RESUMO
Background: With an incidence of 2-4% in all newborns, developmental dysplasia of the hip, DDH, represents the most frequent congenital disorder of the skeletal system in Germany. The therapy options are deduced with the help of a sonography. The conservative therapy approach includes the application of flexion abduction orthoses, which lead to a development of the child's hip through abduction and flexion angle. The overall structure of the orthoses puts a strain on the axial skeleton of the children. The following work is intended to clarify what role the design of the orthoses plays in this respect. Methods: Inclusion criterion for the study was fully developed newborns without an indication of skeletal malformations with Type I hip joints according to Graf verified by ultrasound. A total of 19 newborns were recruited and included in the period 3/2013-01/2015. Two types of orthoses used in treating developmental dysplasia of the hip (Tübinger splint, Otto Bock; hip flexion abduction orthosis (Superior orthosis) according to Mittelmeier-Graf, AIDAMED e.K (Kreuz et al., 2012; Mittelmeier et al., 1998; Schmitz et al., 1999), constructions differ, were used. Force was measured with the help of three force sensors, which were even able to be integrated into these without changing the design of the orthosis. In this closed system, force transmission was measured for the duration of a fixed period of two minutes. Findings: The greatest axial force development (overall force) is in the Tübinger splint with an average force of 15.1 N (min. 0.59 N, max. 53.09 N, mean 15.1, SD 2.46). 4.09 N (min. 0.96 N, max. 20.99 N, mean 4.09, SD 0.65) resulted in the Superior orthosis. Significant correlations between body weight and resulting axial traction - on average during the entire measurement period and in movement - can be taken from the statistical analysis regarding the Tübinger splint. Such a correlation cannot be depicted for the Superior orthosis. Interpretation: The analysis of the load transmission of the examined flexion and abduction orthoses reveals differences between the models. The construct of the orthoses in itself appears to play a significant role. Long-term effects of orthosis therapy on a child's axial skeleton have not been studied to date. Furthermore, it seems reasonable to expand the test series to orthoses, the design of which is configured in a similar matter compared to the examined aids. Conclusion: This study proves that the orthotic design has an influence on the infant's axial load.
RESUMO
Cerebral cavernous malformations (CCM) are vascular lesions of the central nervous system that can cause headaches, seizures and hemorrhagic stroke. Disease-associated mutations have been identified in three genes: CCM1/KRIT1, CCM2 and CCM3/PDCD10. The precise proportion of deep-intronic variants in these genes and their clinical relevance is yet unknown. Here, a long-range PCR (LR-PCR) approach for target enrichment of the entire genomic regions of the three genes was combined with next generation sequencing (NGS) to screen for coding and non-coding variants. NGS detected all six CCM1/KRIT1, two CCM2 and four CCM3/PDCD10 mutations that had previously been identified by Sanger sequencing. Two of the pathogenic variants presented here are novel. Additionally, 20 stringently selected CCM index cases that had remained mutation-negative after conventional sequencing and exclusion of copy number variations were screened for deep-intronic mutations. The combination of bioinformatics filtering and transcript analyses did not reveal any deep-intronic splice mutations in these cases. Our results demonstrate that target enrichment by LR-PCR combined with NGS can be used for a comprehensive analysis of the entire genomic regions of the CCM genes in a research context. However, its clinical utility is limited as deep-intronic splice mutations in CCM1/KRIT1, CCM2 and CCM3/PDCD10 seem to be rather rare.