What is Usher syndrome?

Usher syndrome is a syndromic IRD that affects both hearing and vision. The symptoms of Usher syndrome consist of hearing loss (found at an early age), vision loss caused by a condition called retinitis pigmentosa (RP), and sometimes balance problems.

There are three different clinical types of Usher syndrome: Type 1, Type 2, and Type 3.

While people with IRDs do have a higher risk of developing hearing issues late in life than the general population, Usher syndrome is characterised by hearing loss early-on in life.

Symptoms of Usher syndrome

Usher syndrome impacts three major senses in the body:

Vision

People with Usher syndrome have a type of vision loss called retinitis pigmentosa (RP). In RP, the rod cells, that give night vision, are first to deteriorate, resulting in night blindness and low peripheral vision. The lack of peripheral vision can result in narrowing of a visual field, or ‘tunnel vision’. The cone cells, that give colour and central vision, are next to degrade. RP is a progressive condition, meaning that vison will gradually decrease over time.

Hearing

Hearing loss can be present at birth in children with Usher syndrome or hearing loss develops shortly after. The onset of hearing loss differs between different types of Usher syndrome. Of all people with congenital bilateral, sensorineural hearing loss, it is estimated that at least ten percent have Usher syndrome.

Balance

Balance is a result of coordinated sensory input from eyes, the vestibular organs in the inner ear and the sensory systems of the body, such as the skin, muscles and joints. The vestibular organs are dysfunctional in Usher syndrome and result in balance issues.

Onset and severity of symptoms

The first symptom of Usher syndrome to be noticed is deafness, often from birth, followed by early childhood vision loss due to RP. Usher syndrome can present in one of three broad clinical types, Usher syndrome type I, type II and type III. These classes are determined by the severity of hearing loss, the presence or absence of balance problems and the age of onset of symptoms.

Usher type I

Usher type I causes deafness from birth and early childhood signs of RP. While cochlear implants may be of use, this form of deafness may be so severe that hearing aids may not be of use and individuals with Usher type I may not develop intelligible speech. Balance is often affected in those with type I and can slow the development of sitting or walking in children.

Usher type II

Individuals with Usher type II have less severe early onset hearing loss than those with type I and so affected children will benefit from hearing aids and develop intelligible speech. RP tends to present at the later age of teenage years in those with Usher type II and balance problems are not usually found.

Usher type III

Usher type III is the rarest form. Hearing at birth is usually normal but is lost during late childhood and becomes worse over time, with most middle aged individuals with type III having profound hearing loss. RP begins to develop by teenage years and continues to progress. Balance problems are experienced by some people with type III.

Genetic basis of Usher syndrome

The prevalence of Usher syndrome varies from country to country, but it is a rare condition affecting approximately 1 in 10,000 people. Usher syndrome is a genetic disease that occurs when there are mutations (defects) in genes that are important for the function of both photoreceptors in the retina and hair cells in the cochlea, or inner ear.

Usher syndrome is always inherited as an autosomal recessive trait. “Autosomal” refers to the fact that it is not located on the X or Y chromosomes. Therefore, both males and females can have Usher syndrome and can pass the mutation on to the next generation. As it is recessive, both copies of the Usher-related gene inherited from both parents must be mutated. If just one copy of the gene is mutated, the person will not have symptoms but may pass the mutated gene onto their children. They are referred to as ‘carriers’. Patients with a combination of early-onset partial deafness and retinitis pigmentosa due to alterations in the mitochondrial DNA (a different type of DNA in cells) do not fall into the category of Usher syndrome.

If a family member is diagnosed with Usher syndrome, it is strongly advised that other members of the family also have an eye exam by an eye doctor (ophthalmologist) who is specially trained to detect retinal diseases. As the deafness becomes obvious at a much earlier age than the RP in patients with Usher syndrome, it is particularly important that younger siblings with a hearing problem have a careful eye examination.

While there are three clinical types: type 1, type 2 and type 3 (based on the severity and age when symptoms appear), researchers have found 11 different genes associated with these clinical subtypes. Usher type 1 currently has six different genes associated with it, Usher type 2 has three genes, and Usher type 3 has two genes. Genetic testing is the only reliable way of determining the true genetic type as it is impossible to determine this from clinical analysis. You can find more information on the genes of Usher syndrome here (LINK to Usher’s gene list).

