Usher syndrome, named after ophthalmologist Charles Usher, is a hereditary genetic disorder that mainly causes hearing and vision loss. Approximately 4 to 17 per 100,000 people have usher syndrome, and usher syndrome makes up approximately 50-percent of all inherited deaf-blindness cases.
Usher syndrome is inherited as an autosomal recessive disorder. “Autosomal” is where both men and women have an equal chance of inheriting and passing down, whereas “recessive” means that two copies of the mutated gene must be inherited for the condition to appear. If only one faulty gene is inherited from one parent and a normal gene is inherited from the other, the child may become a carrier of usher syndrome. However, the child would not develop usher syndrome themselves, rather, the different mutated genes inherited determine what type of usher syndrome is developed.
There are 3 types of usher syndrome, simply named type 1, type 2, and type 3. Type 3 usher syndrome has the mildest symptoms, with mild progressive hearing loss starting to develop in adolescence and retinitis pigmentosa (RP). RP defines a group of inherited vision disorders that all cause degeneration in the retina, developing anytime from the teenage years to mid 30s, leading to legal blindness during midlife. Type 2 usher syndrome has similar visual problems as type 3 usher syndrome, as problems in night vision and adolescent peripheral vision are found in both types. What differentiates the two is that type 2 causes moderate to severe hearing loss in both ears at birth. Symptoms of type 1 usher syndrome, the most severe of the 3 types, consists of acute hearing loss in both ears at birth, and the onset of RP by age 10. However, cases exist with vision loss appearing in children younger than 10. Type 1 and 2 usher syndrome make up approximately 95% of all usher syndrome cases in the US.
While vitamin A supplementation can delay degeneration of the retina, currently there is no known cure to RP. However, recent research and testing organized by researchers from the University of Maryland School of Medicine (UMSOM), the National Institutes of Health’s National Eye Institute (NEI), and National Institute on Deafness and Other Communication Disorders (NIDCD) suggest a new method that could improve vision in people with type 1 usher syndrome.
One of the potentially mutated genes involved in type 1 is the PCDH15 gene, which encodes the blueprints for the creation of a protein called protocadherin-15. PCDH15 serves two main functions. Firstly, it assists in the movement of light-dark cycles between the different parts of the light-detecting photoreceptors of the eye. Additionally, PCDH15 is also essential for recycling retinoids, molecules that are critical for the functioning of eye tissue. The researchers at these institutes found that mice with type 1 usher syndrome had lower retinoid levels than mice without usher syndrome. This led to the testing of a retinoid drug for the mice with usher syndrome, and what resulted was an increase in electrical activity in the eyes of both youth and adult mice. This demonstrates that the drug was effective in improving vision function. While tests on humans have not been performed yet, these new findings move us in the right direction towards discovering a cure for the thousands of people suffering from type 1 usher syndrome.