Genetic Implications

The inheritance pattern of Best disease is autosomal dominant. With such genetic conditions it is likely that there would be several affected individuals in successive generations in a family.
Genetic testing for Best disease is available in a few center around the world:

1. The Carver Laboratory at http://www.carverlab.org/request/offered.html. The cost is $161.10 for one test. 
2. For Israeli patients, genetic testing can be performed as part of a genetic research and is thus free of charge.

Please contact Dr. Dror Sharon for more details at: 02-6777112. 

The protein product of VMD2, bestrophin, has been localised to the basolateral plasma membrane of the RPE where it forms a component of a chloride channel responsible for maintaining chloride conductance across the basolateral membrane of the RPE. This chloride current regulates fluid transport across the RPE, and it has been suggested following optical coherence tomography of patients with Best disease, that impaired fluid transport in the RPE secondary to abnormal chloride conductance may lead to accumulation of fluid and/or debris between RPE and photoreceptors and between RPE and Bruch’s membrane, leading to detachment and secondary photoreceptor degeneration.

The variable expression of Best disease remains unexplained and other genes in addition to VMD2, and/or environmental factors may play a role.

Another form of macular degeneration, adult vitelliform macular dystrophy (AVMD) is often confused with Best disease. The age of onset in AVMD is later than in Best disease, and it lacks the typical course through different stages of macular disease seen in classical Best disease.

Mutations in the peripherin/RDS gene on chromosome 6p have been identified in AVMD. It has been proposed that mutations in peripherin/RDS are present in approximately 20% of patients with AVMD, which implies further genetic heterogeneity.