Usher Syndrome

Description

Usher Syndrome refers to a group of inherited retinal degenerations that have both hearing loss and progressive deterioration in vision due to Retinitis Pigmentosa (RP). Three main clinical types of Usher Syndrome have been characterised; Type 1, Type 2 and Type 3.

The vision loss which presents as part of Usher Syndrome is due to a form of RP which causes the death of the light sensitive cone and rod photoreceptor cells, responsible for capturing images from the visual field. While patients with RP have a greater tendency to develop hearing difficulties as they age compared to the general population, the term Usher Syndrome is reserved for patients where the hearing loss becomes obvious at a very early age.

The prevalence of Usher Syndrome varies from country to country, but it is thought to affect approximately one in 10,000 people. Usher Syndrome represents half of all people with combined deafness and blindness and in some studies, accounts for up to 18% of all cases of RP. The rate of progression of vision loss can vary widely from person to person and even within members of the same family.

Symptoms

There can be a variable presentation and age range at which symptoms of Usher Syndrome occur and this depends on what type of Usher Syndrome a person has (Type 1, Type 2 or Type 3). Deafness or loss of hearing is one of the major symptoms and is the first symptom experienced by those with Type 1 or Type 2 Usher Syndrome. Vision loss will also occur, with night and low light vision the first to be affected, followed by a loss of peripheral (side vision). In some cases, vision may be further impacted by the development of cataracts, a clouding of the natural lens within our eyes. This vision loss progresses to affect central vision and eventually leads to blindness.

In Ireland, Types 1 and 2 are the most common forms of Usher Syndrome.

Individuals with Usher Type 1 develop profound deafness in both ears from birth. The deafness is generally so early in onset and so severe that hearing aids may not be of value, (although cochlear implants may be beneficial), and patients fail to develop intelligible speech. In early childhood, individuals also present with symptoms of RP. Vision loss presents during childhood and may also be accompanied by problems with balance. For example, some children may learn to sit independently or walk a little later than would be expected.

Balance symptoms may be aggravated by the constriction of visual field that develops as the visual symptoms of Usher Syndrome progress.

Individuals with Usher Type 2 have an early onset hearing loss. The deafness is slowly progressive, but less severe than in Type 1 and the child will benefit from hearing aids and can develop intelligible speech. The features of RP usually become obvious during teenage years, with vision loss demonstrating a much slower rate of progression than in Type 1. Individuals with Type 2 Usher Syndrome do not encounter difficulties with balance.

Usher Type 3 is a very rare form of Usher Syndrome and is generally found in people who have family origins in Finland or are Ashkenazi Jewish. Hearing loss has a later onset in Type 3, presenting between the second and fourth decades of life and becomes more severe over time. Vision loss due to RP occurs late in childhood or in adolescence and is also progressive.

Causes

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.

So far, researchers have found at least 11 genes that are associated with the three main types of the syndrome. MYO7A is the most common gene mutation associated with Usher Syndrome Type 1, with USH2A the most common mutation for Type 2 and CLRN1 the most common for Type 3. Usher Syndrome is inherited in a recessive pattern, meaning both copies of a gene don’t work correctly. This means that the individual’s mother and father have both passed on a mutation in a gene causing Usher Syndrome to their child.

More rarely, cases of digenic inheritance have been reported. This means that mutations in at least two genes give rise to the condition in an individual.

Patients with a combination of early-onset partial deafness and retinitis pigmentosa due to alterations in the mitochondrial DNA do not fall into the category of Usher Syndrome.

More information about genetic inheritance patterns can be found at out Genetic Inheritance.

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 can become 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.

Diagnosis

Usher Syndrome is diagnosed through a number of assessments which help with providing the correct diagnosis.

The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual acuity and the visual field.

An individual may receive a number of imaging tests. Information about the condition may be identified using colour or wide-field fundus photography (which essentially takes photos of the back of the eye). Fundus autofluorescence may be used to identify stress or damage to the retinal pigment epithelium. Optical coherence tomography (OCT) can also be used to assess the various layers at the back of the eye.

An individual may also have an electroretinogram (known as an ERG), which is used to evaluate the functioning of the different types of photoreceptor cells (rods and cones) and to assess for progression.

