Hereditary cerebral small vessel disease and stroke
Christian Baastrup Søndergaard1, Jørgen Erik Nielsen2, Christine Krarup Hansen1
1Department of Neurology, Copenhagen University Hospital, Bispebjerg, Denmark.
Clinical Neurology and Neurosurgery
|March 4, 2017
Summary
Hereditary cerebral small vessel diseases, often causing early stroke, require molecular genetic testing for diagnosis. This review guides clinicians on identifying these rare genetic disorders.
Area of Science:
- Neurology
- Genetics
- Vascular Medicine
Background:
- Cerebral small vessel disease (CSVD) has hereditary forms in ~5% of cases.
- Characterized by MRI findings like lacunar infarcts and white matter hyperintensities.
- Several monogenic disorders causing CSVD and stroke are known.
Purpose of the Study:
- To guide molecular genetic testing decisions in patients with CSVD and stroke.
- To review genetics, pathology, clinical features, imaging, and diagnosis of specific monogenic disorders.
- To highlight the importance of genetic counseling and diagnostic challenges.
Main Methods:
- Systematic review of monogenic hereditary CSVDs.
- Description of CADASIL, CARASIL, COL4A mutations, RVCL, Fabry disease, HCHWA, and FOXC1 mutations.
- Analysis of clinical presentation, neuroimaging, and diagnostic criteria.
Main Results:
- Monogenic CSVDs often present with early stroke, migraine, mood disturbances, dementia, and gait issues.
- Extra-cerebral manifestations (eye, kidney microangiopathy) can occur.
- Molecular genetic analysis is the definitive diagnostic standard.
Conclusions:
- Timely molecular genetic testing is crucial for diagnosing hereditary CSVDs.
- Early identification aids genetic counseling and potential targeted therapies (e.g., enzyme replacement in Fabry disease).
- Treatment options for most hereditary CSVDs remain limited.
