Genetics of Central Nervous System Arteriovenous Malformations (GENE-MAV) (GENE-MAV)

Genetics of Central Nervous System Arteriovenous Malformations (AVM): Genotype-Phenotype Correlation and Prognostic Impact on Patients With AVM

Cerebral and medullary arteriovenous malformations (AVMs) lead to arterial and venous networks to communicate pathologically, creating an arteriovenous shunt. The occurrence of intracranial haemorrhage is the most important prognostic factor of AVMs because it is associated with a significant morbidity and mortality. The genetic, molecular and cellular mechanisms that cause vascular malformations of the central nervous system are partially known and the influence of genetic damage on the prognosis of AVMs is poorly known.

Study Overview

• Status: Recruiting
• Conditions: Arteriovenous Malformations
• Intervention / Treatment: Genetic: blood sample

Detailed Description

Cerebral and medullary arteriovenous malformations (AVMs) are morphologically abnormal vessels located on the surface or in the cerebral or medullary parenchyma. These vascular lesions cause the arterial and venous networks to communicate pathologically, creating an arteriovenous shunt.

The prevalence of cerebral Cerebral and medullary AVMs in general population is difficult to establish given the rarity of the condition. However, it is estimated at around 1 per 10,000 inhabitants (0.01%). About 15-20% of the cerebral vascular accidents are asymptomatic at the time of diagnosis. The occurrence of intracranial haemorrhage is the most important prognostic factor because it is associated with a significant morbidity and mortality. The management of an AVM is usually carried out in a multidisciplinary way, combining interventional neuroradiology, neurosurgery and vascular neurology.

The genetic, molecular and cellular mechanisms that cause vascular malformations of the central nervous system are partially known. Several recent research works highlight mutations in the RAS-MAPK or MAPK-ERK signalling pathway in AVMs. In cases of cerebral AVMs considered to be sporadic, a somatic KRAS/BRAF mutation has recently been demonstrated in tissue samples of operated AVMs.

Except in the case of Hereditary Haemorrhagic Telangiectasia (HHT or Rendu-Osler-Weber syndrome), the influence of genetic damage on the prognosis of AVM is poorly known. It is also interesting to note that genetic screening is not routinely performed in patients with cerebro-medullary AVMs and that therefore the prevalence of these clinical entities in patients with AVMs is not known.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Stanislas Smajda, MD; Phone Number: 0148036454; Email: ssmajda@for.paris
• Study Contact Backup: Name: Amélie Yavchitz, MD; Phone Number: 0148036454; Email: ayavchitz@for.paris

Study Locations

• France
  • Paris, France, 75019
    • Recruiting
    • Hôpital Fondation Adolphe de Rothschild
    • Contact: Stanislas SMAJDA, DR; Email: ssmajda@for.paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The recruited population will be index cases with cerebrovascular cerebral vascular malformations treated in the participating centres

Description

Inclusion Criteria:

• Patient with a vascular malformation of the cerebral or medullary identified on diagnostic imaging (angio-CT, angio-MRI or diagnostic angiography) for which clinical monitoring alone or intervention (endovascular treatment, surgery or radiosurgery) is planned in the centres participating in the research.

Exclusion Criteria:

• Pregnant, parturient or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic mutation	Presence of a pathogenic mutation in one of the genes tested in the panel or identification of a pathogenic mutation following sequencing of the exome and/or transcriptome of the patient and/or his/her parents.	limit of 12 month

Collaborators and Investigators

• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild
• Investigators: Principal Investigator: Stanislas Smajda, MD, Fondation Ophtalmologique Adolphe de Rothschild

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Vascular Malformations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Arteriovenous Malformations; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: SSA_2021_3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No