Pathology
An overview of autosomal dominant inheritance of genes

Best disease: A rare genetic disorder of the eye



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An overview of autosomal dominant inheritance of genes
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"Best disease: A rare genetic disorder of the eye"
Caption: An overview of autosomal dominant inheritance of genes
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Best disease is a genetic disorder known more formally as early onset vitelliform macular dystrophy. It is a rare autosomal dominant disorder first described in 1905 by a German ophthalmologist, Dr. Franz Best. Vitelliform means “egg-like,” which describes the yolk-like appearance of the lesion that first appears in the eye as early as 3 years of age (95 percent of all patients with the genetic disorder have lesions by age 40 according to University of Iowa Health Care). The lesion is in the macula, a part of the retina at the back of the eye. Because this area is responsible for sharp, central vision (ability to read, drive and recognize faces), this part of sight is the first to deteriorate as the lesion develops over the years.

Causes of vitelliform macular dystrophy

The vitelliform lesion is caused by a mutation in the VMD2 gene (also known as BEST1, on the long arm of chromosome 11), which encodes a chlorine channel present in the retinal pigment epithelium and moves the bestrophin protein as outline at the National Library of Medicine's Genetics Home Reference. Roughly three-quarters of mutations are inherited. The defective channels allow the accumulation of a yellow pigment called lipofuscin in the pigment layer of the retina. Subretinal hemorrhage is also sometimes seen, which can further affect visual acuity. The condition is also associated with other retinal defects, such as loss of photoreceptors.

Symptoms of Best disease

Best disease can be asymptomatic, though mild vision loss, particularly loss of acuity, is likely at early stages, with moderate vising loss in later stages. Cases are usually discovered upon examination - eye exams tend to uncover pseudohypopyon, an accumulation of lipid fluid in the eye that mimics the appearance of infection, and bilateral fundus lesions can be visualized on the retina. The electrooculogram will be abnormal with a low Arden ratio (light/dark balance), even in so-called carriers (as a dominant disorder, any presence of the mutation will have some manifestation). Choroidal neovascular membrane, the abnormal growth of blood vessels in the eye, may be present in addition to hemorrhage.

Five to six stages of progression are recognized for the appearance of vitelliform lesions in the disease depending on how symptoms are grouped:

  • Previtelliform - normal vision, subtle eye changes seen
  • Vitelliform - typical lesion, some vision loss
  • Pseudohypopyon - lipofuscein accumulation, no additional effect on vision
  • Vitelleruptive - lesion breaks up, may cause additional vision loss
  • Atrophic - late stage with loss of visual acuity, retinal atrophy
  • Choroidal neovascular - atrophy causes a scar that severely affects vision

Many individuals do not progress beyond the early stages of vitelliform macular dystrophy, and even at later stages vision is well maintained in most patients.

Treatment of vitelliform lesions

Treatment consists potentially of surgery for the hemorrhage, though most cases resolve on their own with a return of vision that was lost due to the hemorrhage. Choroidal neovascular membrane can be treated with laser therapy. Intravitreal injections of bevacizumab, an anti-tumor drug (brand name: Avastin) may be prescribed or anti-VEGF therapy, but no direct therapy for the lesions is currently available. 

Most people with Best disease had a parent that was also affected by the condition. Be sure to discuss any vision loss with your eye doctor, as well as any concerns about a family history of progressive vision loss or blindness. If you have vitelliform macular dystrophy and are concerned about the risk of passing it on, genetic testing is available. Discuss your options with your doctor.

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ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://emedicine.medscape.com/article/1227128-overview
  • InfoBoxCallToAction ActionArrowhttp://webeye.ophth.uiowa.edu/eyeforum/cases/case11.htm
  • InfoBoxCallToAction ActionArrowhttp://ghr.nlm.nih.gov/condition/vitelliform-macular-dystrophy
  • InfoBoxCallToAction ActionArrowhttp://www.stlukeseye.com/Conditions/cnvm.html
  • InfoBoxCallToAction ActionArrowhttp://eyewiki.aao.org/Best_Disease
  • InfoBoxCallToAction ActionArrowhttp://www.ncbi.nlm.nih.gov/books/NBK1167/