COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review.
OBJECTIVE
A number of single gene disorders can cause cerebral small vessel disease. Mutations in the COL4A1 gene encoding the type IV collagen alpha 1 chain, which are already associated with porencephaly and infantile hemiparesis, have been recently recognized as a further monogenic cause of small vessel disease that can present in adulthood.


METHODS
We performed a systematic review of published data from 1966 to January 8, 2010 to characterize the features of small vessel disease seen with COL4A1 mutations.


RESULTS
We identified a total of 52 mutation carriers. A history of stroke was reported in 9 subjects (17.3%); in 6 cases it was attributable to subcortical hemorrhage and in 3 cases it was attributable to lacunar infarction. Stroke often occurred as first presentation of the disease, with a mean age of onset of 36.1 (SD, 12.95; range, 14-49). Hemorrhages, often recurrent, have been associated with physical trauma and activity and anticoagulant therapy. Brain imaging showed frequent leukoaraiosis (63.5%), microbleeds that are usually subcortical (52.9%), lacunar infarction (13.5%), and dilated perivascular spaces (19.2%). Extensive leukoaraiosis was seen in a number of asymptomatic adult mutation carriers. Asymptomatic intracranial aneurysms were common (44.4% of 18 with angiography). Migraine (with and without aura) was reported in 10 subjects, with a mean age at onset of 31.7. Systemic features are also frequent, affecting the eye (10/21, 47.6%), kidney (15.4%), and muscle (15.4%).


CONCLUSIONS
COL4A1 is a further cause of familial vasculopathy and may present with stroke, ischemic as well as hemorrhagic, in adult life and with radiological features of leukoaraiosis and microbleeds.
Lanfranconi
Silvia
S
Clinical Neuroscience, St George's University of London, London, UK.
Markus
Hugh S
HS
D000328:Adult; D002561:Cerebrovascular Disorders / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
C547475:COL4A1 protein, human; D024141:Collagen Type IV