Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome

Alamowitch, S., Plaisier, E., Favrole, P., Prost, C., Chen, Z., Van Agtmael, T. , Marro, B. and Ronco, P. (2009) Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology, 73(22), pp. 1873-1882. (doi:10.1212/WNL.0b013e3181c3fd12)

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Publisher's URL: http://dx.doi.org/10.1212/WNL.0b013e3181c3fd12

Abstract

Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. The aim of this study was to describe the cerebrovascular phenotype of HANAC.

Methods: Detailed clinical data were collected in 14 affected subjects from the 3 families. MRI and magnetic resonance angiography (MRA) were performed in 9 of them. Skin biopsies were analyzed by electron microscopy in affected subjects in the 3 families.

Results: Only 2 of 14 subjects had clinical cerebrovascular symptoms: a minor ischemic stroke at age 47 years and a small posttraumatic hemorrhage under anticoagulants at age 48 years. MRI-MRA showed cerebrovascular lesions in 8 of 9 studied subjects (mean age 39.4 years, 21–57 years), asymptomatic in 6 of them. Unique or multiple intracranial aneurysms, all on the carotid siphon, were observed in 5 patients. Seven patients had a CSVD characterized by white matter changes (7/7) affecting subcortical, periventricular, or pontine regions, dilated perivascular spaces (5/7), and lacunar infarcts (4/7). Infantile hemiplegia, major stroke, and porencephaly were not observed. Skin biopsies showed alterations of basement membranes at the dermoepidermal junction associated with expansion of extracellular matrix between smooth vascular cells in the arteriolar wall.

Conclusion: The cerebrovascular phenotype in hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome associates a cerebral small vessel disease and a large vessel disease with aneurysms of the carotid siphon. It is consistent with a lower susceptibility to hemorrhagic stroke than in familial porencephaly, suggesting an important clinical heterogeneity in the phenotypic expression of disorders related to COL4A1mutations.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chen, Dr Zhonghua and Van Agtmael, Dr Tom
Authors: Alamowitch, S., Plaisier, E., Favrole, P., Prost, C., Chen, Z., Van Agtmael, T., Marro, B., and Ronco, P.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Neurology
Publisher:Lippincott Williams & Wilkins
ISSN:0028-3878
ISSN (Online):1526-632X
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
471511Collagen type IV in vascular biologyTom Van AgtmaelMedical Research Council (MRC)G0601268Institute of Cardiovascular and Medical Sciences