Dataset Information

Molecular Biology of Pediatric Hydrocephalus and Hydrocephalus-related Diseases.

ABSTRACT: We are beginning to understand the molecular biology of hydrocephalus and its related diseases. X-linked hydrocephalus (XLH), holoprosencephaly (HPE), Dandy-Walker malformation (DWM), and neural tube defect (NTD) can all be discussed with respect to their available molecular genetics knowledge base and its clinical applications. XLH is single gene disorder caused by mutations in the neural cell adhesion molecule-encoding L1CAM (L1) gene. Our knowledge of the molecular basis of XLH is already being applied clinically in disease diagnosis, disease classification, and prenatal diagnosis. However, the molecular mechanism underlying XLH-related hydrocephalus still needs to be clarified. Sixteen causative genes for HPE have been identified, of which mutations are most often found in SHH, ZIC2, SIX3, and TGIF. Genetic interactions, gene complexity, and the wide variety of HPE phenotypes and genotypes are topics for future study. For DWM, two important loci, 3q24, which includes the FOXC1 gene, and 6q25.3, which includes the ZIC1 and ZIC4 genes, were recently identified as causative areas. The planar cell polarity (PCP) genes CELSR1, CELSR2, VANGL1, and VANGL2 have been implicated in NTD; these genes have roles in neural tube closure and ependymal ciliary movement.

SUBMITTER: Yamasaki M

PROVIDER: S-EPMC4628154 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Molecular Biology of Pediatric Hydrocephalus and Hydrocephalus-related Diseases.

Yamasaki Mami M Kanemura Yonehiro Y

Neurologia medico-chirurgica 20150731 8

We are beginning to understand the molecular biology of hydrocephalus and its related diseases. X-linked hydrocephalus (XLH), holoprosencephaly (HPE), Dandy-Walker malformation (DWM), and neural tube defect (NTD) can all be discussed with respect to their available molecular genetics knowledge base and its clinical applications. XLH is single gene disorder caused by mutations in the neural cell adhesion molecule-encoding L1CAM (L1) gene. Our knowledge of the molecular basis of XLH is already bei ...[more]

PMID: 26227058

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Project description:BackgroundPediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.MethodsTo date, four hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus before adulthood. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. Data such as hydrocephalus etiology and details of shunt revision history. All data are entered under a coded identifier.Results293 shunt samples were collected from 228 pediatric patients starting from May 2015 to September 2019. We saw a significant difference in the number of revisions per patient between centers (Kruskal-Wallis H test, p value < 0.001). The leading etiology at all centers was post-hemorrhagic hydrocephalus, a fisher's exact test showed there to be statistically significant differences in etiology between center (p = 0.01). Regression showed age (p < 0.01), race (p = 0.038) and hospital-center (p < 0.001) to explain significant variance in the number of revisions. Our model accounted for 31.9% of the variance in revisions. Generalized linear modeling showed hydrocephalus etiology (p < 0.001), age (p < 0.001), weight and physician (p < 0.001) to impact the number of ventricular obstructions.ConclusionThe retrospective analysis identified that differences exist between currently enrolled centers, although further work is needed before clinically actionable recommendations can be made. Moreover, the variables collected from this chart review explain a meaningful amount of variance in the number of revision surgeries. Future work will expand on the contribution of different site-specific and patient-specific factors to identify potential cause and effect relationships.

Dataset Information

Molecular Biology of Pediatric Hydrocephalus and Hydrocephalus-related Diseases.

Publications

Molecular Biology of Pediatric Hydrocephalus and Hydrocephalus-related Diseases.

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