Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder that causes your vision to get worse over time. It is the most common condition that affects both hearing and vision.

There are three types of Usher syndrome:

• People with type I are deaf from birth and have severe balance problems from a young age. Vision problems usually start by age 10 and lead to blindness.
• People with type II have moderate to severe hearing loss and normal balance. Vision problems start in the early teens and get worse more slowly than in type I.
• People with type III are born with normal hearing and near-normal balance but develop vision problems and then hearing loss.

There is no cure. Tools such as hearing aids or cochlear implants can help some people. Training such as Braille instruction, low-vision services, or auditory training can also help.

Usher syndrome is the most common condition that affects both hearing and vision; sometimes it also affects balance. The major symptoms of Usher syndrome are deafness or hearing loss and an eye disease called retinitis pigmentosa (RP) [re-tin-EYE-tis pig-men-TOE-sa].

Deafness or hearing loss in Usher syndrome is caused by abnormal development of hair cells (sound receptor cells) in the inner ear. Most children with Usher syndrome are born with moderate to profound hearing loss, depending on the type. Less commonly, hearing loss from Usher syndrome appears during adolescence or later. Usher syndrome can also cause severe balance problems due to abnormal development of the vestibular hair cells, sensory cells that detect gravity and head movement.RP initially causes night-blindness and a loss of peripheral (side) vision through the progressive degeneration of cells in the retina. The retina is the light-sensitive tissue at the back of the eye and is crucial for vision. As RP progresses, the field of vision narrows until only central vision remains, a condition called tunnel vision. Cysts in the macula [MAC-u-la] (the central part of the retina) and cataracts (clouding of the lens) can sometimes cause an early decline in central vision in people with Usher syndrome.

Usher syndrome affects approximately 4 to 17 per 100,000 people, and accounts for about 50 percent of all hereditary deaf-blindness cases. The condition is thought to account for 3 to 6 percent of all children who are deaf, and another 3 to 6 percent of children who are hard-of-hearing.

Usher syndrome is considered to be a ciliopathy. Although the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins results in a wide variety of symptoms including retinal degeneration (retinitis pigmentosa). Retinal degeneration associated with Usher syndrome is considered to be a retinal ciliopathy. Understanding that this condition is a ciliopathy may help the ophthalmologist to recognize associations between seemingly unrelated symptoms or diseases and keep a better eye out for other findings that may be present.

Usher syndrome is inherited, which means that it is passed from parents to a child through genes. Each person inherits two copies of a gene, one from each parent. Sometimes genes are altered, or mutated. Mutated genes may cause cells to develop or act abnormally.

Usher syndrome is inherited as an autosomal recessive disorder. “Autosomal” means that men and women are equally likely to have the disorder and equally likely to pass it on to a child of either sex. “Recessive” means that the condition occurs only when a child inherits two copies of the same faulty gene, one from each parent. A person with one abnormal Usher gene does not have the disorder but is a carrier who has a 50 percent chance of passing on the abnormal gene to each child. When two carriers with the same mutated Usher syndrome gene have a child together, each birth has a:

• One-in-four chance of having a child who neither has Usher syndrome nor is a carrier.
• Two-in-four chance of having a child who is an unaffected carrier.
• One-in-four chance of having a child who has Usher syndrome.

Usher syndrome is an inherited disorder with different subtypes caused by mutations in any of a number of genes:

Type I is divided in the following subtypes:

• IB, caused by mutations in the MYO7A gene (the most common one)
• IC, caused by mutations in the USH1C gene
• ID, caused by mutations in the CDH23 gene
• ID-F, caused by mutations in the PCDH15 and CDH23 genes
• IF, caused by mutations in the PCDH15 gene
• IG, caused by mutations in the SANS gene
• IH, caused by mutations in the USH1H gene
• IJ, caused by mutations in the CIB2 gene
• IK, caused by mutations in the USH1K gene

Type II is divided in the following subtypes:

• IIA, caused by mutations in the USH2A gene
• IIC, caused by mutations in the ADGRV1 gene
• IID, caused by mutations in the WHRN gene
• IIC, GPR98/PDZD7, caused by mutations in the ADGRV1 (ADGRV1 is also known as GPR98) and PDZD7 genes

Type III is divided in the following subtypes:

• IIIA, caused by mutations in the CLRN1 gene
• IIIB, caused by mutations in the HARS gene

Many of the genes related to Usher syndrome give instructions to make proteins needed for normal hearing, balance, and vision. The signs and symptoms of Usher syndrome occur when these genes have mutations that impair how they function. In some cases, the exact role of the genes involved is unknown. In some cases no mutation is identified, and it is believed that other genes may be involved.

