'Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome

被引：101

作者：

Alamowitch, S. ^{[1
]}

Plaisier, E. ^{[2
,3
,4
]}

Favrole, P. ^{[1
]}

Prost, C. ^{[5
]}

Chen, Z. ^{[4
]}

Van Agtmael, T. ^{[6
]}

Marro, B. ^{[7
]}

Ronco, P. ^{[2
,3
,4
]}

机构：

[1] Tenon Hosp, AP HP, Stroke Unit, Dept Neurol, Paris, France

[2] Univ Paris 06, UMRS702, F-75252 Paris 05, France

[3] Tenon Hosp, Dept Nephrol, Paris, France

[4] INSERM, U702, Paris, France

[5] Avicenne Hosp, AP HP, Dept Dermatol, Bobigny, France

[6] Univ Glasgow, Fac Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland

[7] Tenon Hosp, AP HP, Dept Radiol, Paris, France

来源：

NEUROLOGY | 2009年 / 73卷 / 22期

基金：

英国医学研究理事会;

关键词：

RETINAL ARTERIOLAR TORTUOSITY; SMALL-VESSEL DISEASE; INTRACRANIAL ANEURYSMS; COLLAGEN-IV; STROKE; LEUKOENCEPHALOPATHY; HEMORRHAGE; CADASIL; NEPHROPATHY; DYSGENESIS;

D O I：

10.1212/WNL.0b013e3181c3fd12

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 COL4A1 mutations. Neurology (R) 2009; 73: 1873-1882

引用

页码：1873 / 1882

页数：10

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