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

• Best Macular Dystrophy
• Polymorphic Vitelline Macular Degeneration 
• Vitelliform Macular Dystrophy Type 2 (VMD2)

What is Best Vitelliform Macular Dystrophy? (Definition/Background Information)

• Best Vitelliform Macular Dystrophy (BVMD) is a slowly progressive form of macular degeneration
• It usually begins in childhood or adolescence, but age of onset and severity of vision loss can vary. Affected people first have normal vision, followed by decreased central visual acuity and distorted vision (metamorphopsia). Peripheral vision is not affected
• BVMD is characterized by atrophy of the retinal pigment epithelium and impaired central visual function. The retina is the back part of the eye that contains the specialized cells that respond to light, known as  photoreceptors
• BVMD is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has been reported. The condition is typically caused by mutations in the BEST1 gene; in a few cases the cause is unknown
• Treatment is symptomatic and involves the use of low vision aids, and direct laser treatment or photodynamic therapy. Newer treatment includes anti-VEGF agents (bevacizumab) and transcorneal electrical retinal stimulation

(Source: Best Vitelliform Macular Dystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Best Vitelliform Macular Dystrophy? (Age and Sex Distribution)

• Best Vitelliform Macular Dystrophy is a rare congenital disorder. The presentation of symptoms may occur during childhood or even later
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Best Vitelliform Macular Dystrophy? (Predisposing Factors)

• A positive family history may be an important risk factor, since Best Vitelliform Macular Dystrophy is an inherited condition
• Currently, no other risk factors have been clearly identified for BVMD

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 Best Vitelliform Macular Dystrophy? (Etiology)

Best Vitelliform Macular Dystrophy (BVMD) is caused by changes (mutations) in the BEST1 gene.

• This gene gives the body instructions for making a protein called bestrophin. Bestrophin acts as a channel that controls the movement of chloride ions within the retina
• It is thought that mutations in the BEST1 gene affect the shape of the channel and its ability to properly regulate the flow of chloride. However, it is unclear how exactly this relates to the specific features of BVMD
• Best Vitelliform Macular Dystrophy (BVMD) is most commonly inherited in an autosomal dominant manner, although a few cases with autosomal recessive inheritance have been reported
• Most people with BVMD have an affected parent, but some people have the condition as the result of a new mutation that occurred for the first time

(Source: Best Vitelliform Macular Dystrophy; 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.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Best Vitelliform Macular Dystrophy?

The signs and symptoms of Best Vitelliform Macular Dystrophy may include:

• Abnormal electroretinogram
• Macular dystrophy
• Reduced visual acuity

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

• Cystoid macular degeneration
• Metamorphopsia
• Visual impairment

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

• Abnormality color vision
• Choroideremia
• Visual field defect

(Source: Best Vitelliform Macular Dystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Best Vitelliform Macular Dystrophy Diagnosed?

• Best Vitelliform Macular Dystrophy (BVMD) may be diagnosed based on the findings on an exam of the fundus (the interior surface of the eye opposite the lens); an electrooculogram (EOG); and the family history
• An eye exam may include other tests as well. A fundus exam may show a typical yellow yolk-like macular lesion
• The EOG, which reflects the retinal pigmentary epithelium function, is the most diagnostic test for evaluating vitelliform macular dystrophy
• In the majority of the cases, a severe decrease occurs in light response, reflected by an Arden (light-peak/dark-trough) ratio of 1.1-1.5. (The normal Arden ratio is 1.8.) Carriers will also have an abnormal EOG result
• No correlation exists between EOG result and disease stage, visual acuity, or patient age. EOG results are usually symmetric for both eyes
• The family history in affected people is often consistent with either autosomal dominant or autosomal recessive inheritance
• Genetic testing may also be used to make a diagnosis of BVMD. A BEST1 mutation is detected in about 96% of affected people who have an affected family member
• In people with no family history of BVMD, the mutation detection rate ranges between 50-70%
• A mutation in BEST1 gene is more probable when a vitelliform lesion is accompanied by a reduced Arden ratio on EOG testing
• The exact type of genetic test ordered to confirm a diagnosis may depend on a person's ancestry, family history, and/or whether other eye disorders are also being considered

(Source: Best Vitelliform Macular Dystrophy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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 Best Vitelliform Macular Dystrophy?

The complications of Best Vitelliform Macular Dystrophy may include:

• Loss of vision
• Quality of life is affected

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

How is Best Vitelliform Macular Dystrophy Treated?

There is no specific treatment for Best Vitelliform Macular Dystrophy (BVMD) at this time.

• Low vision aids help affected people with significant loss of visual acuity
• Laser photocoagulation, photodynamic therapy, and anti-VEGF (vascular endothelial growth factor) agents such as bevacizumab have shown limited success in treating some of the secondary features of BVMD such as choroidal neovascularization (when abnormal blood vessels grow under the macula and retina)

(Source: Best Vitelliform Macular Dystrophy;Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Best Vitelliform Macular Dystrophy be Prevented?

Currently, Best Vitelliform Macular Dystrophy 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 Best Vitelliform Macular Dystrophy? (Outcomes/Resolutions)

• The prognosis of Best Vitelliform Macular Dystrophy 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

Additional and Relevant Useful Information for Best Vitelliform Macular Dystrophy:

Best Vitelliform Macular Dystrophy is also known by the following names:

• Best Disease
• Early-Onset Vitelliform Macular Dystrophy
• Juvenile-Onset Vitelliform Macular Dystrophy

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

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