What is Usher Syndrome?
USHER SYNDROME IS THE MOST COMMON GENETIC CAUSE OF COMBINED DEAFNESS AND BLINDNESS.
- Usher Syndrome
- Hallgren syndrome
- Usher-Hallgren syndrome
- Retinitis pigmentosa-deafness syndrome
- Retinitis pigmentosa-dysacusis syndrome
- Dystrophia retinae dysacusis syndrome
- Deafness-retinitis pigmentosa syndrome
- Dystrophia retinae pigmentosa-dysostosis syndrome
- Graefe-Usher syndrome
Vision: Vision loss in Usher syndrome is caused by a progressive vision disorder known as retinitis pigmentosa (RP). RP causes the light-sensing cells in the retina to gradually deteriorate, initially resulting in night blindness, followed by a narrowing of the visual field, commonly known as tunnel vision.
Hearing: Children with Usher syndrome are born with or develop hearing loss. It’s estimated that upward of 10 percent of individuals with congenital bilateral, sensorineural hearing loss have Usher syndrome.
Balance: Balance is achieved and maintained through input from your eyes, the vestibular organs in the inner ear and the sensory systems of the body, such as the skin, muscles and joints. Thus, people with Usher syndrome suffer from severe balance issues due to vestibular dysfunction.
There are three clinical types: type 1, type 2 and type 3, which are distinguished by the severity and age when the signs and symptoms appear. There are at least eleven different genetic types of Usher syndrome, as determined by the genes that are involved. There are six different genes that cause Usher type 1, three that cause Usher type 2, and two that cause Usher type 3. One cannot determine the genetic type by clinical testing; DNA testing is the only reliable way of determining the true genetic type.
Type 1 – causes profound deafness, Vision loss cause by retinitis pigmentosa (RP) may be noticed before the age of 10. Poor balance from birth is often associated with Usher type 1, which causes delays in sitting and walking. Children with Usher type 1 who receive cochlear implants at an early age usually communicate using speech and lip-reading. Many adults with Usher 1 communicate with sign language and identify as a culturally Deaf and/or DeafBlind.
Type 2 – causes a moderate hearing loss. RP may not become apparent until adolescence. Speech assisted by the use of lip-reading and hearing aids or cochlear implants will usually be their primary method of communication. Balance is not affected, therefore children with type 2 walk at the typical age of 10 to 14 months.
Type 3 – is the rarest form of Usher syndrome. It occurs with higher frequency in individuals of Ashkenazi Jewish and Finnish heritage. Children usually have normal hearing and vision at birth, then develop hearing loss and RP in adolescence or later. Hearing can deteriorate steadily over ten or fifteen years. Some with type 3 also experience balance problems.
There are at least eleven different genetic types of Usher syndrome. There are six different genes that cause Usher type 1, three that cause Usher type 2, and two that cause Usher type 3. DNA testing – usually with a simple blood test – is the only reliable way of determining the true genetic type.
Recent breakthroughs in genetic testing are allowing for earlier diagnosis of all types of Usher syndrome
Usher Type 1
Usher syndrome type 1 is a recessive genetic disease. This means that a child receives two copies of the same Usher 1 gene, one from each parent.
Children with Usher type 1 are usually born profoundly deaf and experience progressive vision loss due to a retinal disease called retinitis pigmentosa (RP). The symptoms of RP first manifest as difficulty seeing in dimly lit areas – or night blindness – and a gradual loss of peripheral vision (tunnel vision). These symptoms will generally be noticed before the age of 10 and continue through adulthood.
Children and adults with Usher type 1 usually have vestibular issues which affects balance. Balance issues manifest early in children with Usher type 1, and they often learn to sit up and walk later than their peers. Balance problems can become more pronounced as visual fields decrease.
Today, Usher syndrome is usually diagnosed before adulthood, but many older people report that the diagnosis wasn’t made until later in life when the vision loss from RP became severe enough to interfere with their mobility. Genetic testing – usually through a simple blood test – is the only way to definitively diagnose Usher syndrome.
Carriers of Usher Type 1
Usher syndrome occurs when an individual inherits two copies of the same type of Usher 1 gene – one from each parent. If an individual has one Usher type I gene and one gene that is not Usher, they are considered to be a “carrier” of the Usher gene. Carriers have typical vision, hearing and balance. If two carriers of the same gene have a child, there is a 25% chance in each pregnancy that their child will inherit two Usher genes – one from each parent – and that child will have Usher syndrome. If a child inherits one Usher 1 gene and one non-Usher 1 gene, that child will be a carrier, like their parents. He or she will have typical vision, hearing and balance. It is also possible that a child of 2 carriers will inherit 2 non-Usher syndrome genes, which means that they will not have Usher syndrome and they will not be a carrier.
