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Cerebral small vessel disease with hemorrhagic stroke related to COL4A1 mutation: A case report
Bevinahalli N Nandeesh1, Parayil Sankaran Bindu2, Gayathri Narayanappa1
1Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Insights
This study details a rare COL4A1 gene mutation causing cerebral small vessel disease (SVD) and stroke in a young woman. The findings highlight the genetic disorder
Area of Science:
- Genetics
- Neurology
- Ophthalmology
Background:
- Cerebral small vessel disease (SVD) contributes significantly to stroke, particularly in younger individuals.
- Hereditary disorders affecting small cerebral blood vessels are key etiological factors in SVD.
- Mutations in the COL4A1 gene are linked to various conditions, including stroke, myopathy, and glaucoma.
Observation:
- A rare case of stroke in an 18-year-old intellectually disabled female is presented.
- Radiological findings included basal ganglia microbleeds, periventricular white matter changes, and a porencephalic cyst.
- Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly.
Findings:
- Autopsy confirmed multiple hemorrhagic brain lesions.
- Histology showed thickened small cerebral vessels with basement membrane disruption, confirmed by collagen type IV alpha 1 immunohistochemistry and electron microscopy.
- A missense COL4A1 mutation affecting a glycine residue was identified in the patient.
Implications:
- This case expands the known clinicopathological spectrum of COL4A1-related cerebral SVD.
- It illustrates the presentation of hemorrhagic stroke with porencephaly, intellectual disability, and Axenfeld-Rieger anomaly in the young.
- The findings underscore the clinical heterogeneity associated with COL4A1 genetic disorders.
Abstract:
Stroke is a major cause of mortality and morbidity with a wide variety of etiological risk factors. Cerebral small vessel disease (SVD) is an important cause of stroke in the young with several hereditary disorders affecting these small blood vessels. Mutations in the COL4A1 gene (COL4A1) have been shown to be associated with a broad range of disorders including hemorrhagic stroke, myopathy, glaucoma and others. We report a rare case of stroke in an intellectually disabled 18-year-old girl with radiological evidence of basal ganglia microbleeds, periventricular white matter signal changes and porencephalic cyst. Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly. At autopsy there were hemorrhagic lesions at multiple sites within the brain. Histology revealed thickened small-caliber vessels which demonstrated disruption and fragmentation of the basement membrane by collagen type IV alpha 1 immunohistochemistry and by electron microscopy. A missense COL4A1 mutation involving glycine residue was detected in the patient. The present case illustrates the clinicopathological spectrum of COL4A1-related cerebral SVD presenting as hemorrhagic stroke in the young with porencephaly, intellectual disability, and Axenfield-Rieger anomaly and thus adds to the clinical heterogeneity of this genetic disorder.
