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

• HERNS Syndrome

What is Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome? (Definition/Background Information)

• Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke (HERNS) Syndrome is a rare genetic condition that affects the vascular endothelium (the inner lining of the arteries and blood vessels). Specifically, the small blood vessels of the brain (microangiopathy); retina (vascular retinopathy); and kidneys are affected
• Signs and symptoms may include progressive adult onset vision loss, psychiatric disturbances, stroke-like episodes, neurologic decline, and kidney disease
• HERNS Syndrome is inherited in an autosomal dominant manner
• The term retinal vasculopathy with cerebral leukodystrophy (RVCL) has recently been adopted to include HERNS, cerebroretinal vasculopathy (CRV), and hereditary vascular retinopathy (HVR)
• Historically, these 3 conditions have been considered distinct. Genetic studies have shown that these 3 conditions are likely variations of RVCL and are caused by mutations in the TREX1 gene

(Source: Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome? (Age and Sex Distribution)

• Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome is a rare congenital disorder, with very few cases reported in the medical literature 
• The presentation of symptoms occur in adulthood, typically in an affected individual’s 30s-40s
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for HERNS Syndrome

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 Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome? (Etiology)

• Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke is caused by mutation(s) in the TREX1 gene
• The condition is inherited in an autosomal dominant manner 

Autosomal dominant inheritance: 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 Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome?

The signs and symptoms of Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome may include:

• Presence of cerebral microvasculopathic lesions: Some individuals go on to develop mass lesions, predominantly involving the right frontal lobe. These lesions are often mistaken for tumors
• Abnormality of the musculature of the lower limbs
• Abnormality of the periventricular white matter
• Apraxia
• Behavioral abnormality
• Central nervous system degeneration
• Dementia
• Elevated erythrocyte sedimentation rate
• Elevated hepatic transaminases
• Hematuria
• Hemiparesis
• Lower limb hyperreflexia
• Macular edema
• Migraine
• Pigmentary retinal degeneration
• Progressive forgetfulness
• Progressive visual loss
• Proteinuria
• Punctate vasculitis skin lesions
• Raynaud phenomenon
• Retinal exudate
• Seizures
• Stroke
• Telangiectasia
• Vasculitis in the skin
• Visual impairment

(Source: Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome Diagnosed?

Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome 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
• Molecular genetic testing to check for or confirm causative TREX1 gene mutation(s)

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 Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome?

The complications of Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome may include:

• Progressive loss of vision, blindness
• Psychological problems
• Kidney malfunction
• Anxiety and depression
• Risk of falls and injury
• Paralysis

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

How is Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome Treated?

There is no cure for Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include:

• Aspirin
• Laser treatment of eyes to prevent retinal hemorrhage
• Continuous use of corticosteroids to reduce/control brain swelling (edema)

How can Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome be Prevented?

Currently, Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke 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 Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome? (Outcomes/Resolutions)

• The prognosis of Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome is generally poor, since the condition is progressive in nature
• The majority of affected individuals succumb to the disorder within 10 years of onset of symptoms
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke Syndrome:

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

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