Hearing in Type 1
Hearing loss in children with Usher syndrome type 1 is usually severe to profound and present at birth.
Vision in Type 1
A person with Usher 1 may become legally blind as a young adult primarily because of severe tunnel vision. Central vision is usually retained into adulthood, allowing individuals to continue to read print and use a computer. Some adults with Usher 1 will lose central vision more quickly, retaining only light perception.
Balance in Type 1
Individuals with Usher type 1 often have limited vestibular functionality. This can result in severe balance issues. Children with Usher type I are often late sitters or late walkers. It is not uncommon for children with type I Usher to begin walking at 24-36 months. These balance issues are present throughout life and often become more pronounced in low light or as the vision degrades.
Physical and occupational therapy can help individuals with type I with their balance issues. Core strengthening and hippotherapy can improve a person’s ability to compensate for the decreased vestibular functionality. Mobility training can also be also helpful.
Genes involved in Type 1
Usher syndrome type I is the most severe form of Usher syndrome and is characterized by congenital, profound, sensorineural hearing loss; vestibular dysfunction, often manifested as delayed walking (>18 months); and the onset of RP by the age of ten (Keats and Lentz, 2006). Usher syndrome type I is further subdivided into 5 types. Mutations in the MYO7A, USH1C, CDH23, PCDH15, and USH1G (SANS) genes cause Usher syndrome type 1B, type 1C, type 1D, type 1F and type 1G respectively.
Mutations in these genes account for most cases of Usher syndrome Type I. Mutations in MYO7A are the most common accounting for 39-55% of cases (Keats and Lentz, 2006). An Ashkenazi Jewish founder mutation, R245X, has been identified the PCDH15 gene which has a carrier frequency of up to 2.5% in this population. MYO7A, USH1C, CDH23, and PCDH15 mutations have also been reported in several families with recessive nonsyndromic hearing loss. In addition, a few families with autosomal dominant nonsyndromic hearing loss (DFNA11) have also been described with mutations in MYO7A.
Although these are the most common characteristics of Usher syndrome due to mutations in these genes, there can be variations. Overlapping and atypical presentations have been described for all three types of Usher syndrome. For example some individuals with mutations in type I genes may have a milder presentation (moderate hearing loss and/or a normal vestibular system). In addition, certain genes (MYO7A, USH1C, CDH23, PCDH15, and DFNB31) can cause isolated hearing loss without developing retinitis pigmentosa.
Identified disease causing mutations in all of these genes include missense, nonsense, frameshift, splice-site as well as deletions distributed across nearly all exons.
Usher Type 1 subtypes
Although all individuals with Usher type 1 demonstrate similar symptoms, the genetic causes differ. Some are more common than others. Usher subtype 1b is by far the most common form of Usher type 1 and accounts for over 40% of all cases. Subtype 1d appears to be next most common and is responsible for about 25% of all cases. Usher Ic is not very common in the general USA population, but it is common among French Acadians in Louisiana. Usher 1f and 1g are uncommon and so far only a few cases have been reported. There is a form of Usher 1f that is common among people with Ashkenazi Jewish ancestry. Usher 1a does not exist and 1e is quite rare. There is evidence that there are more Usher 1 subtypes that have not yet been identified.
Usher Type 2
Individuals with Usher type 2 are born hard-of-hearing and gradually lose their vision due to retinitis pigmentosa (also known as RP). Hearing tests show a sloping hearing loss that is mild to moderate in the low frequencies and severe to profound in the high frequencies. Vestibular problems are absent in type 2, which distinguishes it from type I. RP generally manifests in the teen years and progresses throughout life.
Today, most diagnoses are made before adulthood, but older people still report that the diagnosis wasn’t made until later in life when the RP became severe enough to interfere with their mobility.
Carriers of Usher Type 2
When an individual has one Usher 2 gene (carrier), half the normal amount of the protein usherin is produced. Scientists believe that this is sufficient for normal vision and hearing, therefore no observable symptoms result. There are theoretical reasons to think that there may be very mild hearing and vision problems in older adults who are carriers, but this has never been studied. It may be that these genes are partly responsible for some of the hearing and vision losses that all of us have as we grow older.
Hearing in Type 2
People with Usher type 2 are born with a moderate to severe hearing loss. The hearing loss is milder in the low frequencies and more severe in the higher one. Since most speech involves the lower frequencies, this means that adults and children with Usher type 2 will usually have good oral communication skills.
