Clinical Guidance

For most BEST1 variants, genotype-phenotype correlations have not been demonstrated. However, a few missense variants have been associated with a milder phenotype:

• A family with a substitution had late-onset visual failure (age 40-50 years) .

• A family with had late-onset small vitelliform lesions .

• described affected individuals and families with the variant and late-onset disease with a distinct pattern of fundus autofluorescence. This variant was previously associated with mild disease .

Other observations:

Source: GeneReviews — "Bestrophinopathies"

Penetrance

BVMD shows high but reduced (70%) penetrance, especially when electrooculogram is used as evidence of clinical expression. Individuals heterozygous for a BEST1 variant associated with ARB are generally clinically unaffected . Nomenclature Other terms used to refer to BVMD include Best disease, early-onset vitelliform macular dystrophy, juvenile-onset vitelliform macular dystrophy, and polymorphic vitelline macular degeneration.

Source: GeneReviews — "Bestrophinopathies"

Diagnostic Criteria

No consensus diagnostic criteria for bestrophinopathies have been published.

Suggestive Findings

A bestrophinopathy should be suspected in individuals with following the ophthalmologic findings and electrophysiologic studies by phenotype, and family history. Ophthalmologic findings by phenotype

Source: GeneReviews — "Bestrophinopathies"

Differential Diagnosis

Best vitelliform macular dystrophy (BVMD) is the second most common hereditary macular dystrophy. The most common heritable juvenile-onset macular dystrophy is Stargardt disease. Although the cause of adult-onset vitelliform macular dystrophy (AVMD) in most individuals is unknown, this phenotype is observed in the spectrum of bestrophinopathies and with heterozygous pathogenic variants in PRPH2 (encoding peripherin-2) (OMIM 179605), IMPG1 (OMIM 616151) and IMPG2 (OMIM 616152). Choroidal neovascularization is an acquired disorder.

Source: GeneReviews — "Bestrophinopathies"

Management Guidelines

No clinical practice guidelines for bestrophinopathies have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a bestrophinopathy, the evaluations summarized below (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Ophthalmologic examination, including best-corrected visual acuity, fundus examination, fundus photographs, and spectral-domain optical coherence tomography (SD-OCT) to determine the stage of disease

• Consultation with a low vision specialist/clinic as needed

• Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of bestrophinopathies in order to facilitate medical and personal decision making

Treatment of Manifestations

Low vision aids benefit those individuals with significantly reduced visual acuity. In the United States (US), educational issues for children with visual impairment can be addressed in the following:

Source: GeneReviews — "Bestrophinopathies"

Clinical Guidance

Cessation of smoking helps prevent neovascularization of the retina .

Source: GeneReviews — "Bestrophinopathies"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Bestrophinopathies"

Surveillance Guidelines

Ophthalmologic examination (including best-corrected visual acuity, visual fields, and SD-OCT) should be performed annually to monitor the progression of the fundus lesions and to evaluate for coincident development of choroidal neovascularization (CNV). In children, annual examinations are important in preventing the development of amblyopia, especially if there is a significant difference in the best-corrected visual acuity of one eye. A trial of conventional patching therapy of the better-seeing eye may be able to determine if amblyopia is present. Affected individuals should be advised to see their ophthalmologist in the event of decreased vision or metamorphopsia (straight lines appearing wavy), which could be signs of CNV. In some cases, affected individuals can be advised to use an Amsler grid for self-evaluation.

Source: GeneReviews — "Bestrophinopathies"