Vitelliform macular dystrophy

Vitelliform macular dystrophy is a genetic eye disorder that can cause progressive vision loss. This disorder affects the retina, which is a specialized light-sensitive tissue that lines the back of the eye. Specifically, vitelliform macular dystrophy disrupts cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces.

Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision and may experience blurry or distorted vision. Vitelliform macular dystrophy does not affect side (peripheral) vision or the ability to see at night.

Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; however, the onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in middle age, and tends to cause relatively mild vision loss. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination.

Vitelliform macular dystrophy is a rare disorder; its incidence is unknown.

Mutations in the BEST1 and PRPH2 genes cause vitelliform macular dystrophy.

Mutations in the BEST1 gene are responsible for Best disease. Changes in either the BEST1 or PRPH2 gene can cause the adult-onset form of vitelliform macular dystrophy; however, less than a quarter of cases result from mutations in these two genes. In most cases, the cause of the adult-onset form is unknown.

The BEST1 gene provides instructions for making a protein called bestrophin. Although its exact function is uncertain, this protein likely acts as a channel that controls the movement of negatively charged chlorine atoms (chloride ions) into or out of cells in the retina. Mutations in the BEST1 gene probably lead to the production of an abnormally shaped channel that cannot regulate the flow of chloride. Researchers have not determined how these malfunctioning channels are related to the buildup of lipofuscin in the macula and progressive vision loss.

The PRPH2 gene provides instructions for making a protein called peripherin 2. This protein is essential for the normal function of light-sensing (photoreceptor) cells in the retina. Mutations in the PRPH2 gene disrupt the structures in these cells that contain light-sensing pigments, leading to vision loss. It is unclear why PRPH2 mutations affect only central vision in people with adult-onset vitelliform macular dystrophy.

Read more about the BEST1 and PRPH2 genes.

Best disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

The inheritance pattern of adult-onset vitelliform macular dystrophy is uncertain. Some studies have suggested that it may be inherited in an autosomal dominant pattern. Many affected people, however, have no history of the disorder in their family and only a small number of affected families have been reported.