A definitive diagnosis of Usher syndrome requires genetic testing. A genetic confirmation of Usher syndrome is also necessary for participation in in gene-based clinical trials such as gene therapy. Genetic results also can be used by researchers to learn more about different types of Usher syndrome and contribute to developing treatments. Unfortunately, only a small number of people in the Usher community have had genetic testing to date.

Some people are interested in genetic testing, but don’t know how to get started. Some want to know if their public health system or insurance will pay for their genetic testing, but don’t know how to find out. Some cannot afford genetic testing. See our section on genetic testing for more information about access to genetic testing http://www.retina-international.org/toolkit-redalert.

Coping with a Diagnosis

The time of diagnosis can be difficult, and many different emotions can arise. For some people, it may be quite distressing, upsetting or overwhelming. People often struggle to understand how this has happened and how they will cope now and in the future. If you feel like this, you are not alone. There is no need to feel guilty about these feelings. It is important to find support for your situation and to have a way to express your feelings and thoughts.

The initial feelings that people experience after a diagnosis can include shock, denial and despair. These feelings will lessen as time passes. While it is natural to feel like this after such a life-changing diagnosis, it could help you to talk to a healthcare professional or a counsellor. With the appropriate support and guidance, it is possible to work through and overcome difficulties to find new and life-enhancing meaning and purpose in living.

Some people with sight loss can experience visual hallucinations or see things that are not there. This can be very frightening for people and some fear that they are having mental health problems. However, it is a common condition in people who have recently lost their sight where the brain is adjusting to the loss of visual information. It is called Charles Bonnet syndrome and while it can be distressing, the hallucinations can get less frequent as time passes.

For Parents

If your child has been diagnosed with Usher syndrome, it is important to remember that, despite the diagnosis, your child has not changed. Your child is a person that is much more than the threat of blindness. Children are more aware of things than we give them credit for, and so it is important to be honest and answer their questions truthfully and compassionately. Ideally, a child should be told about their diagnosis in an age-appropriate way by a loving person who is close to them. If a child isn’t told about their diagnosis but then discovers information from sources other than the family, for example overhearing a doctor’s conversation, over time this can foster mistrust and resentment.

There are many supports and outside help available to parents, so that they don’t have to do everything alone. Parents can often feel that they must be the sole doctor and carer and nurse for their child. However, this can be an overwhelming and impossible task. Outside help can support those roles to allow parents to do the very important role of being parents to their child. Please see the member charities of Retina International for a local charity near you http://www.retina-international.org/our-members.

It can be difficult to explain the complexities of vision and vision loss to children. However, there are useful videos designed to introduce children to some of the concepts. Some of these are listed here:

The Visual System: How Your Eyes Work

Ask a Scientist: Eyes at Night

Ask a Scientist: Eye Myths and Facts

Children with Usher syndrome begin to develop night blindness in dimly lit areas and the progression of ‘tunnel vision’ means that that their ability to see to the sides, above and below is be impaired. As long as the lighting is good, vision for reading and fine detail can be functional into adulthood. Quick changes in light levels and glare may require loner adjustment times for people with RP.

Children with other forms of hearing loss may not have balance or mobility issues, but such issues are common in those with Usher syndrome due to vestibular problems. As vision declines, balance issues can increase, especially in dim light. Depth perception may be also affected. Sometimes such mobility issues are not apparent until after an accident has occurred. To ensure safe travel, orientation and mobility instructors can provide appropriate training. Some activities such as riding a bicycle or hiking a steep hill may require different skills and awareness, and so appropriate planning by parents or caregivers can be beneficial to enable children with Usher syndrome to participate in fun activities.

An early confirmed diagnosis of Usher syndrome can be very beneficial when planning educational supports for a child. As a child with hearing loss will learn in a different way to a child with both hearing and vision loss, early diagnosis of Usher can ensure appropriate supports are in place before issues with vision arise. Vision rehabilitation is one of the supports that ensure you have the right information, training, skills and aids to live well with sight loss. Your local sight loss charity will have information on local supports http://www.retina-international.org/our-members.