Vision in Type 2
A person with Usher 2 may become legally blind as a young adult primarily because of severe tunnel vision. While most adults retain good central vision for most of their lives, some with Usher 2 will lose their functional vision as they age.
Balance in Type 2
Individuals with Usher type 2 rarely experience balance issues.
Genes involved in Type 2
There are three subtypes of type 2 which have known gene locations: USH2A, GPR98 (VLGR1)and DFNB31 (WHRN).
USH2A accounts for approximately 80%, GPR98 (VLGR1) accounts for approximately 15%, and DFNB31 accounts for approximately 5% of type 2 cases. DFNB31 mutations have also been reported in several families with recessive nonsyndromic hearing loss. Identified disease-causing mutations in all of these genes include missense, nonsense, frameshift, splice-site as well as deletions distributed across nearly all exons.
Some mutations in USH2A can cause retinitis pigmentosa without hearing loss.
Usher Type 2 subtypes
Subtype 2c appears to be uncommon. Because the genes for 2b and 2d have not been identified, we don’t have any idea about their frequencies, but we believe them to be uncommon. There is evidence that there are more Usher 2 subtypes that have not been recognized.
Usher Type 3
Usher syndrome type 3 is is the rarest form of Usher syndrome, characterized by later onset hearing loss, RP that manifests between the second and fourth decades of life and variable vestibular dysfunction. Forty-two percent of those with Usher syndrome in Finland are thought to have USH3. It is also found in individuals of Ashkenazi Jewish heritage.
Hearing in Type 3
Individuals are born with normal hearing. Hearing loss begins during lat childhood or adolescence and progresses to profound hearing loss.
Vision in Type 3
Children born with Usher type 3 have retinitis pigmentosa (RP) that manifests in later childhood or early adolescence.
Vestibular Function in Type 3
Vestibular (balance) function is typical at birth and may become affected in some with Usher 3 in adult years.
Genes involved in Type 3
To date, only mutations in the CLRN1 (USH3A) and HARS (USH3B) genes are known to cause this type of Usher syndrome. Identified disease causing mutations in these genes include missense, nonsense, frameshift, splice-site as well as deletions distributed across nearly all exons.
Usher syndrome is a variable condition; the degree of severity is not tightly linked to whether it is Usher 1, 2 or 3. For example, someone with Type 3 may be unaffected in childhood but go on to develop a profound hearing loss and a very significant loss of sight by early to mid-adulthood. Similarly, someone with Type 1, who is therefore profoundly deaf from birth, may keep good central vision until the sixth decade of life, or even beyond. People with Type 3, who have useful hearing with a hearing aid, can experience a wide range of severity of the RP. Some may maintain good reading vision into their sixties, while others cannot see to read while still in their forties.
Usher syndrome I and II are associated with a mutation in any one of six or three different genes, respectively, whereas only one mutation has been linked with Usher III. Since Usher syndrome is inherited in an autosomal recessive pattern, both males and females are equally likely to inherit Usher syndrome.Consanguinity of the parents is a risk factor. Children of parents who both are carriers of the same mutation have a one fourth chance of inheriting the condition and children of such parents who are unaffected have a two thirds chance of being carriers. Children of parents where only one parent is a carrier have a no chance of having the disease but have a one half chance of being a carrier. First recognized in the 19th century, Usher syndrome was the first condition to demonstrate thatphenotypes could be inherited in tandem; deafness and blindness are inherited together, but not separately. Animal models of this human disease (such asknockout mice and zebrafish) have been developed recently to study the effects of these gene mutations and to test potential cures for Usher syndrome.
Other interesting articles and links
• Usher Syndrome – Symptoms and Causes of Usher Syndrome
• Usher Syndrome . Psychology Wiki
• Usher Syndrome Type II – U.S. National Library of Medicine – National Institutes of Health
• Usher Syndrome Type I – U.S. National Library of Medicine – National Institutes of Health
• What is Usher syndrome?
How common is Usher syndrome?
Where can I find additional information about Usher syndrome?
Inheritance of Usher Syndrome
Mutations in the CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, and USH2A genes cause Usher syndrome.
The genes related to Usher syndrome provide instructions for making proteins that play important roles in normal hearing, balance, and vision. They function in the development and maintenance of hair cells, which are sensory cells in the inner ear that help transmit sound and motion signals to the brain. In the retina, these genes are also involved in determining the structure and function of light-sensing cells called rods and cones. In some cases, the exact role of these genes in hearing and vision is unknown. Most of the mutations responsible for Usher syndrome lead to a loss of hair cells in the inner ear and a gradual loss of rods and cones in the retina. Degeneration of these sensory cells causes hearing loss, balance problems, and vision loss characteristic of this condition.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Usually the disease is inherited from both parents who are symptom-free genetic carriers of Usher Syndrome.
