See what it is like to live with Usher 3.

Usher syndrome has 3 types, each causing a different mix of health problems. Type 1 and 2 are most common in the US and account for up to 95% of Usher syndrome cases. [Millan JM. et al. 2011; Jouret G. et al. 2019].

Type 1: deafness at birth, vision loss by midlife, and balance problems.

Type 2: childhood hearing loss, vision loss by midlife, and normal balance.

Type 3: childhood hearing loss, vision loss by midlife, and normal balance.

Type 3 is the most rare - it is estimated to affect less than 3% of people with Usher Syndrome overall, which itself has a prevalence of approximately 1 in 6,000 to 1 in 8,000 people worldwide.

Usher syndrome causes deafness or hearing loss and retinitis pigmentosa (RP). RP breaks down cells in the retina, causing loss of peripheral and night vision, and eventually tunnel vision. Children with RP may have difficulty in the dark and tripping over objects, while adults may struggle with tasks such as driving, walking, and reading.

Unlike other forms of Usher syndrome, USH3 is usually associated with normal hearing at birth. A distinguishing feature of USH3 is the wide spectrum of nonlinear progressive hearing impairment, which ranges from a near normal to a severe audiometric phenotype. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Patients show high degree of variability in the type and degree of hearing loss. However, the highest progression of hearing loss occurs during the first two decades of life [Plantinga RF. et al. 2005].

Vision loss in USH3 is caused by retinitis pigmentosa, and occurs as the light-sensing cells of the retina gradually deteriorate and eventually atrophy. In USH3, vision loss generally develops in late childhood or adolescence and progresses to adulthood.

Night vision loss begins first, followed by gradual development of tunnel vision. In some cases, vision is further impaired by cataracts. Legal blindness often occurs by midlife. However, many people retain some central vision throughout their lives.

Most individuals with USH3 have normal to near-normal balance, but some develop balance problems with age.

Usher syndrome type III (Usher 3) is caused by genetic mutations that affect the production or function of proteins involved in hearing and vision. Specifically, mutations in the CLRN1 gene are known to cause Usher 3 syndrome. The condition is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Currently, there is no cure for Usher syndrome type III (Usher 3). However, in 2016, the Usher III initiative has located a molecule (BF844) that shows potential in mitigating hearing loss. They are currently working to push the drug development towards Phase 1 clinical trials.

As reported in the journal Nature Chemical Biology, BF844 is a small molecule compound capable of mitigating hearing loss in a mouse model of Usher III [Alagramam KN. et al. 2016]. In theory, BF844 also has the potential to attenuate both hearing and vision loss in Usher III patients. BF844 was discovered by Initiative researchers in 2016.

Presently, there is no cure or specific treatment approved for USH3 patients. Treatments are urgently needed to prevent or delay the progression of hearing and vision impairments and restore quality of life for individuals with USH3.

Many therapies (including gene therapy, cellular therapy, and small molecules) are being tested for different types of Usher syndrome, but all are in early stages of development.

The current treatments involve managing hearing, vision, and balance problems. For the hearing loss, patients generally have bilateral cochlear implants to restore hearing. However, optimal hearing is not achieved and the implants need to be adjusted frequently.

There is no treatment for the vision loss in this disease, which continues to progress with age due to the gradual irreversible loss of retinal cells. Vision problems are managed by education, lifestyle adaptation, and visual aids.