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Gene & Protein in Disease

REVIEW ARTICLE
An updated review on the genetics of

arteriovenous malformations

Krisna Maddy, Anjalika Chalamgari, Ogechukwu Ariwodo, Zhuri Nisseau-Bey,
Justin Maldonado, and Brandon Lucke-Wold*
Department of Neurosurgery, University of Florida, Gainesville, Florida, USA

Abstract

Arteriovenous malformations (AVM) are congenital malformations of the cerebral
vasculature resulting in pathological shunting of blood through dilated arteries and
veins. The most common clinical manifestations of AVM are intracerebral hemorrhage,
due to rupture of these lesions as they continue to expand, which can have devastating
neurological consequences and residual deficits. The genetic underpinnings of
AVM have been explored for their role in the angiogenesis of these lesions in both
its sporadic and inherited forms. In recent times, our understanding of the genetic
variation involved in the pathogenesis AVM has advanced in both the preclinical
and clinical realms. The current review highlights in detail these advancements,
namely, the genetic underpinnings of diagnostic testing and profiling of AVM, and
the preclinical epigenetic and genetic data on AVM pathogenesis and growth. In
addition, we review the current candidate genes implicated in AVM pathogenesis in
the literature. Finally, we provide a discussion on the genetic conditions associated
with AVM and the advancements in treatment paradigms influenced by the genetic
profiles of these lesions.
*Corresponding author:
Brandon Lucke-Wold
(Brandon.Lucke-Wold@ Keywords: Arteriovenous malformations; Intracerebral hemorrhage; Genetics; Capillary
neurosurgery.ufl.edu) malformations
Citation: Maddy K, Chalamgari A,
Ariwodo O, et al., 2023, An
updated review on the genetics of
arteriovenous malformations. Gene 1. Introduction
Protein Dis, 2(2): 0312.
https://doi.org/10.36922/gpd.0312 Arteriovenous malformations of the brain (bAVM) have long presented a unique challenge
Received: March 3, 2023 to clinicians. An arteriovenous malformation (AVM) is typically defined as an unusual
Accepted: June 7, 2023 or abnormal shunt bypassing the capillary bed and connecting an artery and a vein .
[1]
Published Online: June 26, 2023
Depending on their location and development, rupture of these congenital vasculature
Copyright: © 2023 Author(s). connections can result in many complications, including abscess, hypoxia, and even
This is an Open Access article
distributed under the terms of the intracranial hemorrhage (ICH) (Figure 1). Most treatment is aimed at surgically correcting
Creative Commons Attribution the bAVM, often through various means involving embolization, resection, or, more
License, permitting distribution, recently, controlled doses of radiation [2,3] . Although these interventions prove effective,
and reproduction in any medium,
provided the original work is with the most notable being recanalization, complications can persist, more frequently
properly cited. in cerebral AVM [4,5] . Surgical intervention may also simply be less beneficial in a patient
Publisher’s Note: AccScience with multiple bAVM or a smaller, less focal malformation. For these and other individuals,
Publishing remains neutral with medical management is key, yet there remains a dearth of medical therapies available for
regard to jurisdictional claims in [6] [7]
published maps and institutional bAVM . This is due to ambiguity surrounding its pathophysiology . While much has been
affiliations. suggested in terms of the etiology of the anomaly, no causative factor has been identified.

Volume 2 Issue 2 (2023) 1 https://doi.org/10.36922/gpd.0312