Article: Usher syndrome

Usher syndrome is a genetic disease causing deaf-blindness. It is essentially progressive retinitis pigmentosa combined with congenital hearing impairment. It is inherited in an autosomal recessive pattern and is estimated to occur in 1 in 10,000 people. While this is a rare genetic condition, it represents the major cause of syndromic deafness with blindness. The condition gets its name from British ophthalmologist, C.H. Usher, who in 1914 wrote a paper describing several cases in which the link between congenital deafness and retinitis pigmentosa was stressed.

Usher syndrome is divided into three types: I, II and III. Children with type I syndrome are born profoundly deaf, and eyesight usually begins degrading after the first decade of life, beginning with night-blindness. They also experience degrading tunnel vision. If identified at a young age, children usually receive a cochlear implant, and some then use spoken language. Many use Sign language. When vision loss is severe or when one is blind one must use tactile signing. Problems with balance are present in people with Usher I and sometimes Usher III, due to the failure of the hair cells of the inner ear. Type II children are hard-of-hearing with stable hearing throughout their lives. Changes in sight in type II cases usually begin later, sometimes only becoming noticeable after the second decade of life. In the type III syndrome, hearing loss as well as retinitis pigmentosa can occur later in life. Hearing loss in Usher III is progressive.

Usher syndrome I

Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.

Mutations in the CDH23, MYO7A, PCDH15, Usher 1C (also known as Harmonin), and USH1G (now identified as SANS) genes cause Usher syndrome type I. Usher syndrome type I can be caused by mutations in one of several different genes. These genes function in the development and maintenance of inner ear structures such as hair cells (stereocilia), which transmit sound and motion signals to the brain. Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss. The genes also play a role in the development and stability of the retina by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the retinal pigmented epithelium. Mutations that affect the normal function of these genes can result in retinitis pigmentosa and vision loss.

Usher syndrome II

Usher syndrome type II occurs at least as frequently as type I, because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I.

Mutations in the MASS1 (also called VLGR1) and USH2A genes cause Usher syndrome type II. Usher syndrome type II may be caused by mutations in any of three different genes, two of which have been identified to date. These genes are called USH2A and MASS1. Usherin, the protein made by the USH2A gene, is located in supportive tissue in the inner ear and retina. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. The precise function of the protein made by the MASS1 gene is not yet known.

Usher syndrome III

The frequency of Usher syndrome type III is highest in the Finnish population, but it has been noted rarely in a few other ethnic groups.

Mutations in the USH3A gene cause Usher syndrome type III. Usher syndrome type III can be caused by mutations in one of at least two genes, only one of which (USH3A) has been identified. The USH3A gene makes a protein that is important for the development and maintenance of the inner ear and retina. The protein's function in these structures, and its role in hearing and vision loss, have not yet been fully explained.