Genetic Aspects of Pathogenesis of Congenital Spastic Cerebral Paralysis

Abstract

Congenital spastic cerebral palsy (СР) is a large group of non-progressive disorders of the nervous system. The basis of the pathogenesis of these conditions is considered the impact of many factors. The clinical diversity of the disease and the syndromic principle of classification determine the existing uncertainties in the diagnosis of these diseases. The multifactorial nature of the underlying brain lesions is obvious and beyond doubt. The volume of information accumulated to date does not allow one to exclude the role and significance of the direct effect of acute asphyxiation in childbirth on a fetus normally formed during pregnancy, the role of infectious brain lesions, and disorders of neuronal migration. It is impossible to ignore the dependence of the clinical picture of the disease on what stage of ontogenesis the impact of the damaging agent occurs. As one of the pathogenetic factors, the genetic determinism of the phenotype of the clinical picture of a disease is fairly considered. This review focuses on the genetic aspects of the pathogenesis of this pathology. The information on monogenic mechanisms of inheritance is analyzed in detail. Such genetically determined mechanisms of pathogenesis as the inheritance of prerequisites for brain trauma in the perinatal period are considered separately. The new clinically significant variants of chromosomal mutations found in patients with CР are reviewed in detail, the evidence of the influence of genetic factors on the development of cerebral palsy in the absence of a pronounced monogenic cause of the disease, obtained through twin studies, is reviewed. Lit search of polymorphisms markers of predisposition to the development of cerebral palsy genes of the folate cycle, genes of glutamate receptors, the gene of apolipoprotein and of the gene for the transcription factor of oligodendrocytes (OLIG2) in Detail the role of epigenetic effects on the activity of genes coding for mitochondrial proteins.

Keywords

• cerebral palsy
• pathogenesis
• candidate genes
• sequencing