Genetic Insights into Cerebrovascular Disorders: a Comprehensive Review

Abstract

Genetic vascular disorders are usually present at birth;
structurally, they tend to grow proportionately with the
child, and do not regress spontaneously. The malformations vary greatly in number, size, and location, and can
also occur in the context of syndromes. Cerebrovascular
malformations are defined as localized structural defects
of the vasculature, named after the type of vessel affected [1]. Although the majority of vascular malformations
are sporadic, a small proportion may be inherited.
Due to the relative rarity of cerebrovascular malformations and the broad spectrum of possible complications,
much of the evidence for genetic etiology comes from
single studies conducted in small and homogenous populations.
With the advances of molecular technologies and medical research, genetic testing for a more proactive and
precise clinical management is becoming a cornerstone
in the diagnostic workup for patients, especially for neurological diseases.
The prevalence of intracranial vascular malformation
has been shown to be increasing over time. This is
believed to be due to the advancement in radiological
procedures. Many studies examining neurological syndromes have aimed at early identification of intracranial
malformations, to prevent possible complications. With
the advancement of medical genetics, represented by the
recent breakthrough of whole exome sequencing, the
proportion of neurological disorders that can be attributed to identifiable genetic mutations is increasing.
Vascular malformations are believed to result from a
somatic mutation creating a mosaic clinical phenotype,
in which two genetically distinct populations of cells
exist within the same individual [2]. In this review, we
reviewed published English language medical literature,
describing genes related to the development of intracranial vascular disorders, with their perspective malformations. Since these genes play vital roles in the embryonic
process of vasculogenesis, as well as the post-embryonic
processes of angiogenesis and arteriogenesis, it is very difficult to assign genes to a specific anatomical or histological category. Therefore, we classified the genetic
information in relation to the underlying histopathological manifestations.
To simplify the classification process, and to make it
more attributable to clinical practice, we categorized the
intracranial malformations based on their pathology,
which can be histologically differentiated from one
another based on the underlying molecular genetics.