Usher syndrome

Usher syndrome is a hereditary disease that manifests itself as complete deafness from birth, as well as progressive blindness with age. Vision loss is associated with retinitis pigmentosa, a process of pigmentary degeneration of the retina. Many people with Usher syndrome also have severe balance problems.

Epidemiology

Thanks to the research, it was possible to establish that Usher syndrome affects about 8% of the examined deaf-mute children (tests were conducted in special institutions for deaf-mute people). Pigmentary retinitis was observed in 6-10% of patients suffering from congenital deafness, which, in turn, is observed in about 30% of people with pigmentary retina disease.

It is believed that this disease manifests itself in approximately 3-10 people out of 100 thousand worldwide. It can be observed in both women and men equally. About 5-6% of the world's population suffers from this syndrome. About 10% of all cases of childhood profound deafness occur due to Usher syndrome I, as well as II types.

In the United States, types 1 and 2 are the most common types. Together, they account for approximately 90 to 95 percent of all cases of Usher syndrome in children.

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Causes Usher syndrome

Usher syndrome types I, II, and III have an autosomal recessive cause, while type IV is considered an X-chromosome disorder. The causes of blindness and deafness that occur with this syndrome have not yet been sufficiently studied. It is assumed that people with this disease are hypersensitive to components that can damage the DNA structure. In addition, this disease may be associated with immune system disorders, but in this case, there is no exact picture of this process.

In 1989, chromosomal abnormalities were first identified in patients with type II disease, which may in the future lead to a way to isolate the genes that cause the syndrome. It may also be possible to identify these genes in carriers and develop special prenatal genetic tests.

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Risk factors

The syndrome is inherited when both parents are affected, i.e., it is inherited by a recessive type. A child can also inherit the disease if his parents are carriers of the gene. If both future parents have this gene, then the probability of having a baby with this syndrome is 1 in 4. A person who has only one gene for the syndrome is considered a carrier, but does not have symptoms of the disorder. Nowadays, it is not yet possible to determine whether a person has the gene for this disease.

If a child is born to parents, one of whom does not have such a gene, then the probability that he will inherit the syndrome is very low, but he will definitely be a carrier.

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Pathogenesis

The disease is considered a familial inherited genetic abnormality that is transmitted in an autosomal recessive manner.

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Symptoms Usher syndrome

Symptoms of Usher syndrome include hearing loss and abnormal accumulation of pigmented cells in the eye structures. The patient then develops degeneration of the retina, which causes vision deterioration and eventual vision loss in the most severe cases.

Sensorineural hearing loss can be mild or complete and usually does not progress from birth. However, retina pigment disease can begin to develop in childhood or later. Test results have shown that central visual acuity can be maintained for many years, even when peripheral vision deteriorates (a condition called "tunnel vision").

These are the main manifestations of the disease, which can sometimes be supplemented by other disorders, such as psychosis and other mental disorders, problems with the inner ear and/or cataracts.

Forms

During the research, 3 types of this disease were identified, as well as a 4th form, which is quite rare.

Type I of the disease is characterized by congenital complete deafness, as well as balance disorder. Often, such children begin to walk only at the age of 1.5 years. Deterioration of vision usually begins at the age of 10, and the final development of the state of night blindness begins at the age of 20. Children with this type of disease may develop progressive deterioration of peripheral vision.

In type II disease, moderate or congenital deafness is observed. In this case, deterioration in partial deafness often does not occur any more. Pigmentary retinitis begins to develop around the end of adolescence or after 20 years. The development of night blindness usually begins at 29-31 years. Visual acuity impairment in case of type II pathology generally progresses a little more slowly than in type I.

Type III of the disease is characterized by progressive hearing loss, usually beginning during puberty, as well as the gradual development during the same period (slightly later than hearing loss) of retinitis pigmentosa, which can become a factor in the development of progressive blindness.

Manifestations of type IV pathology mainly occur in males. In this case, progressive disorders and loss of hearing and vision are also observed. This form is very rare and usually has an X-chromosomal nature.

