Genetic Research Unravels Causes of Rare and Complex Vascular Disorder

Recent genetic studies have shed light on the underlying mechanisms of a rare vascular disorder known as arteriovenous malformation (AVM), which can be life-threatening. These abnormal tangles of blood vessels can occur anywhere in the body, with extracranial AVMs being particularly invasive and difficult to treat, often requiring surgical intervention and prone to recurrence.

A groundbreaking study conducted by researchers at The University of Osaka analyzed tissue samples from 30 patients—representing the largest collection of extracranial AVM cases subjected to genetic analysis to date. The team aimed to identify genetic mutations associated with the disease and understand its pathology more precisely.

The findings revealed that nearly half of the patients carried mutations in the RAS/RAF/MAPK signaling pathway, a critical pathway that regulates cell growth and communication. These mutations were especially prevalent in younger female patients and were linked to the characteristic abnormal blood vessel formation.

Further analysis showed increased activity of certain genes within the AVMs, notably the gene MAP4K4, which is involved in cell movement and blood vessel growth. Elevated activity of this gene appears to contribute to the development of AVMs by promoting abnormal angiogenesis. Additionally, the downstream effector ERK was found to be hyperactive across all cases, including those without detectable mutations, signaling the pathway's central role.

These insights open new avenues for targeted therapies, as clinical trials involving inhibitors of the RAS/RAF/MAPK pathway are already underway internationally. Such precision medicine approaches could potentially offer effective treatment options with fewer invasive procedures and a lower risk of recurrence.

This study marks a significant step forward in understanding AVMs and highlights the promise of genetic analysis in developing tailored therapies for complex vascular disorders.

Source: https://medicalxpress.com/news/2025-07-genetics-untangle-rare-complex-vascular.html