A genetic test is also an important component of testing, to ensure the correct condition is diagnosed. For people living in Ireland, genetic testing for Usher Syndrome can be performed through the Target 5000 programme.

For further information, please contact the Research Department on 01 6789004.

Genetic Diagnosis

It’s often impossible to tell which type of retinal disease a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis.

The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including Usher Syndrome. Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition.

As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

There are no proven treatments for the visual effects Usher Syndrome as of yet, although recent years have noted advances in clinical research and development. To find out more about advances made in this area, please visit the ‘Latest Research’ section.

Maximising an individual’s quality of life focuses 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.

General eye check-ups are important for people living with Usher Syndrome, as these individuals may still be at risk of developing other kinds of eye problems that can affect the general population, some of which may be treatable.

No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health.

For further information, please contact the Research Department on 01 6789004.

Research

Advances in research have yielded a greer of other retinal diseases. Developing therapies for Usher Syndrome is quite challenging as the genes affected tend to be extremely large in size and difficult to deliver. However, scientists are exploring other safe viruses that have the ability to safely deliver these large genes into the cells at the back of the eye. One clinical trial is currently underway in the USA and France, which aims to target the MYO7A gene, the most common gene associated with Type 1 Usher Syndrome.

Neuroprotective agents that aim to preserve the function of the rod and cone photoreceptor cells for longer also hold huge potential for Usher Syndrome. Ciliary neurotrophic factor is a factor which is thought to demonstrate potential in protecting the light sensitive photoreceptors of the retina and is currently being investigated in an early-phase clinical trial for Usher Syndrome Types 2 and 3.

A relatively new area of focus is in the treatment of Usher Syndrome using antisense oligonucleotides. These are molecules which can alter RNA, the exact copy of your DNA, which provides the template for protein production. In the eye, proteins can play essential roles, including in eye structure and function. Where a person has a genetic mutation in their DNA, this will also be present in their RNA (as it is an exact copy) – leading to the generation of an incorrect or damaged protein.

Antisense oligonucleotides can skip the mutation in the RNA and either reduce, restore or modify the generation of the protein. Using these agents should bring benefit to the condition. A new clinical trial has commenced, with the intervention aiming to target the USH2A gene and skip a region of the RNA known as “Exon13” in Usher Type 2. Researchers hope that this will lead to a more functional gene and therefore protein being produced, which could positively impact the condition. This clinical trial is in its early stage with work ongoing.

Information about clinical trials can be found on their website and can be searched by condition and trial location.

Fighting Blindness currently support a number of research initiatives which aim to improve the diagnosis, care and quality of life of individuals living with Usher Syndrome.

Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with Usher Syndrome.

Support

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Usher Syndrome.

Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496.

A mindfulness group is also available on every Wednesday at the Fighting Blindness office at 11am.

For technology support and guidance, the Dublin-based Technology Exchange Club meets every Monday at the Fighting Blindness office at 11am. Another Technology Exchange Club, based in Cork, meet every Saturday in the Cork City Library, Grand Parade, Cork City at 11am. The Cork-based club do not meet on Bank Holiday weekends or on the second Saturday of the month. For further information please contact insight@fightingblindness.ie or call 01 6746496.

Resources

Féach provides support for parents of children living with sight loss in Ireland.

ChildVision is the national education centre for children with sight loss in Ireland.

NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland.

Irish Guide Dogs for the blind helps individuals and their families to achieve improved mobility and independence.

Deafblind Ireland is an important resource for people living with hearing and sight loss, their families and professionals who work with them. They also provide services to ensure that those living with hearing and sight loss are fully supported and able to live an independent life.

Chime provides many supports for those living with hearing loss.

The Anne Sullivan Foundation provides advice, information and services for people living with hearing and sight loss. They also provide a range of activities and individualised programmes.

Irish Deaf Society provides support for Irish sign-language and offer courses for people with hearing loss.

Retina International provides useful information on Usher Syndrome.

Usher Syndrome Coalition provides information and supports research for Usher Syndrome.

Sense provides information and advice, services, support and activities for people who are deafblind.

CUREUsher is a charity dedicated to raising funds to increase collaboration and research into a cure for Usher syndrome and to empower those living with the genetically inherited disease.

Last Updated: 4th February 2019