Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

A rare genetic disorder affecting the retina, brain, and other organs

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant genetic disorder characterized by progressive degeneration of the small blood vessels in the retina, brain, and other organs. This condition leads to a variety of symptoms, including vision loss, neurological deficits, and systemic manifestations.

Genetics

RVCL-S is caused by mutations in the TREX1 gene, which is located on chromosome 3. The TREX1 gene encodes a DNA exonuclease that is involved in the degradation of DNA. Mutations in this gene lead to the accumulation of DNA fragments, which can trigger an inappropriate immune response and result in the damage of small blood vessels.

Location of the TREX1 gene on chromosome 3

Clinical Features

The clinical presentation of RVCL-S is highly variable, but it typically begins in adulthood, often between the ages of 20 and 40. The main features include:

Ocular Manifestations

- Retinal vasculopathy: Patients often experience progressive vision loss due to the degeneration of retinal blood vessels. This can lead to retinal detachment and macular degeneration.

Neurological Manifestations

- Cerebral leukoencephalopathy: This refers to the degeneration of white matter in the brain, which can cause a range of neurological symptoms such as headaches, cognitive decline, and stroke-like episodes.

Systemic Manifestations

- Systemic vasculopathy: The condition can affect other organs, leading to kidney disease, liver dysfunction, and hypertension.

Pathophysiology

The pathophysiology of RVCL-S involves the accumulation of DNA fragments due to defective TREX1 enzyme activity. This accumulation can activate the immune system, leading to inflammation and damage to the endothelial cells lining the small blood vessels. The resulting vasculopathy affects multiple organ systems, particularly the retina and brain.

Diagnosis

Diagnosis of RVCL-S is based on clinical evaluation, family history, and genetic testing to identify mutations in the TREX1 gene. Imaging studies such as MRI of the brain can reveal characteristic changes in white matter, supporting the diagnosis.

Management

There is currently no cure for RVCL-S, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. This may include: - Ophthalmologic care: Regular eye examinations and interventions to manage vision loss. - Neurological care: Monitoring and managing neurological symptoms, including the use of medications to control headaches and seizures. - Systemic management: Addressing systemic issues such as hypertension and organ dysfunction.

Prognosis

The prognosis for individuals with RVCL-S varies depending on the severity of symptoms and the organs affected. The condition is progressive, and life expectancy may be reduced due to complications such as stroke and organ failure.

Related pages

• Retinal disease
• Leukoencephalopathy
• Genetic disorder

Diagram of autosomal dominant inheritance