Simple adjustments such as reviewing the lighting in your home can make helpful improvements. A low vision service can advise you on the use of aids such as magnifiers and specialist lighting. Vision rehabilitation support is not just for physical adjustments but also takes into account a person’s communication needs, how they keep in touch with others and what will enable them to access education. This can be aided with help with reading, writing, talking books and newspapers, telling the time, using technology such as smartphones, tablets and speech software. Most smartphones or computers have accessible features built in while there are many packages available that enable everyone to use a computer. ViaOpta is a recently developed suite of mobile applications to assist visually impaired people with their daily lives. These apps allow individuals to maintain their independence by assisting with daily activities, navigating their local region and recognising people and places using image analysis technology. See https://www.viaopta-apps.com for more details.

Visual and hearing impairments do not preclude an individual from education or employment. Appropriate rehabilitation can ensure access to training, education and learning opportunities as well as advice about disability employment.

A genetic diagnosis of Usher syndrome is also helpful to parents for planning their family. As Usher syndrome is an autosomal recessive genetic condition, both parents must be carriers for a child to have Usher syndrome. When both parents are carriers, each child has a 25% chance of developing Usher syndrome, a 50% chance of being a carrier and 25% chance of not inheriting any Usher-related mutation. For more information on genetic testing, please see out Red Alert toolkit http://www.retina-international.org/toolkit-redalert.

Daily life with Usher syndrome

The Usher Syndrome Coalition is a wonderful initiative that has developed a series of educational videos about Usher syndrome in American Sign Language (ASL) and has kindly given Retina International permission to share these videos here.

The videos include topics such as research and new interventions, as well as daily living with Usher syndrome as a parent and as a child. If you have questions about the videos, please contact the Usher Syndrome Coalition at info@usher-syndrome.org.

VIDEO TRANSCRIPTS AND DESCRIPTIONS

Kevin Richmond kicks off this series on Usher syndrome in ASL by summarizing the history of the Usher Syndrome Coalition and our goal.

 

Kevin provides a brief description of Usher syndrome, the most common genetic cause of combined deafness and blindness.

 

This video provides an overview of the vision loss related to Usher syndrome: retinitis pigmentosa.

 

A brief description of the Usher syndrome type 1 in ASL with English captions.

 

A brief description of the Usher syndrome type 2 in ASL with English captions.

 

This video provides an overview of Usher type 3 in ASL with English captions.

 

Just because a person is deaf and has poor vision doesn’t mean that they have Usher syndrome. How can you find out for sure if you have Usher syndrome?

 

How is Usher syndrome inherited? Kevin explains the basics of how the Usher gene is passed down in families.

 

Kevin explains the USH Trust registry and why it’s so important to the Usher community. Individuals may register at www,usher-registry.org

 

For 10 days, Kevin has been teaching us about Usher syndrome. Now, he shares his own story as a person living with Usher syndrome.

 

Kevin explains the difference between these 2 commonly used words in the research world.

 

What is the process of research, from theory to treatment?

 

We usually think of viruses as making us sick. Kevin explains how researchers are testing the use of viruses to deliver healthy genes to the eye.

 

Kevin shares his personal opinion about how his identity might be influenced by treatments or a cure. Fascinating food for thought!

 

Researchers have used stem cells from donors to treat diseases. Now, they can create these cells from your own tissue, reducing the risk of rejection. Kevin explains how this process is being tested to repair retinal cells.

 

Kevin talks about the K-12 years and offers some ideas about supports for students with Usher syndrome.

 

College provides an opportunity for young adults to learn about the Vocational Rehabilitation system and how to advocate themselves.

 

Do adults with Usher syndrome work (of course) and what types of jobs do they have? Kevin talks about life in the real world.

 

Kevin has talked about life with Usher syndrome at various milestone ages. But what does the Usher community look like as a whole?

 

The diversity of the Usher community applies to communication too. Kevin describes some of the many ways that individuals with Usher syndrome communicate. What’s your preference?

 

Kevin provides an overview of the NDBEDP, or National Deaf-Blind Equipment Distribution Program, also known as iCanConnect.

 

Kevin shares some fun facts about Usher syndrome.

 

Kevin attended his first USH Connections Conference in 2017. If not for that conference, these videos would probably not exist. Read about his experience at the conference.

 

A brief summary of resources available through the Usher Syndrome Coalition.

 

Kevin takes a look at the past 25 days of ASL videos. What an amazing journey!

Where Are We Now?

