CARASIL

A rare genetic disorder affecting the brain's small blood vessels

CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare genetic disorder that affects the small blood vessels in the brain. It is characterized by a combination of neurological and non-neurological symptoms, including subcortical infarcts, leukoencephalopathy, alopecia, and spondylosis.

Genetics

CARASIL is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The condition is caused by mutations in the HTRA1 gene, which encodes a serine protease involved in the regulation of TGF-beta signaling.

Autosomal recessive inheritance pattern

Pathophysiology

The HTRA1 gene mutations lead to a loss of function of the HTRA1 protein, resulting in abnormal TGF-beta signaling. This disruption affects the integrity and function of the small blood vessels in the brain, leading to the characteristic features of CARASIL. The vascular changes result in ischemic events and white matter changes, contributing to the neurological symptoms.

Clinical Features

CARASIL typically presents in early adulthood, although symptoms can appear in adolescence. The main clinical features include:

• Neurological symptoms: Progressive dementia, pseudobulbar palsy, and ataxia are common. Patients may also experience stroke-like episodes due to subcortical infarcts.
• Alopecia: Early-onset hair loss is a distinctive feature of CARASIL, often occurring in the second or third decade of life.
• Spondylosis: Degenerative changes in the spine, particularly in the lumbar region, are frequently observed.

Diagnosis

The diagnosis of CARASIL is based on clinical evaluation, neuroimaging, and genetic testing. MRI scans typically reveal leukoencephalopathy and subcortical infarcts. Genetic testing can confirm the presence of mutations in the HTRA1 gene.

Management

There is currently no cure for CARASIL, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. Physical therapy, occupational therapy, and speech therapy may be beneficial for managing neurological symptoms. Regular monitoring and management of cardiovascular risk factors are also important.

Prognosis

The prognosis for individuals with CARASIL varies, but the condition is progressive and can lead to significant disability. The rate of progression and severity of symptoms can differ among affected individuals.

Related pages

• CADASIL
• Leukoencephalopathy
• Genetic disorders