Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Brain small vessel disease with hemorrhage

Brain small vessel disease with Axenfeld-Rieger anomaly is an autosomal recessive disorder characterized by cerebrl bleedings. Other clinical features include retinal arteriolar tortuosity, hypopigmentation of the fundus, and diffuse leukoencephalopathy. The disease can manifest in infantile hemiparesis. It is caused by mutations of the COL4A1 gene. Because of similar structure and function mutations of the COL4A2 genes may case the same clinical picture.


Several mutations of the same gene cause a more severe manifestation called Porencephaly.


In the management of the disorder anticoagulants are better avoided because of the risk to cause severe cerebral bleeding.


Hereditary neurological disorders
Alzheimer disease
Arts syndrome
Autosomal dominant cerebellar ataxia, deafness and narcolepsy
Autosomal recessive spastic paraplegia type 44
Brain malformations with urinary tract defects
Brain small vessel disease with hemorrhage
Brunner syndrome
Charcot-Marie-Tooth disease
Congenital insensitivity to pain with anhidrosis
Hereditary benign chorea
Hereditary distal motor neuron neuropathy type 5A
Hereditary muscle diseases
Hereditary sensory and autonomic neuropathy type 2A
Hereditary sensory neuropathy type 1E
Hypokalemic periodic paralysis 1
Hypomyelinating Leukodystrophy 2
Idiopathic basal ganglia calcification 1
Intellectual disability-severe speech delay-mild dysmorphism syndrome
Nemaline myopathy 5
Rett syndrome
Severe neonatal-onset encephalopathy with microcephaly
Spastic paraplegia 17 with amyotrophy of hands and feet
Susceptibility to glioma
Vascular dementia
X-linked syndromic mental retardation 13



Vahedi K et al. (2003) Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy.


Van Agtmael T et al. (2005) Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy.


Gould DB et al. (2006) Role of COL4A1 in small-vessel disease and hemorrhagic stroke.


Sibon I et al. (2007) COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke.


Vahedi K et al. (2007) Clinical and brain MRI follow-up study of a family with COL4A1 mutation.

Update: Sept. 26, 2018