Autosomal recessive bestrophinopathy

Autosomal recessive - en

Autosomal Recessive Bestrophinopathy (ARB) is a rare genetic disorder affecting the retina, characterized by reduced visual acuity, macular dystrophy, and a predisposition to the development of vitreous cysts. It is caused by mutations in the BEST1 gene, which encodes the bestrophin-1 protein, a chloride channel that is essential for normal retinal function. This condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms and Diagnosis

The symptoms of ARB typically manifest in early adulthood, but can vary widely in severity and onset. Common symptoms include reduced central vision, distorted vision (metamorphopsia), and light sensitivity (photophobia). The hallmark of ARB on fundus examination is a disrupted or irregular retinal pigment epithelium (RPE) layer, often accompanied by the presence of yellowish subretinal deposits. Advanced imaging techniques such as Optical Coherence Tomography (OCT) and Fluorescein angiography (FA) are crucial in diagnosing ARB, revealing characteristic changes in the retinal structure and function.

Genetics

ARB is caused by mutations in the BEST1 gene, located on chromosome 11q12.3. The BEST1 gene encodes the protein bestrophin-1, which is predominantly expressed in the RPE and plays a critical role in the regulation of chloride ions across the cell membrane. Mutations in BEST1 lead to a dysfunctional chloride channel, disrupting the ionic balance necessary for normal RPE and photoreceptor function. To date, over 200 mutations in the BEST1 gene have been identified, many of which are associated with ARB and other related retinal dystrophies.

Treatment and Management

There is currently no cure for ARB, and treatment is primarily supportive and aimed at managing symptoms. Low vision aids and adaptive technologies can help individuals maximize their remaining vision. Regular monitoring by an ophthalmologist is important to detect and manage complications, such as the development of choroidal neovascularization (CNV), which can be treated with intravitreal injections of anti-VEGF medications. Genetic counseling is recommended for affected individuals and their families to understand the inheritance pattern and risks for future generations.

Prognosis

The prognosis for individuals with ARB varies depending on the severity of the retinal changes and the presence of complications. While the disease tends to progress slowly, it can lead to significant visual impairment over time. Early detection and intervention can help manage symptoms and improve the quality of life for those affected.

Research Directions

Research into ARB and other retinal dystrophies is ongoing, with efforts focused on understanding the underlying genetic mechanisms and developing potential treatments. Gene therapy, aimed at correcting the genetic mutations in the retina, holds promise for the future. Additionally, advances in stem cell therapy and artificial vision technologies may offer new avenues for restoring vision in individuals with ARB.