Genomic coordinate (human 11:61,949,821 BEST1) & (mouse 19:9,962,538 Best1).
Cytoband (human 11q12.3 BEST1) & (mouse 19qA Best1).
Here I present 🎁: “Best-Vitelliform Macular-Dystrophy“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (VMD2) icd10=H35.54
Best-vitliform macular-dystrophy (BVMD) is an inherited, progressive eye disease, usually diagnosed in childhood, that causes fatty yellow pigment (lipofuscin) to accumulate under the macula. Key symptoms include blurred or distorted central vision, though peripheral vision is typically spared. It is caused by mutations in the BEST1 gene, affecting retinal pigment epithelium (RPE) cells. While no cure exists, treatments like anti-VEGF, laser, or photodynamic therapy can manage complications.
Key Details and Progression
Stages: The disease progresses from an egg-yolk-like lesion (vitelliform stage) to a “scrambled egg” appearance, which can lead to scarring and vision loss.
Prognosis: The prognosis is generally good, with many patients maintaining functional vision, including reading and driving, in at least one eye.
Inheritance: It is primarily autosomal dominant, meaning a child of an affected parent has a 50% chance of inheriting the gene mutation.
Diagnosis: A hallmark of the disease is a severely reduced light peak/dark trough ratio on electrooculogram (EOG) testing.
Differences from Adult-Onset
While Best Disease typically starts in childhood, a related form called “adult-onset vitelliform macular dystrophy” appears between ages 40–60, usually has smaller lesions, and exhibits a normal EOG.
Best vitelliform-macular dystrophy is an inherited macular degeneration affecting the retinal pigment epithelium (RPE) and photoreceptors in the macula. It typically begins in childhood or adolescence and gradually reduces central vision.
Genetic Basis
Primary gene: BEST1 (Bestrophin-1)
Cytoband location: 11q13
Inheritance pattern: Autosomal dominant
BEST1 encodes a calcium-activated chloride channel in the retinal pigment epithelium.
Mutation consequences:
Impaired ion transport across RPE
Abnormal fluid and lipofuscin accumulation
Formation of the vitelliform (“egg-yolk”) lesion
Classic Ophthalmic Appearance
Characteristic lesion:
Yellow, round macular deposit
Resembles egg yolk (vitelliform)
This deposit consists mainly of:
lipofuscin
photoreceptor debris
RPE metabolic products
Clinical Stages
Pre-vitelliform stage
Fundus appears nearly normal
Electro-oculogram abnormal
Vitelliform stage
Classic egg-yolk lesion in macula
Vision often still good
Pseudohypopyon stage
Material settles inferiorly (fluid level)
Vitelliruptive stage
“Scrambled egg” appearance
Lesion begins breaking apart
Atrophic stage
RPE and photoreceptor loss
Reduced central vision
Diagnostic Hallmarks
Electro-oculogram (EOG)
Markedly abnormal Arden ratio
Optical Coherence Tomography (OCT)
Subretinal vitelliform material
RPE dysfunction
Fundus autofluorescence
Strong signal from lipofuscin accumulation
Genetic testing
Confirms BEST1 mutation
Symptoms:
Common early signs:
Mild blurred central vision
Metamorphopsia (distorted lines)
Difficulty reading
Peripheral vision is usually preserved.
Human–Mouse Genetics
Human:
BEST1 — cytoband 11q12.3
Mouse Homolog:
Best1 gene — mouse chromosome 19
This murine locus participates in retinal pigment epithelium ion transport, paralleling the human macular dystrophy pathway.
Related Disorders (BEST1 spectrum)
Mutations in the same gene can produce:
Adult-onset vitelliform macular dystrophy
Autosomal recessive bestrophinopathy
Retinitis pigmentosa–like phenotypes
Conceptual Physiological Pathway
Cellular level:
RPE ion transport → fluid balance → photoreceptor metabolism
When BEST1 chloride channel fails:
RPE transport failure↓
lipofuscin accumulation↓
vitelliform lesion↓
photoreceptor degeneration.
Although the diagnosis of Best disease is often made during the childhood years, it is more frequently made much later and into the sixth decade of life. In addition, the typical egg yolk-like lesion is present only during a limited period in the natural evolution of the disease; later, the affected area becomes deeply and irregularly pigmented and a process called ‘scrambling the egg’ occurs, at which point the lesion may appear as a ‘bull’s eye.’ The disorder is progressive and loss of vision may occur. A defining characteristic of Best disease is a light peak/dark trough ratio of the electrooculogram (EOG) of less than 1.5, without aberrations in the clinical electroretinogram (ERG). Even otherwise asymptomatic carriers of BEST1 mutations, as assessed by pedigree, will exhibit an altered EOG. Histopathologically, the disease has been shown to manifest as a generalized retinal pigment epithelium (RPE) abnormality associated with excessive lipofuscin accumulation, regions of geographic RPE atrophy, and deposition of abnormal fibrillar material beneath the RPE, similar to drusen. Occasional breaks in the Bruch membrane with accompanying neovascularization have also been reported, although Best disease is not noted for extensive choroidal neovascularization. Many of these features are also found in age-related macular degeneration.
Bestrophin-1 (BEST1) is a protein encoded by the BEST1 gene that primarily acts as a calcium-activated anion channel in the retinal pigment epithelium (RPE). It is essential for maintaining vision by transporting chloride ions, maintaining retinal homeostasis, and supporting photoreceptor health. Mutations cause bestrophinopathies, including Best disease.
There is evidence that Best-vitliform macular-dystrophy is caused mutation in the bestrophin-1 (BEST1) gene encoded on genomic coordinate 11:61,949,821 and cytoband 11q12.3 in humans.
