Usher’s Syndrome

“People with Usher’s syndrome face a staggering number of obstacles each day, from safely getting around at night, to having a conversation with a friend.”

Brief Summary of Disease
People with Usher’s syndrome face a staggering number of obstacles each day, from safely getting around at night, to having a conversation with a friend. Usher’s syndrome is one of the most common diseases affecting both the auditory and visual systems, and is a leading cause of deaf-blindness in the Canadian population. ¹ Three major types of Usher syndrome (Type I, Type II, and Type III) exist, which are classified by the age of onset and severity of symptoms. The prevalence of Usher’s syndrome in the general population is around 3-6 in 100,000, though its frequency may be underestimated. ² Although there is no known cure for this disease, a number of potential treatments are currently being investigated.

Etiology & Pathology
The disease onset differs significantly, depending on whether the patient is affected by Type I, Type II, or Type III Usher’s syndrome. Gene mutations that cause Usher’s syndrome are related to normal balance, hearing, and vision. ¹ Visual impairment is caused by a disease called retinitis pigmentosa (RP), which affects the light-sensing cells of the retina. The hearing loss is sensorineural, meaning that it is caused by abnormalities of the inner ear. At least 11 causative genes have been identified so far. These genes provide instructions for proteins that are essential to the development and maintenance of the cells of the inner ear and retina. Mutations in these genes can cause gradual cellular deterioration, leading to a decline in visual and auditory acuity. ³

“As the disease progresses, visual acuity and color vision begin to deteriorate, which may eventually result in total blindness.”

Symptoms
The earliest and most apparent symptom of Usher syndrome is hearing loss. Most individuals with Type I Usher’s syndrome are born with profound hearing loss, with progressive vision loss becoming apparent in childhood. ¹ Children typically seem “clumsy” and have difficulty with activities requiring balance. Patients with Type II Usher’s syndrome have a more gradual onset of symptoms, with moderate hearing loss and later onset of night vision problems. In Type III Usher’s syndrome, the onset of symptoms often does not occur until the late teenage years. As the disease progresses, visual acuity and color vision begin to deteriorate, which may eventually result in total blindness.⁴ Some children also experience difficulties with motor skills and balance, due to problems in the vestibular system caused by damage to the hair cells of the inner ear. ¹

Diagnosis
Usher’s syndrome is diagnosed based on vision, hearing and balance tests. A perturbation in all three systems is highly suggestive of the disease. To confirm the presence of RP, a physical examination of the retina and electroretinogram may be used. Further, a test called an electronystagmogram measures involuntary eye movement, and is used to verify whether there is damage to the inner ear, which may cause dizziness and vertigo. ³ Genetic testing may also be used to confirm the presence of Usher’s syndrome. ¹

Because hearing difficulties are often the earliest and most apparent symptom of Usher’s syndrome, a common misdiagnosis for this disease is nonsyndromic deafness. Unfortunately, this has led to an underestimation of the prevalence of Usher’s syndrome. The disease itself may go undiagnosed until the child or parent notices night vision loss. ¹

“ Early diagnosis would have positive implications for educational planning, genetic counseling, and treatment. ”

Children
The average age of diagnosis of Usher syndrome is around 10-12 years of age, although symptoms may manifest earlier. ³ All children born in Canada undergo a hearing screen at birth, allowing for hearing problems to be diagnosed early. Recent studies have shown that DNA testing for Usher syndrome is feasible, and that it could potentially be incorporated into the newborn screening program. ² Early diagnosis would have positive implications for educational planning, genetic counseling, and treatment. ⁵

A child with Usher’s syndrome requires comprehensive care from a number of medical specialists. ⁶ Examples of treatments currently being used are cochlear implants, mobility training, and communication services such as Braille instruction. These approaches can drastically change an affected child’s ability to interact with the world, and improve their quality of life. ⁴

Current Research
At present, there is no known cure for Usher’s syndrome, although there has been significant interest in developing gene therapies for this disease. Gene therapy involves introducing a healthy copy of the mutated gene into the patient’s cells, allowing for the non-functional proteins to be replaced. ⁴ A group of researchers has recently been able to restore hearing and balance in one mouse model of Usher’s syndrome. ⁸ However, developing gene therapies for this disease has proven difficult, as the protein-protein interactions that lead to symptoms of Usher’s syndrome are not fully understood. ⁷ Further research into the etiology of Usher’s syndrome will allow us to work towards a cure for this disorder.

Relevant Resources
The Usher Syndrome Coalition

They work to provide support and information to families and individuals impacted by Usher Syndrome. Their goal is to raise awareness and accelerate research, as well as to help bridge the gap between researchers and families.

The Usher Syndrome Coalition

A non-profit organization, that raises awareness and funds for Usher syndrome. They host several events throughout the year to educate the public about this disease as well as to raise funds for research in the hopes of find a cure for Usher syndrome.

Works Cited:

1. Samuelson, S. & Zahn, J. Usher’s syndrome. Ophthalmic Paediatr Genet 11, 71–76 (1990).,

2. Kimberling, W. J. et al. Frequency of Usher Syndrome in Two Pediatric Populations: Implications for genetic screening of Deaf and Hard of Hearing Children. Genet Med 12, 512–516 (2010).

3. Mathur, P. & Yang, J. Usher syndrome: hearing loss, retinal degeneration and associated abnormalities. Biochim Biophys Acta 1852, 406–420 (2015).

4. Williams, D. S. Usher syndrome: animal models, retinal function of Usher proteins, and prospects for gene therapy. Vision Res 48, 433–441 (2008).

5. Lentz, J. & Keats, B. J. Usher Syndrome Type I. in GeneReviews® (eds. Adam, M. P. et al.) (University of Washington, Seattle, 1993).

6. Kwiecień, S., Sulak, R. & Szaflik, J. Usher’s syndrome--case report. Klin Oczna 110, 384–386 (2008).

7. Dammeyer, J. Children with Usher syndrome: mental and behavioral disorders. Behav Brain Funct 8, 16 (2012).

8. Emptoz, A. et. al.Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G. Proc Natl Acad Sci 114, 9695-9700 (2017).

Cite This Article:

Wowk L., Chan G., Palczewski K., Zhang B., Lewis K., Ho J. Usher’s Syndrome. Illustrated by C. Qian. Rare Disease Review. January 2020. DOI:10.13140/RG.2.2.30618.80325.