Usher syndrome: what is it, symptoms, treatment, causes, prognosis

What is Usher Syndrome?

Usher syndrome (Usher's syndrome, eng. Usher syndrome) Is a rare genetic disorder primarily characterized by deafness due to impaired ability of the inner ear and auditory nerves to transmit sensory (sound) signals to the brain (sensorineural hearing loss) accompanied by retinitis pigmentosa, a disease that affects the retina of the eye and causes progressive loss vision. Researchers have identified three clinical types of Asher's syndrome. The age at which symptoms appear and the severity of the symptoms that distinguish the different types of Usher syndrome are determined by the underlying genetic cause. Usher syndrome is inherited as an autosomal recessive genetic trait.

The disorder was first described in 1858 by Albrecht von Graefe, but is named after Charles Usher (or Usher). a Scottish ophthalmologist who determined the hereditary nature of the disorder and the recessive pattern inheritance.

Signs and symptoms

Usher syndrome is characterized by deafness due to impaired ability of the inner ear and auditory nerves to transmit sensory (sound) signals to the brain (sensorineural / sensorineural hearing loss), as well as abnormal accumulation of colored (pigmented) material on a nerve-rich membrane (retina), lining the eyes (retinitis pigmentosa). Retinitis pigmentosa ultimately causes retinal degeneration leading to progressive vision loss and legal blindness. Sensorineural nerve deafness can be profound or mild, or progressive. Loss of vision caused by retinitis pigmentosa may begin in childhood or later in life and often first appears as vision problems at night or in low light (“chicken blindness"). Research shows that clear central vision can persist for many years even when lateral (peripheral) vision deteriorates. These narrowed fields of view are also called "tunnel vision". Patients with type 1 and type 3 Usher syndrome have problems maintaining balance (imbalance).

Type 1 Usher syndrome is characterized by profound hearing loss in both ears at birth (congenital deafness) and balance problems. In many cases, affected children cannot learn to walk until 18 months or later. Vision problems usually begin around the age of 10 through adolescence, although some parents report the onset of problems in children under 10 years of age. Usher syndrome type 2 is characterized by moderate to severe hearing loss in both ears at birth. In some cases, hearing loss can worsen over time. Night blindness occurs in adolescence or early 20s. Loss of peripheral vision continues, but central vision usually persists into adulthood. Vision problems associated with type 2 Usher syndrome tend to progress more slowly than problems associated with type 1.

Type 3 Usher syndrome is characterized by later hearing loss, variable imbalance (vestibular) and retinitis pigmentosa, which may appear between the second and fourth decade life. Balance problems occur in about 50% of patients with type 3 Usher syndrome.

Causes

Usher syndrome is caused by mutations in certain genes. So far, the disease has been associated with mutations in at least ten genes:

• Type 1:MYO7A (USH1B), USH1C, CDH23, PCDH15 (USH1F), SANS (USH1G) and, perhaps, CIB2 gene;
• Type 2: USH2A, ADGRV1 (formerly VLGR1) WHRN (DFNB31) genes;
• Type 3: USH3A (CLRN1), HARS genes /

These genes provide instructions for the production of 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 perceive light and colors in the retina. The function of some of the proteins produced by genes associated with Usher's syndrome is unknown.

Some people with Usher syndrome do not have mutations in any of these genes, so there are likely other genes associated with the condition that have not yet been identified.

All types of Usher syndrome are inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of two copies of a gene, one from the father and one from the mother. Recessive genetic disorders occur when a person inherits two copies of an abnormal (pathological) gene for the same trait, one from each parent. If a person inherits one normal gene and one gene for the disease, they will carry the disease but are usually asymptomatic. The risk for two carrier parents of passing on the altered gene and therefore having a sick child is 25% with each pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The probability that a child will receive normal genes from both parents and be genetically normal for this trait is 25%. The risk is the same for men and women.

