COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage.
OBJECTIVE
Recently COL4A1, a gene encoding the type IV collagen alpha1 chain, has been found to be involved in families with autosomal-dominant porencephaly and infantile hemiparesis. In addition to neonatal stroke, some family members had experienced, during adulthood, spontaneous intracerebral hemorrhages (ICHs) and leukoencephalopathy, suggestive of underlying small-vessel disease of the brain. We now report a patient with sporadic, recurrent ICHs and a novel COL4A1 mutation.


METHODS
We performed a clinical and genetic study of a 25-year-old-patient with an 8-year history of recurrent ICHs.


RESULTS
This young, normotensive patient with a history of infantile hemiparesis had experienced, since the age of 17, recurrent, spontaneous, deep ICHs occurring during sports activities. He became severely disabled. Brain magnetic resonance imaging showed ventricular enlargement, diffuse white-matter abnormalities, and newly appearing, deep, silent microbleeds. Extensive investigations found no cause. There was no family history of stroke or infantile hemiparesis. A novel COL4A1 mutation (G805R) was identified.


CONCLUSIONS
The clinical spectrum of COL4A1 mutations includes recurrent ICHs in association with diffuse leukoencephalopathy in young adults, even in the absence of a family history of infantile hemiparesis or ICH. In addition to birth trauma, anticoagulant use, and head trauma previously reported, sports activities may be a precipitating factor of ICHs in persons with COL4A1 mutations.
Vahedi
Katayoun
K
AP-HP, Service de Neurologie, Hôpital Lariboisière, Paris, France. katayoun.vahedi@lrb.aphp.fr
Kubis
Nathalie
N
Boukobza
Monique
M
Arnoult
Minh
M
Massin
Pascale
P
Tournier-Lasserve
Elisabeth
E
Bousser
Marie-Germaine
MG
D000328:Adult; D002543:Cerebral Hemorrhage / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D006429:Hemiplegia / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D012008:Recurrence
D024141:Collagen Type IV