1/23. Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region.Studies in mouse, chicken and xenopus have shown that Slug is selectively expressed in the dorsal part of the developing neural tube. Ablation and antisense experiments in chicken suggest that Slug may be an important factor during neural tube closure. We therefore investigated the role of Slug as a possible candidate contributing to the aetiology of neural tube defects (NTD) in humans. We characterised the genomic structure of human SLUG including determination of the exon-intron boundaries. The coding sequence of SLUG was screened for mutations in 150 patients with NTD using single strand conformation analysis (SSCA). In one patient, we identified a missense mutation 1548C-->A in exon 2 causing an exchange of a conserved amino acid (D119E) in the Slug subfamily-defining region preceding the first zinc finger. This is the first description of a human mutation in the SLUG gene. In accordance with the findings in model organisms, the SLUG mutation may be causally related to the development of NTD in our patient and could be considered as a predisposing factor.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
2/23. Rudimentary meningocele: remnant of a neural tube defect?BACKGROUND: Rudimentary meningocele, a malformation in which meningothelial elements are present in the skin and subcutaneous tissue, has been described in the past under a variety of different terms and has also been referred to as cutaneous meningioma. There has been debate as to whether rudimentary meningocele is an atretic form of meningocele or results from growth of meningeal cells displaced along cutaneous nerves OBJECTIVE: We reviewed the clinical, histological, and immunohistochemical characteristics of rudimentary meningocele in an attempt to assess the most likely pathologic mechanism for it. DESIGN: Retrospective study. SETTING: University hospitals. patients: Thirteen children with rudimentary meningocele. MAIN OUTCOME MEASURES: medical records were reviewed and histopathologic examination as well as immunohistochemistry studies were performed for each case. A panel of immunoperoxidase reagents (EMA, CD31, CD34, CD57, S-100, and CAM 5.2) was used to assess lineage and to confirm the meningothelial nature of these lesions. RESULTS: Recent evidence indicating a multisite closure of the neural tube in humans suggests that classic meningocele and rudimentary meningocele are on a continuous spectrum. CONCLUSION: Rudimentary meningocele seems to be a remnant of a neural tube defect in which abnormal attachment of the developing neural tube to skin (comparable to that in classic meningocele) could explain the presence of ectopic meningeal tissue. In the majority of cases, no underlying bony defect or communication to the meninges could be detected. However, in light of the probable pathogenesis, imaging studies to exclude any communication to the central nervous system should precede any invasive evaluation or intervention.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
3/23. Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality.Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.- - - - - - - - - - ranking = 0.010780945248223keywords = drug (Clic here for more details about this article) |
4/23. Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with down syndrome and neural tube defect.The association of neural tube defects (NTDs) with down syndrome (trisomy 21) and altered folate metabolism in both mother and affected offspring provide a unique opportunity for insight into the etiologic role of folate deficiency in these congenital anomalies. We describe here the case of a male child with trisomy 21, cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed homozygosity for the mutant 677C-->T polymorphism in both the mother and child. The plasma homocysteine of the mother was highly elevated at 25.0 micromol/L and was associated with a low methionine level of 22.1 micromol/L. Her s-adenosylhomocysteine (SAH) level was three times that of reference normal women, resulting in a markedly reduced ratio of s-adenosylmethionine (SAM) to SAH and significant dna hypomethylation in lymphocytes. The child had low plasma levels of both homocysteine and methionine and a reduced SAM/SAH ratio that was also associated with lymphocyte dna hypomethylation. In addition, the child had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. We suggest that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21. Altered folate status and homozygous TT mutation in the MTHFR gene in both mother and child would be expected to increase the risk of neural tube defects. The presence of both trisomy 21 and postclosure NTD in the same child supports the need for an extended periconceptional period of maternal folate supplementation to achieve greater preventive effects for both NTD and trisomy 21.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
5/23. Embryonic hydromyelia: cystic dilatation of the lumbosacral neural tube in human embryos.In a large collection of human embryos (the Kyoto Collection of Human Embryos, Kyoto University), we encountered five cases with abnormal dilatation of the neural tube at the lumbosacral level. In these examples, the central canal was enlarged, and the roof plate of the neural tube was extremely thin and expanded. The mesenchymal tissue was scarce or lacking between the roof plate and the surface ectoderm. This type of anomaly was assumed to be formed after neural tube closure and may be an early form of spina bifida. In two of the cases, some abnormal cells were found ectopically between the thin roof plate and the surface ectoderm. Morphologically, these cells resembled those forming spinal ganglia and could be of the neural crest origin. Since neural crest cells are pluripotent and can differentiate into a variety of tissues, such ectopic cells might undergo abnormal differentiation into teratomatous tumors and/or lipomas, which are frequently associated with spina bifida. We also discuss the definition of spina bifida and the classification of neural tube defects from the embryological and pathogenic viewpoints and propose a new classification of neural tube defects.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