Usher syndrome is inherited in an autosomal recessive manner. This means that a person must have a disease-causing change (mutation) in both copies of the gene associated with the syndrome in each cell to have Usher syndrome. One mutated copy is typically inherited from each parent, who are each referred to as a carrier. Carriers of an autosomal recessive condition usually do not have any signs or symptoms.

When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to have the condition, a 50% (1 in 2) chance to be an unaffected carrier like each parent, and a 25% chance to not be a carrier AND not be affected.

There are three types of Usher syndrome. In the United States, types 1 and 2 are the most common. Together, they account for up to 95 percent of Usher syndrome cases.

Type 1: Children with type 1 Usher syndrome have profound hearing loss or deafness at birth and have severe balance problems. Many obtain little or no benefit from hearing aids but may be candidates for a cochlear implant—an electronic device that can provide a sense of sound to people with severe hearing loss or deafness. Parents should consult with their child’s doctor and other hearing health professionals early to determine communication options for their child. Intervention should begin promptly, when the brain is most receptive to learning language, whether spoken or signed.

Balance problems associated with type 1 Usher syndrome delay sitting up without support. Walking rarely occurs prior to 18 months. Vision problems with type 1 Usher syndrome usually begin before age 10, starting with difficulty seeing at night and progressing to severe vision loss over several decades.

Type 2: Children with type 2 Usher syndrome are born with moderate to severe hearing loss but normal balance. Although the severity of hearing loss varies, most children with type 2 Usher syndrome can communicate orally and benefit from hearing aids. RP is usually diagnosed during late adolescence in people with type 2 Usher syndrome.

Type 3: Children with type 3 Usher syndrome have normal hearing at birth. Most have normal to near-normal balance, but some develop balance problems with age. Decline in hearing and vision varies. Children with type 3 Usher syndrome often develop hearing loss by adolescence, requiring hearing aids by mid-to-late adulthood. Night blindness also usually begins during adolescence. Blind spots appear by the late teens to early twenties. Legal blindness often occurs by midlife.

Diagnosis of Usher syndrome involves pertinent questions regarding the person’s medical history and testing of hearing, balance, and vision. Early diagnosis is important, as it improves treatment success. An eye care specialist can use dilating drops to examine the retina for signs of RP. Visual field testing measures peripheral vision. An electroretinogram [e-lec-tro-RET-in-o-gram] measures the electrical response of the eye’s light-sensitive cells in the retina. Optical coherence tomography may be helpful to assess for macular cystic changes. Videonystagmography [vi-de-o-nigh-stag-MAH-gra-fee] measures involuntary eye movements that could signify a balance problem. Audiology testing determines hearing sensitivity at a range of frequencies.

Genetic testing may help in diagnosing Usher syndrome. So far, researchers have found nine genes that cause Usher syndrome. Genetic testing is available for all of them:

• Type 1 Usher syndrome: MY07A, USH1C, CDH23, PCHD15, USH1G
• Type 2 Usher syndrome: USH2A, GPR98, DFNB31
• Type 3 Usher syndrome: CLRN1

Presently, there is no cure for Usher syndrome. Treatment involves managing hearing, vision, and balance problems. Early diagnosis helps tailor educational programs that consider the severity of hearing and vision loss and a child’s age and ability. Treatment and communication services may include hearing aids, assistive listening devices, cochlear implants, auditory (hearing) training, and/or learning American Sign Language. Independent-living training may include orientation and mobility training for balance problems, Braille instruction, and low-vision services.

Vitamin A may slow the progression of RP, according to results from a long-term clinical trial supported by the National Eye Institute and the Foundation Fighting Blindness. Based on the study, adults with a common form of RP may benefit from a daily supplement of 15,000 IU (international units) of the palmitate form of vitamin A. Patients should discuss this treatment option with their health care provider before proceeding. Because people with type 1 Usher syndrome did not take part in the study, high-dose vitamin A is not recommended for these patients.

General precautions for vitamin A supplementation:

• Do not substitute vitamin A palmitate with a beta-carotene supplement.
• Do not take vitamin A supplements greater than the recommended dose of 15,000 IU or modify your diet to select foods with high levels of vitamin A.
• Pregnant women should not take high-dose vitamin A supplements due to the increased risk of birth defects. Women considering pregnancy should stop taking high-dose vitamin A supplements for six months before trying to conceive.

Researchers are trying to identify additional genes that cause Usher syndrome. Efforts will lead to improved genetic counseling and earlier diagnosis, and may eventually expand treatment options.

Scientists are also developing mouse models with characteristics similar to Usher syndrome. Research using mouse models will help determine the function of Usher genes and inform potential treatments.

Other areas of study include developing new methods for early identification of children with Usher syndrome, improving treatment strategies for children who use hearing aids or cochlear implants for hearing loss, and testing innovative intervention strategies to help slow or stop the progression of RP. Clinical researchers are also characterizing variability in balance among individuals with various types of Usher syndrome.