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Diagnostics Usher syndrome

Diagnosis of Usher syndrome is made based on the patient's observed combination of sudden deafness and progressive vision loss.

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Tests

A special genetic test may be ordered to detect the mutation.

Eleven genetic loci have been found that can cause the development of Usher syndrome, and nine genes have been identified that are definitely the cause of the disorder:

• Type 1: MY07A, USH1C, Cdh23, Pcdh15, SANS.
• Type 2: ush2a, VLGR1, WHRN.
• Usher syndrome type 3: USH3A.

NIDCD scientists, along with colleagues from universities in New York and Israel, have identified a mutation called R245X in the Pcdh15 gene that accounts for a large percentage of type 1 Usher syndrome in the Jewish population.

To find out about labs that perform clinical trials, visit https://www.genetests.org and search the lab directory for "Usher syndrome."

To learn about existing clinical trials that include genetic testing for Usher syndrome, visit https://www.clinicaltrials.gov and search for "Usher syndrome" or "Usher syndrome genetic testing."

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Instrumental diagnostics

There are several methods of instrumental diagnostics:

• Examination of the fundus to detect the presence of pigment spots on the retina, as well as narrowing of the retinal vessels;
• Electroretinogram, which allows to detect initial degenerative deviations in the eye retina. It shows the extinction of electroradiographic pathways;
• An electronystagmogram (ENG) measures involuntary eye movements that could indicate the presence of an imbalance.
• Audiometry, which is used to determine the presence of deafness and its severity.

Differential diagnosis

Usher syndrome must be differentiated from some similar disorders.

Hallgren syndrome, which is characterized by congenital hearing loss and progressive vision loss (cataracts and nystagmus also develop). Additional symptoms include ataxia, psychomotor disorders, psychosis, and mental retardation.

Alstrom syndrome, which is a hereditary disease in which the retina degenerates, resulting in loss of central vision. This syndrome is associated with childhood obesity. At the same time, diabetes mellitus and hearing loss begin to develop after 10 years.

Rubella in a pregnant woman in the first trimester can cause various abnormalities in the development of the child. Among the consequences of such an abnormality are hearing loss, as well as (or) problems with vision, and in addition to this, various developmental defects.

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Treatment Usher syndrome

There is currently no cure for Usher syndrome. Therefore, therapy in this case mainly consists of slowing down the process of vision loss, as well as compensating for hearing loss. Possible treatment methods include:

• Taking vitamin A (some ophthalmologists believe that high doses of vitamin A palmitate may slow, but not stop, the progression of retinitis pigmentosa);
• Implantation of special electronic devices into the patient's ears (hearing aids, cochlear implants.

Ophthalmologists recommend that most adults with common forms of retinitis pigmentosa take 15,000 IU (international units) of vitamin A palmitate daily under supervision. Because people with type 1 Usher syndrome were not included in the study, high doses of vitamin A are not recommended for this group of patients. People who are considering taking vitamin A should discuss this treatment option with their doctor. Other recommendations for this treatment option include:

• Changing your diet to include foods high in vitamin A.
• Women planning to become pregnant should stop taking high doses of vitamin A three months before they plan to conceive due to an increased risk of birth defects.
• Women who are pregnant should stop taking high doses of vitamin A due to an increased risk of birth defects.

It is also important to adapt such a child to social life. This requires the help of special education teachers and psychologists. In the event that the patient has begun to experience progressive loss of vision, he should be taught to use sign language.

Prevention

Prevention of this disease is considered to be the implementation of consultations and genetic tests in couples who have a family history of people with such a diagnosis at the stage of pregnancy planning.

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Forecast

Usher syndrome has an unfavorable prognosis. The visual field and its acuity begin to deteriorate in the period of 20-30 years in most patients with this disease of any type. In some cases, complete bilateral loss of vision occurs. Hearing loss, which is always accompanied by dumbness, very quickly develops to complete bilateral hearing loss.