Relationship between NOTCH4 gene polymorphism and brain arteriovenous malformation development: a systematic review

Background: Brain arteriovenous malformations (BAVM) are a cause of intracranial hemorrhage (ICH). The basic morphology of BAVM consists of a tangle of abnormal and dilated channels with intervening gliosis, that directly shunts blood circulation between the arteries and veins without a true capillary bed. Some gene polymorphisms have been shown to play an important role in the prediction of the BAVM, in this case, the NOTCH4 gene polymorphism.

Objectives: The aim of this study was to review systematically and critically previous studies of the clinical prevalence of NOTCH4 gene polymorphism as a risk fator for the Brain Arteriovenous Malformations development.

Methods: A systematic literature search was performed using PubMed and Scielo. Selected articles had to describe a study that provided a prevalence and/or incidence number for the population with NOTCH4 gene polymorphism and brain arteriovenous malformation.

Results: A total of 85 articles were found, but only thirteen studies reporting the relationship between the NOTCH4 polymorpohism and brain arteriovenous malformations met the inclusion criteria. In most of them (approximately 50%), the authors suggest NOTCH4 polymorphism and the NOTCH signaling pathway as a factor involved in the brain arteriovenous malformations development.

Conclusions: Although the literature on the prevalence and incidence of NOTCH4 gene polymorphism is limited, there is a general consensus that this kind of polymorphism can be considered as possible genetic risk fator in brain arteriovenous malformation development. In addition, large studies are still needed that can prove the relationship between NOTCH4 and BAVM, so that therapeutics can be created to prevent clinical manifestations of this kind of disease.