COL4A1 brain small-vessel disease is an autosomal dominant monogenic COL4A1-related disorder that primarily causes cerebral small vessel disease.
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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 1-4:
hemorrhagic stroke: generally subcortical in location, involving the centrum semiovale, deep grey matter, or brainstem
ischemic stroke: generally lacunar infarcts
migraine with aura
seizures
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.
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 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.
Microscopic appearance
Histological analysis of affected blood vessels reveals interruption and thickening of basement membrane 1.
Radiographic features
CT
CT is non-specific, demonstrating white matter regions of low attenuation 1-4.
MRI
MRI is the investigation of choice and demonstrates the following features:
widespread confluent, bilateral, symmetric white matter hyperintensities on T2-weighted sequences, with relative sparing of subcortical U-fibers 1-4
dilated perivascular spaces 1-4
cerebral microhemorrhages, predominantly involving the centrum semiovale, deep grey matter, or brainstem 1-4
intracerebral hemorrhage in the same distribution as cerebral microhemorrhages 1-4
ischemic stroke, most commonly lacunar infarcts 1-4
porencephalic cysts, often unilateral 1-4
CTA/MRA
Angiographic studies may demonstrate the presence of intracranial cerebral aneurysms, most commonly affecting the intracranial internal carotid artery or middle cerebral artery 1-4.
Treatment and prognosis
No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 2.
Differential diagnosis
General imaging differential considerations include:
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