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Disease Profile

Autosomal recessive bestrophinopathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Retinopathy, Burgess-Black type

Categories

Eye diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 139455

Definition
A rare retinal dystrophy, characterized by central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG).

Epidemiology
The prevalence of ARB is still unknown; to date less than 20 cases have been described in the world literature.

Clinical description
ARB generally manifests in the first 2 decades of life, but patients may also first become symptomatic as late as the fifth decade of life. Most affected individuals initially present with central visual loss (visual acuity ranging from 20/200 to 20/25) and are usually mildly to highly hyperopic. Additional ocular findings may include short axial length with angle-closure glaucoma, amblyopia, anterior uveitis, strabismus, and color vision defects. Choroidal neovascularization (CNV) has been described in one case. Leukokoria and esotropia have also been reported.

Etiology
ARB is caused by compound heterozygous or homozygous mutations in the BEST1 gene (11q12) which encodes the chloride ion channel bestrophin-1 (expressed in the retinal pigment epithelium (RPE)). Mutations in BEST1 reduce or abolish the activity of the channel. It has been proposed that ARB may represent the null phenotype of bestrophin-1 in humans.

Diagnostic methods
Diagnosis of ARB relies on ophthalmologic examination, familial history and visual electrophysiology revealing an abnormal full-field ERG (reduced amplitudes and delayed implicit times of the rod and cone ERGs). Absent or severe reduction in EOG light rise (Arden ratio= 1.0) is commonly observed. Irregularity of the RPE throughout the posterior fundus, often with scattered punctate flecks (observed by autofluorescence imaging) is also found. Optical coherence tomography (OCT) imaging shows retinal edema, serous subretinal fluid, subretinal yellowish lesions and scars. Classic vitelliform lesions are not present. Fluorescein angiography reveals widespread patchy areas of hyperfluorescence and signs of mild perivascular leakage in the peripheral retina. Cystoid macular edema may be observed. Diagnosis is confirmed by the genetic screening of BEST1.

Differential diagnosis
Differential diagnosis includes Stargardt disease, familial drusen, Best vitelliform macular dystrophy, age-related macular degeneration (see these terms), central serous chorioretinopathy and chorioretinitis.

Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.

Management and treatment
Management of ARB is mainly symptomatic and includes treatment of amblyopia, surgical strabismus correction, prophylactic laser (YAG) peripheral iridotomy to prevent angle closure and treat glaucoma, and intravitreal bevacizumab for the treatment for CNV. Cystoid macular edema may be treated with oral administration of acetazolamide. Gene therapy may offer a possible treatment for ARB in the future. Close monitoring of ARB patients is recommended, including repeated gonioscopy to judge the risk of angle closure.

Prognosis
Onset of vision loss in patients has been reported to vary between the ages of 4 to 40, and is coincident with initial presentation.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Decreased lightand dark-adapted electroretinogram amplitude
0000654
Hypermetropia
Farsightedness
Long-sightedness

[ more ]

0000540
Reduced visual acuity
Decreased clarity of vision
0007663
Retinal flecks
0012045
Retinal pigment epithelial atrophy
0007722

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Autosomal recessive bestrophinopathy. Click on the link to view a sample search on this topic.