Inheritance from one diseased parent odds: Usually 0% chance of disease, 100% chance of being a genetic carrier if one parent has an autosomal recessive disease (not just carrier).
Inheritance from two carrier parents odds: 25% disease, 50% chance carrier, 25% neither for autosomal recessive diseases.
Gender bias in inheritance: Male or females get the disease equally.
Other interesting articles
UNRAVELING USH: PROGRESS IN RESEARCH TO TREAT USHER SYNDROME
Here you will find summaries of the treatment approaches and research progress for all subtypes of Usher syndrome.
• Safety Study in Retinal Transplantation for Retinitis Pigmentosa.
The long-term goal is to show that retinal transplantation can help to prevent blindness and to restore eyesight in patients with the inherited disease retinitis pigmentosa.
• Trials for ‘bionic’ eye implants
bionic eye implant that could help restore the sight of millions of blind people could be available to patients within two years.
• The IOL-Vip System: a double intraocular lens implant for visual rehabilitation of patients with macular disease.
Orzalesi N, Pierrottet CO, Zenoni S, Savaresi C.
University Eye Clinic, San Paolo Hospital, Milan, Italy
• IOL-VIP system: new hope for low vision patients
By: Professor Giuseppe Ravalico
Ophthalmology Times Europe
• Optobionics’ Artificial Silicon Retina™ microchip (ASR™)
invented by Dr. Alan Chow and his brother Vincent Chow. Dr. Chow is an ophthalmic surgeon and assistant professor and his brother Vincent is an electrical engineer. The ASR was designed to stimulate damaged retinal cells from within the retina to allow the cells to recreate visual signals that are processed and sent to the brain.
Therapies and Cures
Currently there is no cure for Usher Syndrome.
However, there are some studies and methods that seek to slow down / halt the deterioration, especially as regards retinitis pigmentosa.
As there are not certain and absolute solutions, all methods are considered stages of development and / or attempts, be it of scientific medicine in the western sense words whether alternative methods, not only by influences of oriental origin.
The informations on this website are in no way intended to be exhaustive and in any case we believe that the cure of Usher syndrome may rank among the personal paths involving the participation of the individual and thus its inclination towards a specific method rather another.
It is widespread practice in Western countries to trust only the results of scientific medicine, but in the case of the Usher syndromes, despite some promising discoveries, there are not the numbers to consider a way better than another in an unequivocal manner.
In over 20 years of living with the disease and its stages of progress, I have got to deal with different point of views and take part in some research. We believe that the opinions and choices are personal, but we try to provide as much clear information as possible for everyone to find their own guidance in choosing a therapy or another or none.
• CUBAN THERAPY FOR RETINITIS PIGMENTOSA
The International Center of Retinitis Pigmentosa, founded in 1992, provides specialized eye care for the diagnosis of eye diseases, especially treatment of Retinitis Pigmentosa
For the severe limitations posed to those who suffer, mostly young people, a team of Cuban scientists, led by Prof. Dr. Pelaez Molina, has been working for over forty years studying the therapeutic possibilities to stop progression of Retinitis Pigmentosa.
The treatment applied to the Retinitis Pigmentosa is performing a surgical technique associated with the application of ozone therapy, electrostimulation therapy, vitamin therapy. This surgery implants fatvascular orbital tissue in the suprachoroidal space, structure rich in blood vessels.
Cuba has a National focus on Retinitis Pigmentosa, led by Professor Peláez covering all provinces, which have been treated more than 6 000 patients and has allowed to know that 3.5 every 10 000 people with the disease.
All these years of experience and education are available at the International Center of Retinitis Pigmentosa “Camilo Cienfuegos”, where they have been treated approximately 4 365 patients from 78 countries. It also attend other ocular diseases such as: retinal dystrophy, diseases of the macula, eye diseases associated with retinitis pigmentosa, cataracts, glaucoma, myopia, other ametropia.
“Careful checks by non-Cuban specialists on many patients who have had these treatments have unfortunately found the complete ineffectiveness of this therapy. No improvement in functional parameters (visual field, visual acuity) was found. The same specialists do not exclude that these treatments may even be harmful. “ Abbattista Irene Gentile, Mauro Adenzato
• GENE THERAPY by Bennett J.
FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, PA 19104-6069, USA
The following informations are carefully selected, but the proof of thier truth is based on differend assumpions of the scientific methos, so it is hard to compare the results and the reliabilityof sources.
