association studies and that different polymorphisms may hold differing degrees of significance for the various NTD phenotypes.     

Neuroependymal denudation is in progress in full-term human foetal spina bifida aperta

In human spina bifida aperta (SBA), cerebral pathogenesis [hydrocephalus, Sylvius aqueduct (SA) stenosis and heterotopias] is poorly understood. In animal models, loss of ventricular lining (ependymal denudation) causes SA stenosis and hydrocephalus. We aimed to investigate whether ependymal denudation also takes place in human foetal SBA. Considering that ependymal denudation would be related to alterations in junction proteins, sections through SA of five SBA and six control foetuses (gestational ages ranged between 37 and 40 weeks) were immunostained for markers of ependyma (caveolin 1, βIV-tubulin, S100), junction proteins (N-cadherin, connexin-43, neural cell adhesion molecule (NCAM), blood vessels (Glut-1) and astrocytes [glial fibrillary acidic protein (GFAP)]. In control foetuses, ependymal denudation was absent. In SBA foetuses different stages of ependymal denudation were observed: (i) intact ependyma/neuroepithelium; (ii) imminent ependymal denudation (with abnormal subcellular location of junction proteins); (iii) ependymal denudation (with protrusion of neuropile into SA, formation of rosettes and macrophage invasion); (iv) astroglial reaction. It is suggested that abnormalities in the formation of gap and adherent junctions result in defective ependymal coupling, desynchronized ciliary beating and ependymal denudation, leading to hydrocephalus. The presence of various stages of ependymal denudation within the same full-term SBA foetuses suggests continuation of the process after birth.     

Radiographic method to assess the prevalence of sacral spina bifida occulta

Spina bifida occulta of the sacrum is the most common type of spinal deformity. Many authors have published data on the frequency of spina bifida occulta, with varying results. Some possible reasons for this variability could include the differing methods used to gather data and differing ways of classifying the condition. This study attempts to develop an X-ray method to study sacral spina bifida occulta in a standardized fashion, using an angulated antero-posterior technique. This technique is then used to estimate the frequency of sacral spina bifida occulta in an Australian sample. The sacra of 53 cadavers were X-rayed and the level of closure of the sacral spinal canal recorded. The X-ray technique was validated by open dissection of six of the cadavers studied and was shown to be accurate to half a sacral segment. No sacra with a completely open sacral canal were found, two sacra (4%) were open from S2 down to S5 and ten sacra (19%) were open from S3 down to S5. The most common condition (43%) recorded was where S4 and S5 only were open. Eighteen cadavers (34%) showed only S5 open, and interestingly, no sacra were recorded as having the dorsal sacral arch completely closed. A study of a larger sample will follow using the validated X-ray technique.     

Urinary bladder adenocarcinoma arising in a spina bifida patient

Urinary bladder adenocarcinomas are rare malignancies accounting for approximately 2.5% of all urothelial neoplasms. Intestinal metaplasia of the urothelium indicates the presence of intestinal-type goblet cells and was generally observed to coexist with or to precede the diagnosis of bladder adenocarcinomas. Controversy continues of whether intestinal metaplasia is an acquired precancerous lesion, secondary to different insults to the urothelium, or a concomitant lesion in glandular carcinogenesis. Patients with neurogenic bladders are particularly at risk for developing bladder cancer, mostly squamous cell carcinoma and rarely adenocarcinoma. In these patients, chronic irritation of the urothelium as well as long-term indwelling urinary catheters were the most significant risk factors. Spina bifida is a congenital developmental abnormality that may result in neurogenic bladder. There is only one previously reported case of urothelial carcinoma with associated squamous metaplasia of the bladder occurring in a spina bifida patient. We report the first case of bladder adenocarcinoma associated with intestinal metaplasia occurring in a spina bifida occulta patient. The patient had a complicated clinical course and suffered recurrent urinary tract infections, renal calculi, and urinary incontinence and was managed with intermittent as well as indwelling catheterization.     

Condition-related knowledge among children with spina bifida: longitudinal changes and predictors

OBJECTIVE: To examine changes in three domains of condition-related knowledge among youth with spina bifida and to examine the utility of youth cognitive ability level and condition severity as predictors of knowledge change. METHODS: Seventy preadolescents with spina bifida completed a 12-item questionnaire assessing knowledge of spina bifida at three time points during middle childhood and early adolescence. Specific domains of knowledge assessed included (a) etiology of spina bifida, (b) functional status, and (c) shunt functioning (completed by participants with shunted hydrocephalus only). RESULTS: Findings revealed gains in accuracy of knowledge on 6 of 12 items; however, neither children's cognitive ability level nor condition severity predicted changes in knowledge over time. Most condition domains were characterized by low-to-moderate levels of knowledge across time. CONCLUSIONS: Although significant gains were evident in children's condition-related knowledge, at Time 3, many participants still failed to understand basic information about the etiology of their condition or major functional issues associated with spina bifida. Additional education about catheterization and shunt malfunction are two domains that may be of particular clinical significance.     