6/23. muscle weakness and paresthesia associated with epidural analgesia in a patient with an intrathecal neurofibrolipoma as part of a tethered cord syndrome.We report a case of a 75-yr-old female patient in whom motor deficits and paresthesias occurred after lumbar epidural analgesia. These symptoms were eventually found to be due to a tethered cord syndrome. An epidural catheter was inserted for analgesia after colon surgery. The postoperative course was characterized by fluctuating sensory and motor symptoms. A magnetic resonance imaging scan showed an intraspinal mass, which was removed by laminectomy. The presented complication is of major interest because the intraspinal tumor, which must have been present for years, became acutely symptomatic. Tethered cord syndrome is caused by a limited longitudinal mobility of the cord. It is often seen as a part of spinal closure defects and is also associated with intrathecal tumors. Typically, adult patients complain of weak legs, paresthesias of the legs, and urinary incontinence. However, our patient had denied any muscular or neurological problems or urinary incontinence during the preoperative interview. Postoperative electromyogram and electroneurography ascertained chronic neurogenic lesions of multiple lumbar and sacral nerve roots. Three months after the operation, the patient was able to walk 100 m with a crutch.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
7/23. Diastematomyelia: a case with familial aggregation of neural tube defects.Intrauterine neural tube defects, meningomyelocele, and diastematomyelia are developmental errors at different stages of the closure of the neural tube. The familial aggregation of these neural tube defects is not previously reported in the literature and should make one think about a common embryogenesis and a possible common mechanism of etiopathogenesis leading to anomalies at different stages of this embryogenesis. This paper presents a 12-year-old Turkish boy with diastematomyelia who was suspected with a demonstrative dermatologic finding without any neurologic sign and diagnosed with magnetic resonance imaging (MRI). He has a positive family history of a stillbirth with neural tube defect, an exitus with meningomyelocele, and an epileptic child in his female siblings.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
8/23. Triple neural tube defect--cranium bifidum with rostral and caudal spina bifida--live evidence of multi-site closure of the neural tube in humans.OBJECTIVE: The coexistence of three neural tube defects (NTDs) in a single child is an exceptional event. A review of the literature revealed nine published "double" NTD cases, but no cases of "triple" NTDs have been reported to date. CASE REPORT: The rare case of a two-year-old boy with three distinct NTDs is presented. The boy had a 17x15x15-cm(3) parieto-occipital encephalocele, a small cervical myelomeningocele, and a 11x11x8-cm(3) thoracolumbar myelomeningocele. hydrocephalus and Chiari II malformation accompanied the NTDs. All three lesions were surgically treated with good cosmetic results and satisfactory neurologic outcome. CONCLUSIONS: Current neural tube closure theories and models are reviewed in an attempt to better understand this extremely unusual coexistence. The multi-site closure model is clearly more useful in our understanding of NTDs.- - - - - - - - - - ranking = 6keywords = closure (Clic here for more details about this article) |
9/23. Intradural mesh: an unusual cause of spinal cord tethering: case report.A 13-year-old boy with a myelomeningocele experienced progressive foot deformity and lower-extremity pain while walking. magnetic resonance imaging demonstrated a low-lying spinal cord with scarring near the site of a previous repair. During surgery, the terminal nerve roots were found to have scarred and adhered to a piece of metal mesh lying in the intradural space. The mesh had originally been placed to bridge a sacral ossification defect that was present at the initial closure of the child's myelomeningocele.- - - - - - - - - - ranking = 1keywords = closure (Clic here for more details about this article) |
10/23. Antiepileptic drugs: a case report in a pregnancy with a neural tube defect.While receiving lamotrigine, a patient pregnant with triplets suffered a double fetal neural tube defect. plasma homocysteine, folate, vitamins B12 and B6 (pyridoxal phosphate), and red cell folate levels were measured in samples while she was receiving folic acid therapy for 1 month during the second trimester of pregnancy. Some mutations were sought, involved in homocysteine metabolism and linked with the folate metabolism. Her results were compared with those of a pregnant woman with normal triplets and with those of 58 pregnant women, with a normal pregnancy. Results indicated a decrease in vitamin B12 and B6 values in plasma in the patient, and a genotype AG (polymorphism A66G) was observed, but was not found in the pregnant woman with normal triplets. Even if lamotrigine therapy is not known to be associated with significant changes in red cells or in serum folate, periconceptional folic acid supplementation is counseled for women, along with periconceptional B12 and B6 vitamin supplementation when their plasma values are decreased.- - - - - - - - - - ranking = 0.043123780992892keywords = drug (Clic here for more details about this article) |
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