Usher's syndrome: a description of the disease. Usher's syndrome (USH) - deaf blind child General provisions on the public offer

Date: 31.07.2020

People who have severe sensory impairments can have eye problems and hearing problems at the same time. According to statistics, 5-6% of these patients suffer from Usher's syndrome. This is a dangerous disorder that, unfortunately, does not respond to treatment. However, properly selected therapy can slow the progression of the disease.

Usher syndrome

This term is understood as a rare hereditary disease. This syndrome is characterized by hearing impairment and the development of retinitis pigmentosa. This violation provokes a progressive deterioration in vision.

Currently, there are several varieties of this pathology, each of which is characterized by certain features. In any case, if you suspect Usher syndrome, you should immediately consult a doctor.

Causes, risk factors

Usher syndrome is caused by a genetic mutation that is transmitted in an autosomal recessive manner. In order for the symptoms of the disease to appear, the child must receive the genes of both parents.

There are ten genes that can trigger the main constituents of the disease. These include:

- is a hearing loss associated with damage to elements of the inner ear, nervous system or auditory nerve.
Retinitis pigmentosa - consists in retinal dystrophy, which is provoked by a violation of photoreceptors or pigment epithelium. As a result, the person loses his sight.

Transmission of the disease is possible if both parents have it. Also, a child can get this ailment if the parents are carriers of the gene. If both partners have this gene, the risk of passing it on to the child is 1: 4.

If a person has only one disease gene, he becomes a carrier, but he himself has no symptoms of a violation. It is currently not possible to identify carriers.

If the baby is born to parents, one of whom is not a carrier of the gene, the risk of getting the disease is low. In this case, the child will definitely become the carrier of this anomaly.

Symptoms

Most people with Usher syndrome have. At the same time, visual impairments at the initial stages are accompanied by problems with perception in the dark. During adolescence, the so-called night blindness may appear.

As the body grows older, peripheral peripheral vision deteriorates more and more. Subsequently, it becomes a tunnel. At the same time, central vision is often not affected. However, the syndrome can develop over the years. After some time, central vision also deteriorates. However, Usher's syndrome does not provoke the development of total blindness.

It is impossible to answer how quickly a person loses his sight. This process is individual. That is why the degree of such violations is significantly different. The increase in the manifestations of the disease occurs gradually. Thanks to this, the person can prepare for the loss of vision.

Forms

Research by scientists has identified three main types of this pathology. Sometimes a fourth type of the disease is also detected, but it is extremely rare.

So, the main forms of the disease include the following:

The first type of pathology is accompanied. It is also typical for such people. Often, children take their first steps only at the age of 1.5 years. Vision begins to decline at about 10 years of age. At the same time, the final formation of night blindness is observed at the age of 20. In the presence of this type of disease, there is a risk of developing a progressive decrease in peripheral vision.
Pathology of the second type is characterized by moderate or congenital deafness. If a person is observed, hearing does not subsequently decrease. The development of retinitis pigmentosa is observed towards the end of adolescence or after 20 years. Night blindness begins to appear at the age of 29-31. With the development of an ailment of the second type, vision deteriorates more slowly than in the first case.
The third type of disease is accompanied, which usually begins during puberty. Also at this time, retinitis pigmentosa gradually begins to develop. It can cause progressive blindness.
Symptoms of the fourth type of pathology are more characteristic of men. In this situation, there are also growing impairments and loss of hearing and vision. This form of pathology occurs extremely rarely and, as a rule, has an X chromosomal origin.

Diagnostics

A combination of sudden hearing loss with progressively worsening vision helps to identify Usher syndrome. There are a number of instrumental studies that make it possible to make an accurate diagnosis:

Examination of the fundus - allows you to detect pigment spots on the retina. Also, during this examination, the doctor identifies the narrowing of the retinal vessels.
Electroretinogram - makes it possible to detect the first degenerative changes in the retina. With this procedure, the extinction of electroradiographic pathways can be detected.
Electronystagmogram - allows you to determine involuntary eye movements. They may indicate an imbalance.
- makes it possible to identify deafness and assess its severity.

The photo shows the changes that occur during Usher's syndrome

Currently, it is impossible to completely get rid of Usher's syndrome. Therefore, treatment is aimed at slowing down the process of decreasing vision and compensating for hearing loss. Possible therapies include the following:

Vitamin A intake. Some ophthalmologists claim that an increased amount of this substance can slow down the development of retinitis pigmentosa. However, it is impossible to completely stop this process.
Implanting electronic devices into the patient's ears. Cochlear implants or hearing aids can be used for this purpose.

