The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact

Abstract

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.), highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans.

Molecular Signatures of Normal Pressure Hydrocephalus: A Large-scale Proteomic Analysis of Cerebrospinal Fluid

“…Moreover, our study identifies the downregulation of specific genes, such as L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1, which have been previously well characterized as playing an important role in congenital hydrocephalus and aqueductal stenosis [57][58][59][60][61][62][63][64] . The downregulation of L1CAM, a gene extensively studied and phenotyped for its role in X-linked congenital hydrocephalus, is particularly noteworthy 57,61 .…”