Diagnosis: Usher syndrome

Usher syndrome is a genetic disorder characterized by sensorineural hearing loss or deafness and progressive vision loss due to retinitis pigmentosa. Sensorineural hearing loss is caused by abnormalities of the inner ear. Retinitis pigmentosa is an eye disease that affects the light-sensitive tissue layer at the back of the eye (the retina). Vision loss occurs as the retinal cells that detect light gradually deteriorate. Initially, night vision is lost, followed by the development of blind spots in the peripheral vision, which can enlarge and merge to create tunnel vision (loss of all peripheral vision). In some cases, vision is further impaired by clouding of the eye lens (cataracts).

Three main types of Usher syndrome have been described: types I, II, and III. The types are distinguished by the severity of symptoms and the age at which they appear. All three types are inherited in an autosomal recessive manner. Treatment for hearing loss may include hearing aids or cochlear implant surgery. Vitamin A palmitate can be beneficial in treating vision loss in individuals with Usher syndrome type II.

Usher syndrome was first described in 1858 by Albrecht von Graefe, but it was named after Charles Usher, a Scottish ophthalmologist who identified the hereditary nature of the disorder and its recessive pattern of inheritance.

Symptoms:
Studies show that central vision may remain clear for many years, even as peripheral vision declines. These narrowed visual fields are also referred to as “tunnel vision.” Balance problems occur in individuals with Usher syndrome types 1 and 3.

Usher Syndrome Type 1:
Characterized by profound hearing loss in both ears at birth (congenital deafness) and balance problems. Many affected children do not learn to walk until 18 months of age or later. Vision problems typically begin around age ten, although some parents report onset in children younger than ten.

Usher Syndrome Type 2:
Characterized by moderate to severe hearing loss in both ears at birth. In some cases, hearing loss may worsen over time. Night blindness usually begins in late childhood or early twenties. Peripheral vision loss continues, but central vision is generally preserved into adulthood. Visual problems in type 2 tend to progress more slowly than in type 1.

Usher Syndrome Type 3:
Characterized by later-onset hearing loss, variable balance (vestibular) dysfunction, and retinitis pigmentosa, which may appear between the second and fourth decades of life. Balance problems occur in approximately 50% of individuals with type 3.

Diagnosis:
Usher syndrome is caused by mutations in specific genes. To date, Usher syndrome has been associated with mutations in at least ten genes:

Usher Syndrome Type 1: MYO7A (USH1B), USH1C, CDH23, PCDH15 (USH1F), SANS (USH1G), and possibly CIB2

Usher Syndrome Type 2: USH2A, ADGRV1 (formerly VLGR1), WHRN (DFNB31)

Usher Syndrome Type 3: USH3A (CLRN1), HARS

These genes provide instructions for producing proteins involved in normal hearing, vision, and balance. Some of these proteins help specialized cells called hair cells transmit sound from the inner ear to the brain and detect light and color in the retina. The function of some proteins produced by genes associated with Usher syndrome is not yet fully understood.

Some individuals with Usher syndrome do not have mutations in any of these genes, suggesting that additional genes related to the condition likely exist but have not yet been identified.

All types of Usher syndrome are inherited in an autosomal recessive manner. Most genetic disorders are determined by the presence of two copies of a gene, one inherited from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disorder, they will be a carrier of the condition but typically will not show symptoms.

The risk that two carrier parents will both pass the altered gene to have an affected child is 25% for each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% for each pregnancy. The chance that a child will inherit normal genes from both parents is 25%. The risk is the same for males and females.

Parents who are closely related (consanguineous) have a higher chance than unrelated parents of carrying the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.

Usher syndrome affects approximately 3 to 10 per 100,000 people worldwide. Higher-than-average prevalence has been observed among Jews in Israel and Berlin, Germany; French Canadians in Louisiana; Argentinians of Spanish descent; and Nigerians of African descent. USH3, the rarest form in most populations, accounts for about 40% of Usher patients in Finland. Usher syndrome is the most common genetic disorder involving both hearing and vision abnormalities. Usher syndrome types 1 and 2 account for approximately 10% of all cases of moderate to severe childhood deafness.

Usher syndrome is diagnosed through evaluation of hearing, balance, and vision. Hearing tests (audiological exams) measure the frequencies and volumes of sounds a person can hear. Electroretinography measures the electrical response of light-sensitive cells in the retina. Retinal exams are performed to monitor the retina and other structures at the back of the eye. Vestibular (balance) function can be assessed using various tests that evaluate different parts of the balance system. Genetic testing is clinically available for most genes associated with Usher syndrome.

Therapy:
Treatment of Usher syndrome is focused on the specific symptoms present in each individual. Such care may require coordinated efforts from a team of specialists, including pediatricians or internists, specialists in hearing and balance disorders (otolaryngologists and audiologists), ophthalmologists for diagnosis and management of eye disorders, and/or other healthcare professionals.

Hearing impairment should be evaluated, and communication options should be explored as early as possible to provide the child with a solid language foundation. Hearing aids or cochlear implants will benefit most infants and children with Usher syndrome. American Sign Language can be considered as a communication option. Individuals who use visual signing often stop using tactile signing as their vision declines. Early intervention is crucial to ensure that children with Usher syndrome reach their full potential. Support services that may be helpful include specialized programs for children with sensorineural hearing loss or deafblindness, as well as other medical, social, and/or specialized services.

Currently, there is no known cure for retinitis pigmentosa (RP), although researchers are working on genetic and other therapies to repair or reverse the vision loss associated with RP and hearing loss. Some studies have shown that taking a specific daily dose of vitamin A can slow the progression of retinal degeneration in some people with typical RP and Usher syndrome type 2. Some experts recommend that adult patients with common forms of RP take 15,000 IU of vitamin A palmitate daily under the supervision of an ophthalmologist, maintain a balanced diet, and avoid high-dose vitamin E supplementation.

Because long-term supplementation with high doses of vitamin A (e.g., exceeding 25,000 IU) can cause adverse effects such as liver damage, patients should be regularly monitored by healthcare providers while on such supplementation. (Vitamin A is primarily stored in the liver.) It is essential that all patients with RP considering this supplementation consult their physician to determine whether it is appropriate in their specific case.

Individuals with RP associated with Usher syndrome may benefit from low-vision aids. Other treatment for Usher syndrome is symptomatic and supportive. Agencies that provide services for people with hearing and vision loss can be helpful.

Genetic counseling is recommended for affected individuals and their families.

Usher syndrome

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