History

Usher syndrome is named after the British ophthalmologist Charles Usher, who examined the pathology and transmission of this illness in 1914 on the basis of 69 cases. However, it was first described in 1858 by Albrecht von Gräfe, a pioneer of modern ophthalmology. He reported the case of a deaf patient with retinitis pigmentosa, who had two brothers with the same symptoms. Three years later, one of his students, Richard Liebreich, examined the population of Berlin for disease pattern of deafness with retinitis pigmentosa. Liebreich noted that Usher syndrome is recessive, since the cases of blind-deafness combinations occurred particularly in the siblings of blood-related marriages or in families with patients in different generations. His observations supplied the first proofs for the coupled transmission of blindness and deafness, since no isolated cases of either could be found in the family trees.

Symptoms and subtypes

Usher syndrome is inherited in an autosomal recessive pattern. The genes implicated in Usher syndrome are described below.

Usher syndrome is responsible for the majority of deaf-blindness. The word syndrome means that multiple symptoms occur together, in this case, deafness and blindness. It occurs in roughly 1 person in 23,000 in the United States, 1 in 28,000 in Norway and 1 in 12,500 in Germany. People with Usher syndrome represent roughly one-sixth of people with retinitis pigmentosa.

Usher syndrome is inherited in an autosomal recessive pattern. "Recessive" means that both parents must contribute an appropriate gene for the syndrome to appear, and "autosomal" means that the gene is not carried on one of the sex chromosomes (X or Y), but rather on one of the 22 other pairs.

The progressive blindness of Usher syndrome results from retinitis pigmentosa. The photoreceptors usually start to degenerate from the outer periphery to the center of the retina including the macula. The degeneration is usually first noticed as night blindness (nyctalopia); peripheral vision is gradually lost, restricting the visual field (tunnel vision), which generally progresses to complete blindness. The qualifier pigmentosa reflects the fact that clumps of pigment may be visible by an ophthalmoscope in advanced stages of degeneration.

Although Usher syndrome has been classified clinically in several ways, the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness. Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as Finland and Birmingham. As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III. The function of these genes is poorly understood as of yet. The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the cochlea of the inner ear inhibit electrical impulses from reaching the brain.

Usher syndrome I

People with Usher I are usually born deaf and often have difficulties in maintaining their balance owing to problems in the vestibular system. Babies with Usher I are usually slow to develop motor skills such as walking. Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.

Usher syndrome type I can be caused by mutations in any one of several different genes: CDH23, MYO7A, PCDH15, USH1C, and USH1G. 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

People with Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I.

Usher syndrome type II may be caused by mutations in any of three different genes: USH2A, GPR98 and DFNB31. The protein encoded by the USH2A gene, usherin, is located in the 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 location and function of the other two proteins are not yet known.

Usher syndrome III

By contrast, people with Usher III experience a progressive loss of hearing and roughly half have vestibular dysfunction. 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 only one gene, the CLRN1 gene, have been linked to Usher syndrome type III. The CLRN1 gene encodes Clarin-1, a protein that is important for the development and maintenance of the inner ear and retina. However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is poorly understood as yet.

Differential diagnosis

Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness. Some preliminary studies have suggested that as many as 10% of congenitally deaf children may have Usher syndrome.[1] However, a mis-diagnosis can have bad consequences, e.g., if the parents elect to give the child cochlear implants.

The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations. An alternative approach is electroretinography (ERG), although this is often disfavored for children, since its discomfort can also make the results unreliable.[1] Parental consanguinity is a significant factor in diagnosis. Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking.

Individual cases

A 28-year-old woman with Usher syndrome, Rebecca Alexander, was profiled in Marie Claire in November 2007. After graduating from the University of Michigan with excellent marks, Alexander went on Columbia University, where she earned two master's degrees in public health and clinical social work. Today she is a social worker at a school for the deaf, and organizes seminars for the Foundation Fighting Blindness. She is also in private practice as a psychotherapist for eating disorders.

Christine "Coco" Roschaert[21] is a well-known person with Usher syndrome. She has published video blogs at Youtube,[22] , and recently was the kick-off speaker for the Deaf Awareness Week at the University of Vermont. In 2006, she graduated with a degree in Communication Sciences from Gallaudet University; there, she was a hunger striker in the 2006 protest organized by the Gallaudet United Now Movement. Roschaert is now in Nigeria founding the first deafblind program in that country.

A web-community, UsherLife, of people with Usher syndrome was founded on 1 February 2005 by Nick Sturley. Although centered on Great Britain, it offers resources to all people with Usher syndrome. The organization is hosting regular get-togethers in England, such as the Usher Hood Pub in Nottingham and a trip to Brighton pier. Other people with Usher syndrome have posted videos about their lives and condition on YouTube, most notably Ginny Paja-Nyholm.[27] In October 2007, Candice, a mom living in Texas, began blogging about her two daughters, Jasmine and Rebecca; Rebecca has Usher syndrome I.

Catherine Fischer has written a well-received autobiography of growing up with Usher syndrome in Louisiana, entitled Orchid of the Bayou. Similarly, Vendon Wright has written two books describing his life with Usher syndrome, I was blind but now I can see and Through my eyes. Louise Boardman has also written a short book called My son has Usher's Syndrome.

Christian Markovic, an artist living with Usher syndrome, runs a company, Fuzzy Wuzzy Designs.

Spencer Tracy's son John was a well-known person with Usher syndrome who lived a full life. The John Tracy Clinic was founded in 1942 by his mother Louise to offer free help to parents of hearing-impaired infants and preschool children.

(Source:  Wikipedia)