Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is an autosomal dominant angiopathy caused by mutations in the TREX1 gene (three-prime repair exonuclease 1). RVCL-S is a rare disorder and can be challenging to diagnose. Patients are therefore often misdiagnosed. Worldwide, less then 25 families in which RVCL-S occurs are known, of which three live in the Netherlands. Most likely, this is an underestimation of the real number of patients.
RVCL-S was called Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL). Before this, the names Hereditary Vascular Retinopathy (HVR), Cerebroretinal Vasculopathy (CRV), Hereditary Endotheliopathy with Retinopathy, Nefropathy and Stroke (HERNS), and Hereditary Systemic Angiopathy (HSA) were used.
The clinical presentation of RVCL-S and its course are highly variable between and within families. The most important signs and symptoms are vascular retinopathy and focal and global brain dysfunction, including stroke, non-ischemic events, cognitive decline, migraine, seizures and psychiatric complaints. Often kidney dysfunction and elevated liver enzymes, anemia, hypertension and Raynaud’s phenomenon and subclinical hypothyroidism occur.
RVCL-S is a progressive disorder, but the rate of progression varies between individuals. The first complaints often start between the age of 30 and 40 years. The first symptom is often visual impairment, while cognitive decline often occurs in later stages of the disease. Symptoms can remain stable during long periods, slowly worsen or suddenly worsen greatly. Life expectancy is decreased for RVCL-S patients.
Treatment of RVCL-S
There is currently no treatment to cure RVCL-S or to delay disease progression. Given the rarity of the disorder, there is unfortunately limited prove for effective treatments for the different manifestations of the disorder.
An appointment with a clinical geneticist with knowledge about RVCL-S is recommended. At-risk family members should also be offered an appointment to discuss the advantages and disadvantages of genetic testing. Unlike many hereditary neurological disorders there can be health gain by testing for RVCL-S in pre-symptomatic at-risk relatives. For instance, timely treatment of retinopathy can help prevent blindness.
When the diagnosis has been made, regularly scheduled controls are advised to try to prevent damage and complications. The following procedures are recommended to determine if treatment or additional testing is required:
- Ophthalmological evaluation
- Neurological evaluation
- MRI brain
- Blood pressure measuring
- Laboratory tests (kidney function, thyroid function, liver enzymes and blood count)
More information about RVCL-S
Further research into RVCL-S is necessary to improve our understanding of the disease mechanism and to, ultimately, find a cure for RVCL-S. Therefore, at the LUMC we conduct both fundamental and clinical research into RVCL-S. We collaborate with different specialists in the LUMC and with other hospitals and research centers both nationally and internationally.
More information about our research and an overview of our most recent publications can be found here.