Background Even today, myelomeningocele (MMC) is still encountered in clinical medicine and its incidence has not decreased over the last 20 years despite a known reduction in risk due to the use of folic acid supplements. The spectrum of clinical symptoms is extremely broad and, depending on the level of the defect, varies from mild to severe. Subject to the degree of paralysis, patients are reliant on the use of orthopaedic aids and orthoses for the treatment of primary contractures and deformities and the prevention of secondary ones. This forms the basis for attaining or maintaining mobility in many patients. The objective of the study was to determine the practical application of the proposed Ferrari concept for the provision of orthoses for children and adults. Patients and Material The retrospective study comprised medical records of 180 patients (97m) with an average age of 19.44 years (3-52 years, SD 9.3) at the time of investigation. The average duration of treatment was 15.34 years (138 years, SD 8.96). Data relating to deformities of the vertebral column and lower limbs, provision of hydrocephalus shunts and orthoses, and patient mobility was evaluated. Results Most patients were given systematic treatment with orthoses at an early stage. In 58,9% of cases, it was possible to implement the proposed concept for providing patients with dynamic orthoses, whereby the treatment concept was more difficult to implement with high lumbar lesions than with lower lesions. Moreover, a decrease in the patients' mobility with increasing age was noticeable. Some 42.3% of adult patients were able to walk with marked variations in mobility in relation to the different levels of lesions. Conclusion Taking into consideration the complexity of both the clinical picture and therefore the provision of orthopaedic devices, the result of the implementation of the proposed orthotic concept can be considered positive. Similarly, early commencement of provision of orthoses and hence the possibility of achieving a positive influence on later mobility can be considered a success. The need for individual concepts and further development in order to increase mobility particularly in the case of patients with thoracic or high lumbar lesions is evident. A more comprehensive provision of information to patients regarding orthotic treatment options and their consequences for prophylaxis and quality of life should be an important component of interdisciplinary long- term patient care.

Neural tube defects (NTD) are among the most common congenital malformations in humans. The current view is that there are no major genes causing NTDs, but combinations of sequence variants in different genes have additive effects on determining the malformation. Therefore it is important to identify such sequence variants to get a better understanding of NTD pathogenesis. Studies on animal models have shown that BMP4 and NOG are involved in the patterning of the neural tube. We therefore performed a single-strand conformation analysis (SSCA) mutation screen for both genes in 179 spina bifida aperta (SBA) patients. Our SSCA screen revealed four missense mutations in BMP4 and one in NOG. It is likely that these mutations have acted together with other gene variants in independently segregating loci as susceptibility factors in these SBA cases. In addition, a case-control association study provides evidence for a genotype disequilibrium of BMP4 polymorphism 455T-->C (V152A) in exon 5. The frequency of the heterozygous 455TC genotype is lower in cases than in controls (nominal P=0.017), although allele frequencies are similar in both groups. A possible explanation for this finding might be that BMP4 455TC heterozygosity at this site is a protective factor in the normal population, although this hypothesis cannot be proven to date.

BACKGROUND:Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing neural tube.METHODS:A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRalpha, and PAX1 already shown to be related to NTD.RESULTS:Two TFAP2alpha point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57-5.39).CONCLUSIONS:Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases.

From 1979 to 1983, EMG and/or muscle biopsy studies were done in twenty-one of twenty-two patients seen in our institution for the first time for arthrogryposis multiplex congenita (AMC). Most of the muscle biopsies were done with a needle. As expected, the final diagnosis in these patients was very heterogeneous since it is well recognized that AMC can be due to any factor that interferes with fetal mobility. We found however a surprisingly high number of patients (9/22) affected by a myopathic disease. Based on these results, we feel that needle muscle biopsy should be included as a routine procedure in infants affected by AMC since by clarifying the diagnosis it helps in improving genetic counselling and prognosis in these patients. It is now widely accepted that arthrogryposis multiplex congenita (AMC) is not in itself a disease but is secondary to any factor that interferes with fetal movements. The joint deformities seen in these children can be due to mechanical factors (oligohydramnios for example), central or peripheral nervous system disorders, muscle diseases... (Dubowitz 1978, Hageman and Willemse 1983, Hall 1981, Swinyard 1982). However, the relative frequency of each etiologic factor remains unclear since in spite of the abundant literature on the subject, we found only three reports describing the findings of electromyographic (EMG) and muscle biopsy studies done systematically in unselected groups of children affected by AMC (Amick et al 1967, Bharucha et al 1972, Dastur et al 1972, Kullmann and Szijj 1973). Furthermore, each article reached different conclusions in regard to the occurrence of these various etiologies in their respective patients.(ABSTRACT TRUNCATED AT 250 WORDS)