What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (ADRVCL)
• Hereditary Cerebroretinal Vasculopathy
• Retinopathy, Vascular, with Cerebral and Renal Involvement, and Raynaud and Migraine Phenomena

What is Retinal Vasculopathy with Cerebral Leukodystrophy? (Definition/Background Information)

• Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) is a rare, genetic condition that primarily affects the central nervous system
• Symptoms begin in adulthood (usually in the 40s) and may include loss of vision, mini-strokes, and dementia. Death can sometimes occur within 10 years of the first symptoms appearing
• RVCL is inherited in an autosomal dominant manner and is caused by mutations in the TREX1 gene
• Treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause
• RVCL is now considered to include the following 3 conditions which were previously thought to be distinct:
  • Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke (HERNS)
  • Cerebroretinal Vasculopathy (CRV)
  • Hereditary Vascular Retinopathy (HVR)

(Source: Retinal Vasculopathy with Cerebral Leukodystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Retinal Vasculopathy with Cerebral Leukodystrophy? (Age and Sex Distribution)

• Retinal Vasculopathy with Cerebral Leukodystrophy is a rare disorder
• The presentation of symptoms typically occur during middle-age (with onset in the 5^th decade)
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Retinal Vasculopathy with Cerebral Leukodystrophy? (Predisposing Factors)

• A positive family history may be an important risk factor, since Retinal Vasculopathy with Cerebral Leukodystrophy can be inherited
• Currently, no other risk factors have been clearly identified for RVCL

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Retinal Vasculopathy with Cerebral Leukodystrophy? (Etiology)

• Retinal Vasculopathy with Cerebral Leukodystrophy is inherited in an autosomal dominant manner and is caused by mutations in the TREX1 gene

(Source: Retinal Vasculopathy with Cerebral Leukodystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Retinal Vasculopathy with Cerebral Leukodystrophy?

The signs and symptoms of Retinal Vasculopathy with Cerebral Leukodystrophy may include:

• Abnormality of the musculature of the lower limbs
• Abnormality of the periventricular white matter
• Central nervous system degeneration
• Dementia
• Elevated erythrocyte sedimentation rate
• Elevated hepatic transaminases
• Limb pain
• Lower limb hyperreflexia
• Macular edema
• Pigmentary retinal degeneration
• Progressive forgetfulness
• Punctate vasculitis skin lesions
• Raynaud phenomenon
• Retinal exudate
• Retinal hemorrhage
• Telangiectasia
• Vasculitis in the skin

Very frequently present symptoms in 80-99% of the cases:

• Focal white matter lesions
• Leukodystrophy
• Visual impairment

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the retinal vasculature
• Apraxia
• Behavioral abnormality
• Dysarthria
• Hemiparesis
• Mental deterioration
• Migraine
• Progressive visual loss
• Retinopathy
• Seizures
• Stroke

Occasionally present symptoms in 5-29% of the cases:

• Ataxia
• Glomerulopathy
• Hematuria
• Micronodular cirrhosis
• Nephropathy
• Proteinuria

(Source: Retinal Vasculopathy with Cerebral Leukodystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Retinal Vasculopathy with Cerebral Leukodystrophy Diagnosed?

Retinal Vasculopathy with Cerebral Leukodystrophy is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Retinal Vasculopathy with Cerebral Leukodystrophy?

The complications of Retinal Vasculopathy with Cerebral Leukodystrophy may include:

• Intellectual impairment
• Kidney dysfunction
• Vision loss

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Retinal Vasculopathy with Cerebral Leukodystrophy Treated?

There is no cure for Retinal Vasculopathy with Cerebral Leukodystrophy, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Retinal Vasculopathy with Cerebral Leukodystrophy be Prevented?

Currently, Retinal Vasculopathy with Cerebral Leukodystrophy may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Retinal Vasculopathy with Cerebral Leukodystrophy? (Outcomes/Resolutions)

• The prognosis of Retinal Vasculopathy with Cerebral Leukodystrophy is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis. However, RVCL is known to be fatal in some cases

Additional and Relevant Useful Information for Retinal Vasculopathy with Cerebral Leukodystrophy:

• Retinal Vasculopathy with Cerebral Leukodystrophy is also known by the following names: Cerebroretinal Vasculopathy (CRV)

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/