Related Experiment Video
Updated: Jul 10, 2026
Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
Clinical and brain MRI follow-up study of a family with COL4A1 mutation
K Vahedi1, M Boukobza, P Massin
1Service de Neurologie, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Neurologie, 2 rue Ambroise Paré, 75010 Paris, France. katayoun.vahedi@lrb.aphp.fr
Insights
COL4A1 mutations cause diverse small vessel disease, with some family members remaining asymptomatic and showing no MRI progression over time. This highlights varied clinical expression in genetic small vessel disease.
Area of Science:
- Genetics
- Neurology
- Vascular Biology
Background:
- Collagen Type IV Alpha 1 Chain (COL4A1) mutations are a newly identified genetic cause of small vessel disease affecting the brain and retina.
- Understanding the clinical spectrum and natural history of COL4A1 mutations is crucial for diagnosis and management.
Observation:
- A 7-year follow-up study of a family with a COL4A1 mutation was conducted.
- Clinical data and brain MRI scans were collected for affected members.
- Two individuals died from intracranial hemorrhage during the study period.
Findings:
- Four mutation carriers (ages 25-74) showed diverse clinical presentations.
- No stroke, retinal hemorrhage, or hematuria was reported; dementia was absent per DSM-IV criteria.
- Brain MRI revealed diffuse leukoencephalopathy (grade 3), dilated perivascular spaces, and silent microbleeds in most patients.
- Vascular changes on MRI remained stable over the follow-up period.
Implications:
- COL4A1 mutation carriers exhibit significant variability in disease expression within families.
- Asymptomatic carriers with stable vascular changes on brain MRI are possible.
- This variability necessitates personalized approaches to managing COL4A1-related small vessel disease.
Objective:
To better delineate the clinical spectrum and the natural history of COL4A1 mutations, a newly defined genetic cause of small vessel disease including the brain and retina.
Methods:
Clinical and brain MRI follow-up study of a family with COL4A1 mutation.
Results:
During a 7-year period, two affected members died from intracranial hemorrhage. Four other members had a COL4A1 mutation (age ranges 25 to 74 years). None reported stroke or retinal hemorrhage or hematuria and none had dementia according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Follow-up brain MRI showed grade 3 diffuse leukoencephalopathy in three out of four patients. All had dilated perivascular spaces and three out of four had silent microbleeds mainly in the deep white matter. MRI signal abnormalities did not change in severity, number, or location between baseline and follow-up imaging.
Conclusions:
COL4A1 mutation carriers have great diversity in the clinical expression of the disease within the same family. Some affected family members may remain asymptomatic during several years of follow-up and have no evidence of progression of vascular changes on brain MRI.
More Related Videos
Related Concept Videos
01:21Aneurysm II: Clinical Manifestations and Diagnostic Studies
01:21Imaging Studies for Cardiovascular System IV: CMRI
01:27Imaging Studies IV: Magnetic Resonance Imaging