Best disease
Best disease, also known as Best's vitelliform macular dystrophy, is a rare hereditary disorder that primarily affects the macula, the central area of the retina responsible for sharp vision. It is caused by mutations in the BEST1 gene, which is located on chromosome 11. The condition often presents in children and can lead to partial or complete blindness, with symptoms manifesting in multiple stages. Initial stages may not significantly impact vision, but as the disease progresses, lesions can form and ultimately result in scar tissue, impairing visual acuity.
Best disease has been observed across diverse ethnic groups, affecting both males and females equally, although it often runs in families. Diagnosis typically occurs between the ages of three and fifteen, and while there is currently no cure, treatment options focus on managing symptoms and providing support through visual aids. Notably, recent research has shown promise in genetic therapies that may one day offer more effective interventions.
Best disease
ALSO KNOWN AS: Best’s vitelliform macular dystrophy (early-, juvenile-, and adult-onset); BVMD; vitelline dystrophy; vitelliruptive degeneration; vitelliform macular degeneration; macular degeneration, polymorphic vitelline; early-onset macular degeneration
DEFINITION: Best disease is a rare hereditary disorder that causes macular dystrophy. The disease destroys the macula, a very small area in the center of the retina. Best disease occurs most often in children and usually results in partial or complete blindness. The disorder is caused by a mutation in the BEST1 gene, also known as the VMD2 gene, on chromosome 11.
Risk Factors
The only known risk factor for Best disease is a family history of BEST1gene mutation. Best disease affects children of European, African, and/or Hispanic backgrounds. Male and female children are equally affected. Diet and activity do not appear to influence disease progression.
Etiology and Genetics
Best disease is an autosomal dominant disorder. It has been mapped to the long arm of chromosome 11 (11q12–q13). The BEST1gene encodes the protein bestrophin-1, an integral membrane protein located in the retinal pigment epithelium (RPE). The protein plays a role in regulating voltage-dependent calcium channels and ocular development.
Pathology of the BEST1 gene mutation remains unknown. However, one study demonstrated a change on the pathway that affects the light peak on the electrooculogram, a diagnostic test. Despite the disease effect on the RPE, blindness most likely comes from scarring of the macula, a part of the retina that contains millions of cone cells that provide central vision, sharp visual acuity, and color vision.
There are more than 120 known mutations of the BEST1 gene, resulting in many ocular phenotypes. Although symptoms of Best disease are erratic, the disorder appears to have complete genetic penetrance, and most affected children have some visual disturbances. However, there is also evidence for genetic nonpenetrance: In some cases, vision remains unaffected. Symptoms of Best disease neither progress nor decrease from one generation to the next, indicating that the disorder has no genetic anticipation.
Best disease passes from one generation to the next via just one parent who carries the mutated BEST1 gene. Each child of an affected parent has a 50 percent chance of also carrying the mutation. There does not appear to be a standard correlation between the gene and resultant symptoms (genotype-phenotype correlation). Usually, one or more family members may be affected in each generation, although it is not uncommon for Best disease to skip a generation.
Symptoms
The disease has six stages of progression. Sight is usually not affected in the first three stages, and the child may have 20/20 to 20/50 visual acuity for several years. During the previtelliform phase (stage 1), there is abnormal electrical potential during eye positioning and movements. In stage 2, yellow round spots (“egg-yolk” lesions) are evident on eye examination. Absorption of the lesions is identified in stage 3. Surprisingly, sight is affected not as the lesions continue to grow but rather when the lesions break up (stage 4), causing a “scrambled egg” appearance or scarring of the macula. During stage 5, vision is significantly affected, and subretinal scarring occurs in stage 6.
Best disease takes on different characteristics depending on the child. The disease may not progress, and vision loss may be barely noticeable. The disease may also progress rapidly, and vision may deteriorate markedly. Vision loss first occurs as blurring (decreased acuity) and object distortion (metamorphopsia). Children often have an easier time seeing objects that are far away than those that are close (hyperopia, or farsightedness). Peripheral vision and dark adaptation are usually not affected. Best disease is often bilateral, although it may occur in just one eye.
Screening and Diagnosis
Several tests may be used to identify Best disease. The electroretinogram measures the retina's electrical response when stimulated by light. The electrooculogram evaluates poorly defined macular lesions. The diagnosis of Best disease is unusual in that the results of the electroretinogram are nearly normal, while the electrooculographic findings are abnormal.
Best disease is usually diagnosed between three and fifteen years of age, with many children being diagnosed around six years of age. The disease has also been known to occur first in adulthood.
Treatment and Therapy
There is no known treatment for this condition. Direct laser photocoagulation may be used for revascularization and bleeding. Genetic counseling is available at clinics that specialize in macular diseases or low vision. Various services, including lighting, visual aids, and visual assistance, are also available to help people with low vision or sight loss.
In 2023, researchers at the University of Wisconsin-Madison's School of Medicine and Public Health made a breakthrough discovery that may lead to an effective genetic treatment for Best disease and similar conditions. Their work revealed it was possible to deliver the gene-editing tool CRISPR base editor to retinal cells via silica nanocapsules. This approach successfully restored the function of a key protein responsible for controlling the flow of potassium ions in retinal tissue, which allowed the retina's light-detecting cells to function normally.
Prevention and Outcomes
Cessation of cigarette smoking may help the retina revascularize.
Bibliography
Agarwal, Anita. Gass' Atlas of Macular Diseases. 5th ed. 2 vols. Philadelphia: Saunders, 2012. Print.
Bitner, Hanna, et al. "Frequency, Genotype, and Clinical Spectrum of Best Vitelliform Macular Dystrophy: Data from a National Center in Denmark." American Journal of Ophthamology 154.2 (2012): 403–12. Print.
Boon, C. J., et al. “Clinical and Genetic Heterogeneity in Multifocal Vitelliform Dystrophy.” Archives of Ophthalmology 125.8 (2007): 1100–1106. Print.
Kliegman, Robert M., et al. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders, 2011. Print.
MacDonald, Ian M., and Thomas Lee. "Best Vitelliform Macular Dystrophy." GeneReviews. Ed. Roberta A. Pagon et al. Seattle: U of Washington, Seattle, 1993–2014. NCBI Bookshelf. Natl. Center for Biotechnology Information, 12 Dec. 2013. Web. 16 July 2014.
Remington, Lee Ann. Clinical Anatomy and Physiology of the Visual System. 3rd ed. St. Louis: Butterworth, 2012. Print.
Van Sluijs, Sharon M. "New Gene-Editing Technique Holds Potential for Treating Childhood Blindness." University of Wisconsin-Madison School of Medicine and Public Health, 29 Sept. 2023, www.med.wisc.edu/news/gene-editing-technique-childhood-blindness. Accessed 9 Sept. 2024.
Yanoff, Myron, and Jay S. Duker, eds. Ophthalmology. 4th ed. Philadelphia: Saunders, 2014. Print.