Retinal vasculopathy with cerebral leukoencephalopathy (RVCL)

Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) is a genetic disease that causes blockages in small blood vessels, especially in the eyes and brain. Over time, RVCL also causes damage to other parts of the body, including the kidneys, liver, and bones. It’s exceedingly rare—fewer than 50 families around the world have been known to be affected by the disease. Because it can be mistaken for other conditions, like multiple sclerosis or vasculitis, it’s important to be evaluated by a team of providers who are experienced in diagnosing RVCL.

Penn Medicine is an international leader in studying, understanding, and treating this rare condition. Our specialists have extensive knowledge about the disease and can provide you and your family members with a diagnosis and the latest treatments. Through our research, we’re leading the way in developing a therapy that targets the gene involved in RVCL, and we’re working on creating personalized medications that can slow the progression of symptoms. Families from across the globe travel here to be examined and treated by our specialized team of rheumatologists, neurologists, ophthalmologists, and genetic counselors.

The disease doesn’t usually cause symptoms until around ages 40 to 50, though you might experience the effects of RVCL earlier or later. Once they appear, symptoms tend to gradually get worse and may include:

• Fingers and toes that change color and become swollen, numb, and painful in cold weather, known as Raynaud’s syndrome
• Blind spots in your vision
• Fatigue
• Stroke
• Memory loss
• Weakness, numbness, or other stroke-like symptoms

Over time, you may develop hypertension, chronic kidney disease, liver disease, glaucoma, blindness, gastrointestinal bleeding, bone disease, or dementia. If you were assigned female at birth, having RVCL puts you at higher risk of early-onset breast cancer. People with RVCL also die at younger ages than people without the disease, so it’s important to treat these complications as soon as they occur.

Changes (mutations) in a specific region of a gene called TREX1 cause the disease. Typically, people have two full copies of TREX1, but those with RVCL have one full-length copy and one that’s shorter than usual. These gene changes are passed down in families. If you have a parent with TREX1 gene mutations, you have a 50 percent chance of having the disease.

Your doctor will ask about your symptoms, your health history, and the medical history of your family members. RVCL is diagnosed by testing for the TREX1 gene mutations. You’ll meet with genetic counselors who are experts in RVCL before your genetic testing. The earlier you’re tested and diagnosed, the sooner you can be evaluated for complications and get treatment for them. You might also have blood tests and brain imaging to look at how the disease is affecting you.

There’s no cure for RVCL, though researchers are working hard to find one. Until then, your doctor can treat your symptoms and complications with medications and therapies. You’ll need regular checkups that include specialized eye exams to take images of your retina, physical exams, cognitive testing, and brain imaging. Your doctor will also monitor your liver and kidney function.

If you have the gene mutations that cause RVCL and you’re planning a family, talk to your doctor about your options. A procedure called preimplantation genetic testing (PGT) allows people with RVCL to use in vitro fertilization and choose embryos without TREX1 mutations to transfer to the uterus. This testing can help you make informed decisions and protect your children from having the disease.

Penn Medicine conducts continuous research into RVCL therapies. We have a laboratory dedicated to developing gene therapy to fully correct the mutated gene that causes the disease. We’re also using innovative technology to develop personalized medicines that block the mutated protein that’s encoded by the TREX1 gene, which may help halt the disease or slow its progression. You may have an opportunity to participate in a clinical trial at Penn Medicine to advance these and other RVCL treatments.

In addition to our extensive research in this field, our doctors and genetic counselors are here to provide advanced care and support to you and your family. We’re also partnering with institutions worldwide to create an international RVCL registry, which can help facilitate multinational clinical research and allow families to connect. Our experts are doing everything they can to improve the lives of families affected by this inherited condition.