Attention and executive functions in adolescents with spina bifida

OBJECTIVE: This study was designed to examine attention processes and executive functioning in adolescents with spina bifida, and to explore whether impairment in these domains contributes to problems with social adjustment. METHODS: A sample of adolescents with spina bifida (n = 68) and a matched comparison group (n = 68) and their families were followed longitudinally. All participants completed questionnaires, and the adolescent participants underwent neurocognitive testing. RESULTS: The spina bifida sample showed greater impairment on objective and subjective measures of attention and executive functioning, even when differences in intellectual functioning were controlled. Additionally, attention and executive deficits were found to be predictive of social adjustment difficulties. A mediational analysis suggested the neurocognitive deficits mediate associations between spina bifida status and social adjustment difficulties. CONCLUSIONS: Adolescents with spina bifida appear to exhibit clear impairment in attention and executive functioning and this impairment may contribute to their well-established social difficulties.     

Spinal Lesion Level, Shunt Status, Family Relationships, and Psychosocial Adjustment in Children and Adolescents with Spina Bifida Myelomeningocele

Investigated whether family functioning and child psychosocialadjustment were associated with spinal lesion level and shuntstatus in 65 children and adolescents with spina bifida myelomeningocele(age range = 8–16). Mothers of children with higher lesionlevels (i.e., thoracic level) reported more attachment to theirchildren, less family conflict, and a greater willingness togrant autonomy to their offspring. Such findings support a "marginality"interpretation of the data, insofar as the least physicallyimpaired children with spina bifida exhibited the greatest familydifficulties. Based on maternal report, children with shuntsperformed more poorly in school and exhibited lower levels ofcognitive competence than children without shunts. Findingsare discussed in relation to literatures on neuropsychologicalfunctioning and psychosocial adjustment in children with spinabifida.     

The Impact of BRCA1 on Spina Bifida Meningomyelocele Lesions

We examined the BRCA1 gene in 268 patients, and their parents, with a specific diagnosis of spina bifida meningomyelocele (SBMM). We genotyped two intragenic microsatellite markers ( BRCA1 D17S1323 , BRCA1 D17S1322 ) and 2 single nucleotide polymorphisms ( A1186G, A4956G ) in our patients. Transmission disequilibrium testing (TDT) showed significant association with A4956G , but not with A1186G . Extended TDT demonstrated over-transmission of the 17GT allele in BRCA1 D17S1323 and the 14GTT allele in BRCA1 D17S1322, and under-transmission of the 20GT allele in BRCA1 D17S1323 and the 16GTT allele in BRCA1 D17S1322. Our data included location of the rostral edge of the lesion. Individuals homozygous for the 17GT allele for BRCA1 D17S1323 were more likely to have SB lesions located caudally, while heterozygotes with the 17GT allele for BRCA1 D17S1323 had a more rostral lesion. Individuals heterozygous for the 16GTT allele of BRCA1 D17S1322 were more likely to have rostral lesions. We measured gene expression in CEPH members and demonstrated differential expression levels of BRCA1 associated with these polymorphisms. Integrating our data with HapMap findings showed that the polymorphic markers are associated with distinct haplotypes. We conclude that the BRCA1 gene is associated with SBMM and participates in the phenotypic variability seen in SBMM.     

Relationships among life stress, perceived family environment, and the psychological distress of spina bifida adolescents

Fifty-three teen-agers with spina bifida participated in a mail survey and completed measures of recent life events, perceived family environment, and psychological distress. Low levels of perceived family conflict and control served as life stress buffers in the prediction of distress, whereas a high level of perceived independence served as a life stress exacerbator. These interaction effects differ from those obtained for a normal sample of adolescents in the lone previous study (Burt, Cohen, & Bjorck, 1988) that reported comparable analyses. The results suggest that the process by which family environments moderate stress adjustment differs for able-bodied vs. spina bifida adolescents.     

Detection of immunoglobulin antibodies in the sera of patients using purified latex allergens

BACKGROUND: Latex allergy is largely an occupational allergy due to sensitization to natural rubber latex allergens present in a number of health care and household products. Although several purified allergens are currently available for study, information on the usefulness of these purified, native or recombinant allergens in the demonstration of specific immunoglobulin (Ig) E in the sera of patients is lacking. OBJECTIVE: To evaluate the purified latex allergens and to demonstrate specific IgE antibody in the sera of health care workers and spina bifida patients with clinical latex allergy. METHODS: Two radioallergosorbent and an enzyme-linked immunosorbent assay (ELISA) using latex proteins Hev b 1, 2, 3, 4, 6 and 7 along with two glove extracts and Malaysian nonammoniated latex (MNA) were evaluated to demonstrate IgE in the sera of health care workers and spina bifida with latex allergy and controls with no history of latex allergy. RESULTS: ELISA using the purified latex allergens demonstrated specific IgE in 32-65% health care workers and 54-100% of spina bifida patients with latex allergy. The corresponding figures for RAST were 13-48 and 23-85 for RAST-1 and 19-61 and 36-57 for RAST-2. These results were comparable with the results obtained with glove extracts and crude rubber latex proteins. CONCLUSIONS: When used simultaneously, latex proteins Hev b 2 and Hev b 7 reacted significantly with specific serum IgE in 80% of health care workers and 92% of spina bifida patients with latex allergy by ELISA technique, while this combination gave lower positivity when the RASTs were used. By the addition of Hev b 3, specific IgE was detected in all spina bifida patients with latex allergy. Both RASTs failed to show specific IgE in the control subjects, while the ELISA showed significant latex-specific IgE in 22% of controls.