Some definitions are taken from DEAFBLINFINFO.ORG
USHER SYNDROME IS ONE OF THE CAUSES OF DEAFBLINDNESS
Deafblindness is a combination of vision loss and hearing loss that prevents access to communication, the environment, and people. A person who is DeafBlind may or may not have other physical or cognitive disabilities; each individual is different.
Deafblindness is a disability of access to sights, sounds, and information. All people with dual sensory loss face similar challenges, including:
• depending on others, to a certain extent, in order to feel safe and informed,
• learning and using communication strategies,
• becoming aware of and navigating their surroundings,
• finding social, living, and employment situations that fit their individual • talents, needs, and aspirations.
• Attitudinal Barriers that complicate their interactions with non-deafblind people.
Hearing loss causes difficulties communicating with people using spoken language, and vision loss causes problems using visual languages, such as sign language. With limited or no access to the sights, sounds, conversations, and interactions of the environment, you can imagine the difficulty DeafBlind people have in traveling around town, going shopping, and visiting the doctor.
However, when their needs are accommodated, people with dual sensory loss can live full, satisfying lives.
These are general issues related to the disability, especially in severe cases, but because it’s common for people who are deafblind to have some residual hearing and / or visual, there are psychological implications associated with
• acceptance of disability, especially in cases where the sensory difficulties appear at a young age
• awareness of the inevitable deterioration
• acceptance of aids. Hearing aids, white stick are symbols that reveal to everyone being different, although not visible to others.
• acceptance of one’s limits and non-self-sufficiency
• the disable affected by incurable retinitis pigmentosa is always wondering : Will I become blind? For how long will I still see? Will they find the cure before I completely lose sight?
IT IS IMPORTANT THAT DOCTORS ARE AS ACCURATE AS POSSIBLE IN THE DIAGNOSIS AND THEY PROVIDE ADEQUATE SUPPORT FOR PATIENTS AND THEIR FAMILIES.
Retinitis Pigmentosa is a highly disabling degenerative genetic disease that has major social consequences and relationship to the person concerned and / or whoever is next, whether relative, or friend.
When the disease emerges in childhood, becomes the fundamental role of parents, who themselves must be able to accept the disease and then to lead a “normal” life to their child without making him feel different from others. This is not a simple thing to implement, in fact often the normal attention of parents towards their children, even more if suffering from RP, it becomes overprotective putting them in a “gilded cage” and not promoting the socialization of these with their peers; all this has a negative impact at the time when they must face alone the challenges of life suddenly feeling “different” from others, often falling into depression. Attitude of other parents, it can be to hide the disease until the child grows and sometimes he finds out by himself and it is almost always when he is in the adolescent phase, already difficult in itself, where the young loses confidence in parents as a result of the fact that they hid the disease.
Another situation is when RP is diagnosed in older age. There is a big difference between those who are blind from birth, who realizes that there is a sensory perception unknown to him, but does not live this lack as a deprivation of his life facing social and relational life in complete normality. The diagnosis of RP made by an adult, even with a good residual vision, it sounds like some sort of conviction with no appeal to blindness. The impact of this new reality, it can produce attitudes ranging from depression to isolation, abandonment of the workplace and even the breaking of emotional bonds established previously, while the opposite may result in the denial of the disease pretending nothing, endangering himself and others such as continuing to drive a car. There is also who clinges to illusions, using numerous journeys of hope, the illusion of finding solutions to the problem, but these are constant sources of delusion, every time the person bringing a sense of frustration more and more accentuated.
The psychological life of RP patients is marked by certain situations that remind him of his handicap, some of these moments can be critical when, for example, during adolescence, does not go out at night with friends because he is ashamed to ask for the most enlightened place in pizzeria, or get help at the entrance of cinemas., while in the adult stage these events, we can identify them when to stop driving when you can not read anymore, when it comes time to be accompanied on his travels, etc. ..These situations can greatly affect the social life of the subject with others, coming to make him feel no longer able to protect his family, causing in some cases, isolation from the outside world, and then each of these moments can be the triggers to depression.
Another problem is that of family members, which may relate to the pathology of the joint in different ways, because even in the case of relatives or friends, there are behaviors like overprotectiveness, typical of the parents, the refusal of the disease, rarely having the right and balanced approach to the situations connected.
The discovery of RP is always a trauma for the whole family. The presence of a psychologist experienced in visual impairment at the time of diagnosis can help both the patient and his family members to overcome the initial shock. In addition, the therapist can help the family when the problems of daily life appear.
REad more: Understanding Usher Syndrome