Current treatments for Usher syndrome focus on helping an individual to adapt to hearing and vision loss and to maximising the vision and hearing that they do have. This includes the use of hearing aids, assistive listening devices, cochlear implants, mobility training, and low vision services. The wide range of assistive technologies available provides plenty of choice for users at all stages of sight and hearing loss and this technology has also removed many barriers to education and employment. Please see our section on Coping with a diagnosis for more information on how to live well with Usher syndrome.

Despite the lack of current treatments for Usher syndrome, general eye check-ups are important. This is because people with Usher syndrome are still at risk for other kinds of eye problems that can affect the general population, such as cataracts, and may be treatable. Regular visits to your eye doctor can also make you aware of current advances as we learn more about these conditions.

Researchers and companies are working towards interventions that may one day be a cure. There may be more trials for Usher syndrome in future, in the next section ‘Where are we going?’ we describe the potential interventions undergoing trials. You can find out more information on current clinical trials by searching on www.ClinicalTrials.gov and with our list of IRD-related clinical trials here (LINK TO PDF).

Where Are We Going?

Prospects for the development of effective Usher syndrome treatments have never been brighter. The syndrome is passed down through a recessive pattern of inheritance with only one pair of genes affected and is therefore a prime candidate for gene therapy. Gene therapy involves using harmless viruses to deliver and insert a healthy copy of the gene into the retina, thereby restoring function. This approach has led to exciting initial results in a number of other retinal diseases. Usher syndrome gene therapy is quite challenging as the genes affected tend to be extremely large in size and difficult to deliver. However, scientists are exploring other harmless viruses that have the ability to safely deliver these large genes. One trial is currently in the early stages of recruitment in the USA and France, and more trials are planned in the future.

Some forms of Usher syndrome are due to mutations known as “nonsense” mutations that lead to the incomplete and premature production of essential proteins. There are now new drugs in the very early stages of testing for a number of other rare genetic conditions due to nonsense gene mutations that may have the potential to stop the defective protein synthesis and produce the correct form of the protein. Neuroprotective agents that aim to preserve the function of the rod and cone photoreceptor cells for longer also hold huge potential for Usher syndrome, by maintaining a small, but significant amount of central vision.

Many of the therapies that are in development will not bring back the lost vision that occurs due to Usher syndrome, but they do have the potential to slow down or halt further degeneration, until other therapies, such as the exciting developments that have occurred in stem cell research, become available. Efforts at transplanting stem cell derived photoreceptor cells are still at an early stage of research, however a number of recent animal studies have shown the potential to restore function in the eye, which may pave the way for human studies in the future. Information about clinical trials that are currently being conducted worldwide can be found on www.ClinicalTrials.gov and can be searched by condition and trial location.

As can be seen from the recently approved gene therapy for biallelic REP65 LCA, Luxturna, many of these new treatments have a high price and are deemed to be very expensive. Therefore, while action is needed to maintain momentum in research and clinical trials to find these treatments, it is also of great importance to advocate for access to these treatments for all. Please see our Advocacy section for helpful information.

Access to Treatments

Access to treatments is a universal issue, with the reportedly high prices of many new treatments being a potential barrier globally. While treatments using new technologies such as gene therapy may have a high price tag at first look, the fact remains that some could result in a once-off treatment that will potentially prevent vision loss for at least 10 years, if not for life. It is of utmost importance, therefore, that patient groups in every country have the right information and the right advocacy tools to ensure that such life-changing treatments are made available in their countries.

Information that would help illuminate the benefits of such a treatment includes:

  • the number of potential patients in each country, which requires access to genetic diagnosis. Please see our Red Alert Toolkit for more information http://www.retina-international.org/toolkit-redalert
  • the impact of these conditions on the life of the patients and of their families
  • the impact of these conditions on society, including the everyday care needs of someone with visual impairment from young children to adults; the potential effect on the education and employment of the patient and their carers; the additional supports supplied by health care providers, health systems or charity groups.

Retina International see the need for such information to be gathered and we are actively engaged in projects to this end. If you would like to contribute information of this kind, we would love to hear from you. Please get in touch info@retina-international.org. and you can visit our section on Advocacy for more information on the need for data on impact.

While treatments such as gene replacement therapy are revolutionary, they are still quite a way from being universally available for all types of LCA. While we await new treatments, individuals with LCA and other IRDs can access appropriate visual supports to ensure they can live as fully and as independently as possible. Please see our sections on Coping with a diagnosis and Life with Usher syndrome for more information.