IllnessBestrophinopathies, differential diagnosis

NGS +

Bestrophin-1 protein functions as a cell membrane channel in the retinal pigment epithelium. More than 100 BEST1 mutations have been identified in patients with BEST vitelliform macular dystrophy, i.e., the so-called Best disease as an early form in contrast to the adult form (OMIM153700). Age-related macular degeneration is one of the most common causes of vision loss in the elderly in developed countries. Subtle abnormalities indicating changes in vision can occur as early as the forties-fifties. Distorted vision and vision loss usually become apparent about 20 years later and worsen progressively. There are two main forms of age-related macular degeneration: the dry form and the wet form. The dry form accounts for nearly 90% and is characterized by yellowish deposits/drusen under the retina and vision loss. It slowly worsens to the advanced stage of dry macular degeneration, geographic atrophy, with severe vision loss. In up to 15% of affected individuals, the dry form progresses to the wet form, which is characterized by the growth of fragile blood vessels beneath the macula. Blood and fluid leak from these vessels, resulting in severe vision loss. It appears that a combination of genetic and environmental factors is often responsible for the development of age-related macular degeneration. BEST1 gene mutations can also cause a rare autosomal dominant vitreoretinochoroidopathy (OMIM193220). Many affected individuals have an abnormally curved microcornea of shallow anterior chamber, rod-cone dystrophy and posteroior staphyloma (OMIM193220). These individuals may develop glaucoma or cataract; some of these patients also show degeneration of the vitreous or choroid. Autosomal recessive bestrophinopathy (611809) is also caused by mutations in the BEST1 gene and results in progressive vision loss, perhaps representing one extreme of the phenotypic spectrum with vitelliform macular dystrophy at the other end. Finally, BEST1 gene mutations are rarely found in retinitis pigmentosa [concentric] (613194) and several other ocular diseases such as nanophthalmos. The molecular genetic yield is not precisely known. A negative DNA test result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1167/

• Alias: BEST1 adult-onset vitelliform macular dystrophy (BEST1)
• Alias: Morbus Best, Best disease
• Alias: Retinopathie Typ Burgess-Black
• Best vitelliform macular dystrophy (BEST1)
• Bestrophinopathy, AR (BEST1)
• Macular dystrophy, patterned, 1 (PRPH)
• Macular dystrophy, vitelliform, 2 (BEST1)
• Macular dystrophy, vitelliform, 3 (PRPH)
• Macular dystrophy, vitelliform, 4 (IMPG1)
• Macular dystrophy, vitelliform, 5 (IMPG2)
• Vitreoretinochoroidopathy AD (BEST1)