cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 is a condition that primarily affects the small blood vessels in the brain, leading to changes visible on MRI and a predisposition to strokes. It is caused by pathogenic variants in the HTRA1 gene, which disrupt normal vascular functions in the cerebral white matter. Although precise prevalence estimates are not well established, this condition is recognized as an uncommon cause of cerebrovascular events that typically manifests in adulthood. Men and women may be affected, and the clinical picture often evolves over time with cumulative neurological complications.

The clinical presentation is characterized by consistent radiological findings, with nearly all affected individuals showing hyperintensity of cerebral white matter on MRI. Other common features include status cribrosum and lacunar strokes, observed in the majority of affected individuals. Many patients also experience gait disturbances, transient ischemic attacks, and strokes, while a subset encounter cognitive impairment, seizures, dementia, and headaches. Not all individuals experience all of these features, and severity varies considerably, with the neurological elements such as cognitive impairment underscoring the central nervous system involvement.

This condition is caused by mutations in the HTRA1 gene, which plays an important role in maintaining the integrity of the small blood vessels in the brain. Inherited in an autosomal dominant pattern, only one copy of the altered gene is sufficient to increase susceptibility to the disease. That not all individuals who inherit the mutation will experience the full spectrum of symptoms, as there is variable expressivity, with clinical severity and specific manifestations differing among affected family members.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address issues such as stroke prevention, blood pressure management, and rehabilitation for motor or cognitive difficulties. Patients are encouraged to discuss available options with their healthcare team, and genetic counseling is recommended to help guide family planning and clarify recurrence risks.

The long‐term outlook for individuals with this condition varies widely, with the clinical course ranging from periods of relative stability to episodes of stroke and progressive neurological decline. With current standards of care, many individuals manage their symptoms into adulthood, although the overall trajectory is highly variable. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for guidance regarding long-term management and family planning.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility, as further research is expected to enhance understanding and management of the disease.