Doctors advise adult patients with common types of retinitis pigmentosa to consume 15,000 IU of vitamin A palmitate every day. This should be done under the supervision of a specialist. Because people with type 1 Usher Syndrome were not included in the study, they should not take too much vitamin A.

At the same time, women planning a pregnancy should refuse to consume a large volume of this substance. This must be done three months before conception. Otherwise, the threat of congenital anomalies in the child increases significantly. Pregnant women also need to give up the high dosage of this substance.

A child with such a diagnosis must be adapted to life in society. This requires the help of psychologists and defectologists. In some cases, it is necessary to teach the baby sign language.

Unfortunately, Usher syndrome has a poor prognosis. Visual acuity and field of vision are lost in 20-30 years. In some cases, there is a risk of complete bilateral vision loss. accompanied by dumbness and rapidly develops to complete hearing loss.

How to adjust to life with Usher syndrome:

Usher syndrome is a very serious illness that cannot be completely cured. To slow the progression of the disease, it is very important to see a doctor in time. A specialist will diagnose and give recommendations for improving the quality of life.

Usher's syndrome (Ushera, eng. Usher syndrome, congenital sensorineural deafness and retinitis pigmentosa) is an autosomal recessive disorder that includes visual (retinitis pigmentosa) and auditory / vestibular disorders. The prevalence of Usher's syndrome varies from 4 to 17 per 100,000 people, represented by three clinical subtypes: USH1, USH2 and USH3, which differ in the severity of hearing impairment, the presence or absence of vestibular dysfunction, and the onset of retinitis pigmentosa.

Back in 1858, Von Graefe reported 5 cases of retinitis pigmentosa with hearing loss with a presumed recessive form of inheritance. Usher's syndrome is a rare disease; in the general population, it occurs with a frequency of 3 cases per 100,000. This syndrome is diagnosed in 5-8% of patients with hereditary deafness. Since the frequency of carriage of a mutant gene is 1 per 100 people with a recessive mode of inheritance, this syndrome rarely manifests. Diagnostic accuracy has increased with the advent of quantitative audiometry. True Usher syndrome is characterized by gross hereditary sensory-neuronal stable (possibly progressive) hearing loss associated with retinopathy pigmentosa, indistinguishable from retinitis pigmentosa, with significant speech impairment.

The characteristic symptoms of Usher syndrome are night blindness and narrowing of the visual fields that occur between the ages of 5 and 15 years. Some authors consider Usher syndrome to be genetically heterogeneous, while others consider it to be a phenotypic manifestation of retinitis pigmentosa. It is assumed that among the pathogenetic mechanisms of this disease, transmitted in an autosomal recessive manner, there are many trophic disorders that cannot be determined by a single gene. However, the occurrence of eye symptoms is associated with a mutation in the rhodopsin gene. Linkage analysis indicates the localization of the defect in the long arm of chromosome 4 in region 4 (q11-q13).

Currently, Usher's syndrome is a group of genetically heterogeneous diseases inherited in an autosomal recessive manner. According to clinical manifestations, there are three main types of disease , with the first two types including several forms.

First type Usher's syndrome is represented by 6 forms.
- Linkage analysis showed that the first form, named USH1A, is localized in the region of the long arm of chromosome 14 (q32.1-q32.3) between loci D14S78 and D14S250, but the gene has not yet been cloned.
- The second form, called USH1B, is the most common: it is diagnosed in about 75% of the total number of patients with the first type of the disease. This form was successfully localized on the long arm of chromosome 11q13.5, in the region of the DNA marker DUS533. In the same region, one of the VILA-type myosin genes was cloned. Screening of this gene for possible mutations showed their presence, the bulk of which led to the premature termination of protein synthesis.
- The third form of the first type, USH1C, was mapped in the region of the short arm of chromosome 11p15.1 and is associated with the D11S419 marker. In a candidate gene called harmonin, mutations were found that lead to the synthesis of a truncated protein that lacked its main domains.
- USH1D was able to map in the region of the long arm of chromosome 10 between loci D10S529 and D10S573.
- USH1E - linkage to DNA markers D21S1905 and D21S1913, located in the long arm of chromosome 21q21. The genetic distance between these markers is about 15 cm (centimorgan).
- USH1F, was mapped to chromosome 10 by genomic screening in the region of loci D10S199 and D10S596.
Second type Usher's syndrome includes 2 forms.
- The first of them, USH2A, was mapped in the region of the long arm of chromosome 1q41 between the DNA markers D1S237 and D1S229. A candidate gene named Usherin was cloned. The USH2A gene encodes a 1546 amino acid protein that contains the epidermal growth factor domains laminin and fibronectin type III. These domains were also found in other protein components of the basal lamina, extracellular matrix, and in adhesion molecules of cells. The study provides a characteristic of the intron-exon structure of the gene, consisting of 21 exons. Three mutations were found in the gene (239 = 242insCGTA, R334W, T1515M) and 12 polymorphic variants were described in patients with mild and severe forms of Usher's syndrome type II with progressive course and sensory-neuronal hearing loss. Further investigation of this gene revealed 15 new mutations in 57 unrelated probands, including three new missense mutations (C319Y, N346H, and C419F). It was found that 58 independent alleles of the USH2A gene out of 114 contain pathological mutations, of which the most common (in 16% of patients) observed - 2299delG, is major.
- In the region of the short arm of chromosome 3 (p24.2-p23), in the area of markers D3S1578, D3S3647, and D3S3658, the second form of the second type USH2B was mapped.

