COL4A1 brain small-vessel disease

Last revised by Rohit Sharma on 21 Jan 2023

COL4A1 brain small-vessel disease is an autosomal dominant monogenic COL4A1-related disorder that primarily causes cerebral small vessel disease.

The exact prevalence is unknown, but the condition is likely under-diagnosed.

The clinical presentation is varied but generally presents during adulthood (30-50 years of age) with CNS features, including 1-4:

Notably, dementia is not a feature of COL4A1 brain small-vessel disease 1. Furthermore, multi-organ involvement (including features of other COL4A1-related disorders) has also been rarely reported in patients with COL4A1 brain small-vessel disease, including cataracts, retinal hemorrhages, Axenfeld-Rieger anomaly, nephropathy, muscle cramps, mitral valve prolapse, arrhythmias, and Raynaud phenomenon 1-4.

COL4A1 brain small-vessel disease is an autosomal dominant condition resulting from a mutation to the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen 1-6. Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels 1-6.

A similar syndrome is seen in patients with mutation to the COL4A2 gene 3

Histological analysis of affected blood vessels reveals interruption and thickening of basement membrane 1.

CT is non-specific, demonstrating white matter regions of low attenuation 1-4.

MRI is the investigation of choice and demonstrates the following features:

Angiographic studies may demonstrate the presence of intracranial cerebral aneurysms, most commonly affecting the intracranial internal carotid artery or middle cerebral artery 1-4.

No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 2.

General imaging differential considerations include:

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