The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Abstract

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.

Keywords: children; diagnostics; genetics; stroke; treatment.

Figure 1

Schematic presentation of pediatric stroke causes. AIS, arterial ischemic stroke; CSVT, cerebral sinovenous thrombosis; CVT, cortical vein thrombosis; SAH, subarachnoid hemorrhage; ICH, intracerebral hemorrhage.