Small vessel disease (SVD) is a condition that affects the tiny blood vessels deep within the brain. These vessels supply oxygen and nutrients to brain tissue. When damaged, it can lead to a range of neurological problems. The question of whether this condition is hereditary is complex, as SVD can arise from various factors. This article explores small vessel disease and the specific circumstances under which it can be hereditary.
What is Small Vessel Disease?
Small vessel disease describes damage to the brain’s smallest arteries, arterioles, capillaries, and venules. This damage reduces blood flow, depriving brain tissue of oxygen and nutrients. Over time, this can lead to white matter lesions, lacunar infarcts (small strokes), or microbleeds.
Common causes for SVD include long-standing high blood pressure, diabetes, high cholesterol, and advancing age. These factors can stiffen and narrow the small vessels, impairing function. Symptoms often develop gradually and can include problems with memory, thinking, balance, and walking. Some individuals may experience transient ischemic attacks (TIAs) or strokes.
Genetic Forms of Small Vessel Disease
While many cases of small vessel disease are linked to common risk factors, specific genetic mutations can directly cause hereditary forms. One of the most recognized genetic forms is Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). This condition is caused by mutations in the NOTCH3 gene, which provides instructions for a receptor protein found on the surface of vascular smooth muscle cells. The NOTCH3 gene mutation leads to abnormal protein deposits in the walls of small blood vessels throughout the body, particularly in the brain.
Another hereditary form is Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL). This rare condition results from mutations in the HTRA1 gene, which produces an enzyme involved in regulating signaling by the TGF-β family of proteins. Mutations in HTRA1 disrupt the integrity of the small blood vessels, leading to characteristic brain changes. Beyond CADASIL and CARASIL, other less common monogenic forms of SVD exist, involving genes like COL4A1 and TREX1, each contributing to distinct patterns of vascular damage. These genetic forms highlight that SVD is not always a consequence of lifestyle but can be predetermined by an individual’s genetic makeup.
Inheritance Patterns and Genetic Testing
Genetic forms of small vessel disease are passed down through families based on their specific inheritance pattern. CADASIL, for instance, follows an autosomal dominant inheritance pattern. Only one copy of the altered NOTCH3 gene is sufficient to cause the disorder. An affected individual has a 50% chance of passing the mutation to each child.
In contrast, CARASIL is inherited in an autosomal recessive manner. For this condition to develop, an individual must inherit two copies of the mutated HTRA1 gene, one from each parent. Individuals who carry only one copy of the mutated gene are unaffected but can pass the gene to their children. Genetic counseling is recommended for families with a history of hereditary SVD to understand these patterns and assess personal risk. Genetic testing involves analyzing a person’s DNA, usually from a blood sample, to identify specific gene mutations. This testing can confirm a diagnosis, identify unaffected carriers, and provide valuable information for family planning.
Management and Prevention in Hereditary Cases
Managing hereditary small vessel disease focuses on controlling symptoms and preventing complications, as there are currently no cures for most genetic forms. Medical interventions aim to manage associated risk factors that can worsen the disease, such as controlling blood pressure and cholesterol levels. Individuals are advised to adopt healthy lifestyle modifications, including regular physical activity, a balanced diet, and avoiding smoking, to support overall vascular health.
Early diagnosis through genetic testing allows for proactive monitoring and intervention. Regular neurological assessments and brain imaging, such as MRI scans, help track disease progression and identify new lesions. While specific treatments targeting the genetic defects are under investigation, comprehensive care involves a multidisciplinary approach to address cognitive impairments, mood disturbances, and physical limitations. This ongoing management helps improve the quality of life for those living with a hereditary form of small vessel disease.
References
Small Vessel Disease. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/health-information/disorders/small-vessel-disease. Accessed 2025-07-27.
Cerebral small vessel disease. Stroke Association. Available at: https://www.stroke.org.uk/what-is-stroke/types-of-stroke/cerebral-small-vessel-disease. Accessed 2025-07-27.
CADASIL. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/health-information/disorders/cadasil. Accessed 2025-07-27.
CARASIL. National Library of Medicine, Genetics Home Reference. Available at: https://medlineplus.gov/genetics/condition/carasil/. Accessed 2025-07-27.
Genetic cerebral small vessel disease. National Library of Medicine, National Center for Biotechnology Information. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900996/. Accessed 2025-07-27.