Parents who are close relatives (blood relatives) are more likely than unrelated parents parents who have the same abnormal gene, which increases the risk of having children with a recessive genetic disease.

Affected populations

Usher syndrome affects about three to ten people in 100,000 worldwide. The number of people with Usher syndrome is above the average among Jews in Israel, Berlin, Germany; Louisiana French Canadians; Argentines of Spanish descent; and Nigerian Africans. Disease caused by mutations USH3, the rarest form in most populations, accounts for about 40% of patients in Finland. Usher's syndrome is the most common genetic disorder involving both hearing and vision. Usher syndrome types 1 and 2 account for approximately 10 percent of all cases of moderate to profound deafness in children.

Symptomatic disorders

Symptoms of the following conditions may be similar to those of Usher Syndrome. Comparisons can be useful for differential diagnosis:

• Alström syndrome - hereditary disease characterized by retinal degeneration with nystagmus and loss of central vision. This disorder is associated with obese in childhood. Sensorineural deafness and diabetes, usually develop after ten years.
• Rubella (German measles) is an acute viral disease that is of concern if caught during the first three months of pregnancy, as it can cause fetal abnormalities. These abnormalities can include hearing loss and / or visual impairment, as well as a child's malformation.
• Retinitis pigmentosa includes a large group of hereditary visual impairments that cause progressive retinal degeneration. Peripheral (lateral) vision gradually deteriorates and in most cases is lost over time. Under these conditions, central vision is usually retained until a late stage. Some forms of retinitis pigmentosa may be associated with deafness, obesity, kidney disease and various other common health problems, including central nervous system and metabolic disorders, and sometimes chromosomal abnormalities.

Diagnostics

Asher's syndrome is diagnosed based on tests of hearing, balance and vision. An auditory (audiological) examination measures the frequency and volume of sounds that a person can hear. An electroretinogram measures the electrical response of light-sensitive cells in the retina. Retinal examination is done to observe the retina and other structures in the back of the eye. Vestibular function (balance) can be assessed through various studies evaluating different parts of the vestibular system. Genetic testing is clinically available for most genes associated with Usher syndrome.

Standard treatments

Treatment for Usher Syndrome focuses on the specific symptoms that each person experiences. Such treatment may require the coordinated efforts of a team of healthcare professionals such as pediatricians or therapists, specialists who evaluate and treat disorders. hearing and balance (otolaryngologists and audiologists), doctors specializing in the diagnosis and treatment of eye diseases (ophthalmologists) and / or other specialists health care.

It is necessary to assess sensorineural deafness as early as possible and explore communication options so that the child has a solid language base. Hearing aids or cochlear implants are useful for most babies and children with Usher Syndrome. As an option for communication, you can learn sign language. Patients who visually show gestures often switch to tactile language as their vision deteriorates. Early intervention is essential for children with Usher Syndrome to reach their potential. Services that may be helpful may include special services for children with sensorineural deafness or deaf-blindness, as well as other medical, social and / or professional services.

There is currently no known cure for retinitis pigmentosa, although researchers are working on genetic and other treatments to restore or reverse vision loss associated with retinitis pigmentosa, as well as loss hearing. Some researchers have shown that taking a certain daily dose of vitamin A can slow down progression of retinal degeneration in some people with typical retinitis pigmentosa and Usher syndrome 2 types. Some experts recommend that adults with common forms of retinitis pigmentosa take 15,000 IU of palmitate daily vitamin A under the supervision of their ophthalmologists, eat a regular balanced diet and avoid high doses vitamin E. Because long-term intake of high doses of vitamin A (for example, exceeding 25,000 IU) can cause certain side effects such as liver diseasephysicians should monitor patients regularly when taking such supplements.

Other treatments for Usher syndrome are symptomatic and supportive.

Genetic counseling is recommended for patients and their families.

Forecast

The prognosis mainly depends on the progression of retinitis pigmentosa: in most cases, severe visual impairment occurs between the ages of 50 and 70 years.