What is Usher Syndrome Type I?
Usher syndrome type 1 is a genetic disease. It is inherited in a manner that geneticists call recessive. This means that an Usher 1 gene must be inherited from each parent in order for the child to have Usher type 1. In other words, both parents are carriers and they have a 1 in 4 chance of passing both copies of the Usher gene to each child.
People 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 are difficulty seeing in dimly lit areas - or night blindness - and a gradual loss of peripheral vision. These symptoms will generally begin in the teen years and continue through adulthood. Today, Usher syndrome is usually diagnosed before adulthood, but older people still 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. People with Usher type 1 often also have vestibular issues which manifest as an inability to balance normally. This can become more pronounced as their vision degrades. Balance issues manifest early in children with Usher type 1, as they often learn to walk later than their peers.
Carriers of Usher Type I
When only one Usher type I gene is passed on, half the normal amount of its protein is produced. It is believed that this is sufficient for normal vision and hearing as no clinical symptoms result. Certainly, there have been no reports of vision and hearing loss in those who are carriers for any of the Usher genes. However, there are theoretical reasons to think that there may be very mild hearing and vision problems that occur with older adults but to date this has not been studied.
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 walkers or late sitters. 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 on 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.