COL4A1 brain small-vessel disease

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

Epidemiology

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

Clinical presentation

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

Notably, dementia is not a feature of COL4A1 brain small-vessel disease . 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 .

Pathology

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 . Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels .

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

Histology

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

Radiographic features

CT

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

MRI

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

CTA / MRA

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

Treatment and prognosis

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

Differential diagnosis

General imaging differential considerations include: