What is Usher Syndrome Type I?

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 I
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 I
Hearing loss in children with Usher syndrome type 1 is usually severe to profound and present at birth.

Vision in Type I
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 I
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 I
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 I 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.

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