Usher syndrome is a rare inherited disorder primarily characterized by deafness due to an impaired ability of the auditory nerves to transmit sensory input to the brain (sensorineual hearing loss) accompanied by retinitis pigmentosa, a disorder that causes progressive loss of vision. Researchers have identified three types of Usher syndrome and debated the existence of a fourth type. The age at which the disorder appears along with the severity of symptoms distinguishes the different types of Usher syndrome. Usher syndrome is inherited as an autosomal recessive genetic trait. The possible fourth type of Usher syndrome may be inherited as an X-linked genetic trait.
Usher syndrome is characterized by nerve deafness due to an impaired ability of the auditory nerves to transmit sensory input to the brain (sensorineural hearing loss) as well as abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (retinitis pigmentosa). Retinitis pigmentosa eventually causes degeneration of the retina leading to progressive loss of vision and in severe cases blindness. Sensorineural nerve deafness may be complete or mild, and usually does not progress. Retinitis pigmentosa may begin during childhood or later during life. Studies show that clear central vision may be maintained for many years even while side (peripheral) vision decreases, a condition known as “tunnel vision”. In some cases, these main symptoms of Usher syndrome may be accompanied by mental deficiencies, psychosis, disturbances in walking related to inner ear problems, and/or clouding of the lens of the eyes (cataracts).
Usher syndrome type I is characterized by complete hearing loss at birth (congenital deafness) and balance problems. In many cases, affected children do not learn to walk until 18 months of age. Vision problems usually begin at approximately the age of ten and development of night blindness at approximately at the age of twenty. Children with Usher syndrome Type I experience progressive loss of peripheral vision.
Usher syndrome type II is characterized by moderate to complete hearing loss at birth. In most cases, partial hearing loss will not worsen. Onset of retinitis pigmentosa occurs during the late teens or early twenties. Night blindness usually begins during the late twenties or thirties. Visual problems associated with Usher syndrome type II tend to progress more slowly than those associated with type I.
Usher syndrome type III is characterized by no hearing or balance problems at birth. Progressive hearing loss usually begins at puberty. Retinitis pigmentosa begins later during puberty, resulting in progressive vision loss.
Usher syndrome type IV predominately affects males and is also characterized by hearing loss and progressive vision disturbances. This is an extremely rare form of Usher syndrome and is thought to be inherited as an X-Linked trait.
Usher syndrome is inherited as an autosomal recessive trait in types I, II and III. Type IV Usher syndrome is thought to be inherited as an X-Linked recessive trait.
Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.
In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.
The exact reason for the hearing and vision loss in Usher syndrome is not well understood. Persons with Usher syndrome may have a hypersensitivity to compounds that can damage chromosomal components known as deoxyribonucleic acid (DNA). This suggests a defective DNA repair mechanism. Immune system disturbances are also thought to be associated with Usher syndrome, although the exact process is not well understood.
In 1989 researchers discovered the chromosome marker for Usher syndrome Type II. This discovery is expected to lead to the isolation of the genes that cause this disorder, identification of gene carriers, and perhaps, prenatal tests.
In 1995, researchers discovered the myosin VIIa gene which causes Usher syndrome Type 1B.
Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11.
The gene associated with Usher syndrome type 1A has been mapped to the long arm of chromosome 14 (14q32).
The gene associated with Usher syndrome type 1C has been mapped to the short arm of chromosome 11 (11p15.1).
The gene associated with Usher syndrome type 1D has been mapped to the long arm of chromosome 10 (10q).
The gene associated with Usher syndrome type 1E has been mapped to the long arm of chromosome 21 (21q21).
The gene associated with Usher syndrome type 1F has been mapped to chromosome 10.
The gene associated with Usher syndrome type IIA has been mapped to the long arm of chromosome 1 (1q41). In 1998, researchers discovered a protein that may cause Usher syndrome type IIA.
The gene associated with Usher syndrome type III has been mapped to the long arm of chromosome 3 (3q21-25).
Usher syndrome affects approximately three to ten in 100,000 people worldwide. Of the estimated 16,000 deaf-blind people in the United States more than half are believed to have Usher syndrome. Higher than normal numbers of people with Usher syndrome have been found among Jewish people in Berlin, Germany; French Canadians of Louisiana; Argentineans of Spanish descent; and Nigerian Africans. Usher syndrome is the most common disorder involving both hearing and vision abnormalities. Usher syndrome types I and II account for approximately 10 percent of all cases of profound deafness in children.
Usher syndrome was first described in 1858 by Albrecht Von Graefe, but was named for Charles Usher, a British eye doctor who focuses on the disorder’s hereditary nature.
A recent report from a collaborative study involving the National Institute on Deafness and Other Communication Disorders, Mt. Sinai School of medicine (NYC), Sackler School of Medicine, and the NYU Medical Center suggests that the identification of a particular mutation (R245X) of the Usher syndrome type 1 gene, may lead to earlier interventions on behalf of children with the disorder and to the identification of carriers of the disorder.
Screening for the significant mutation is now possible. Interventions that may improve the quality of life of the patient include help for the child before the symptoms of retinitis pigmentosa are obvious and earlier use of cochlear implants to ameliorate deafness associated with the disorder.
The treatment of Usher syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians or internists, specialists who assess and treat hearing impairment, physicians who specialize in diagnosing and treating eye disorders (ophthalmologists), and/or other health care professionals.
Sensorineural deafness should be assessed and treated as early as possible to help avoid possible speech problems as an affected child ages. Hearing aids may benefit some children with Usher syndrome. If vision loss occurs later in life, teaching a child sign language may have little value as a communication aid during adulthood. Therefore, educational methods and options should be chosen carefully during school years.
Early intervention is important in ensuring that children with Usher syndrome reach their potential. Services that may be beneficial may include special services for children with sensorineural deafness and other medical, social, and/or vocational services.
There is currently no known cure for retinitis pigmentosa (RP). However, researchers have shown that taking a specific daily dose of vitamin A may slow the progression of retinal degeneration in some people with typical RP (isolated RP; X-linked, autosomal recessive, or autosomal dominant RP) and Usher syndrome type II.
The six-year study, conducted at Harvard Medical School in association with the National Eye Institute (NEI) and the Foundation Fighting Blindness, evaluated vitamin A and E supplementation in 600 patients aged 18 through 49 years. The patients who supplemented their regular diets with 15,000 IU (international units) daily of vitamin A palmitate* had, on average, about a 20 percent slower yearly decline of retinal function when compared to those who received only trace amounts. (*Vitamin A palmitate is a specific form of vitamin A that is recommended for such treatment; experts indicate that beta-carotene, a natural precursor of vitamin A, is not an appropriate alternative for such supplementation.. The study results also suggested that taking 400 IU daily of vitamin E supplementation may be associated with a more rapid disease course.
Based on these results, experts recommend that most adult patients with common forms of RP take 15,000 IU daily of vitamin A palmitate under their ophthalmologists' care, follow a regular balanced diet, and avoid high-dose vitamin E supplementation. Because long-term high-dose vitamin A supplementation (e.g., exceeding 25,000 IU) may cause certain adverse effects, such as liver disease, patients should be regularly monitored by their doctors when taking such supplementation. (The body's reserves of vitamin A are primarily stored in the liver.)
Patients with less common disorders that may be associated with RP (e.g., other forms of Usher syndrome) were not evaluated in the study. In addition, certain patients with common forms of RP also were not included, such as patients with severely advanced RP and those younger than age 18 years. Thus, based on this study's results, recommendations cannot be made regarding vitamin A supplementation for these patients. Rather, they should be assessed on an individual basis, based on the specifics of their particular case. In addition, vitamin A supplementation may be inadvisable (contraindicated) for patients with certain preexisting medical conditions, including those who have high fasting blood levels of vitamin A; with increased sensitivity to vitamin A; who are prone to liver disease; who are planning to become or are pregnant (due to the potential of birth defects); or have certain other medical conditions. Thus, it is essential that any patients with RP considering such supplementation consult with their doctors for necessary evaluation to determine whether it is appropriate or inadvisable in their particular case.
For individuals with RP in association with Usher syndrome, low-vision aids may be helpful. In addition, genetic counseling will be of benefit for affected individuals and their families. Other treatment for Usher syndrome is symptomatic and supportive. Agencies that provide services to individuals with hearing and visual loss can be helpful.
Scientists are currently studying Usher syndrome to identify the location of the defective gene and a chromosomal marker. Once this gene is identified, researchers may then be able to develop effective treatment.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
A clinical study sponsored by the National Eye Institute to explore clinical and genetic aspects of Usher syndrome began in 2005. Further information, including criteria for participating in the study, is available through the previously noted NIH listing.
Researchers at the Medical College of Virginia and Gallaudet University are conducting a study funded by the National Institutes of Health to identify genes that cause hearing loss. They have established a DNA repository to store blood samples of people with deafness. People who are interested in participating in this study will be asked to provide information about their hearing loss, a family history, and a blood sample. Participation is free and does not require travel. For more information, contact:
Dr. Kathleen Arnos
Phone: (202) 651-5258
Toll Free: (800) 451-8834 Ext. 5258
Geneticists at the Boys Town National Research Hospital are conducting studies to identify the genes that cause Usher syndrome. Researchers at this hospital are actively involved in identifying the syndrome’s causes and seeking treatments. For more information, contact:
Boys Town National Research Hospital
Usher Syndrome Project
555 North 30th Street
Omaha, NE 68131
Toll-free (voice/TTY): (800) 835-1468
Fax: (402) 498-6331
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