In two large families with type II Usher syndrome with mild retinitis pigmentosa, no linkage was found either with markers 1q41 or with chromosome 3q25, i.e. in these families, the USH2A and USH3 genes were not the cause of the disease. However, later it was found that in the phenotype of type II Usher syndrome with mild ophthalmoscopic manifestations of retinitis pigmentosa, which was not diagnosed until the third decade of life, there was a linkage with the D5S484 locus on chromosome 5q. Analysis of the haplotypes of the long arm of chromosome 5q indicates that the new locus is located between D5S428 and D5S433. To date, nine such families have been identified.

In 1996, 32 families with type III Usher syndrome (USH3) from a geographic isolate in Finland were examined. Linkage analysis made it possible to localize the disease in the long arm of chromosome 3 (q21-q25) between markers D3S1299 and D3S3625, the distance between which is about 1 cM (santimorgan).

Apparently, there is also a mitochondrial form of Usher's syndrome. The C12258A mutation in the mitochondrial MTTS2 gene was the cause of the development of retinitis pigmentosa in combination with a sensory-neuronal form of hearing loss. Work on mapping the genes of retinitis pigmentosa and syndromic forms continues.

In families with children with Usher syndrome, the risk of having a sick child is 25%.

There are 4 types of Usher syndrome:

type I - retinitis pigmentosa and total (absolute) deafness in the absence of vestibular functions;
type II - retinitis pigmentosa, partial deafness and intact vestibular function;
type III - retinitis pigmentosa, complete deafness, vestibular ataxia and, in some cases, psychosis (Hallgren's syndrome);
type IV - retinitis pigmentosa, total deafness and mental retardation.

Another variation of the classification is presented as follows:

gross retinopathy, accompanied by functional changes,
deep congenital slowly progressive sensory-neuronal hearing loss,
the presence or absence of a vestibular response to a thermal stimulus,
spinocerebellar status and higher cerebral function.

There are two types of Usher syndrome, depending on the age at which symptoms of night blindness appear.

The first type is characterized by difficulties in movement in low light conditions, arising at the age of 5-6 years,
in the second type, night vision impairment occurs at the age of 12-15.

Visual acuity changes in the same way as with retinitis pigmentosa. With pigmentation in the macular region, visual acuity decreases. The progressive type of the disease is often seen in patients with Usher syndrome who have good vision. Changes in the retinal pigment epithelium are similar to those in bovine-eye macular degeneration and hypopigmentation of the macular region, combined with retinitis pigmentosa.

In recent years, computed tomography has shown that patients with Usher's syndrome with profound deafness have cerebellar (cerebellar) atrophy of the occipital lobe, cavum septum pellucidum, cavum vergae, or decreased cerebellar circulation. The magnetic resonance picture shows a pathologically high signal, indicating the intensity of the damage to the midbrain and cerebellum. However, the revealed changes have little to do with the clinical symptoms of Usher's syndrome.

In studies carried out in the last decade, it was established that the regeneration of the kinetics of visual pigment in the fovea is impaired with normal light sensitivity and preserved visual acuity.

There is no cure for the syndrome ... However, patients should be handled by social workers, neuropsychiatrists, and caregivers, using techniques adapted for individualized teaching. In families with closely related marriages, in which there are patients with Usher syndrome, there is a high risk of having other sick children. However, the determination of the carriers of the pathological gene is still difficult, although in recent times the combination of hereditary traits (linkage) and the achievements of molecular genetics give hope.

Usher syndrome, congenital sensorineural deafness and retinitis pigmentosa) is a relatively rare genetic disease caused by a mutation of one of 10 genes, leading to congenital sensorineural hearing loss and progressive loss of vision (pigmentary degeneration). One of the main causes of deaf-blindness. Currently incurable. It is inherited in an autosomal recessive manner.

It is divided into three types:

Type I, occurs with a frequency of 3-6 per 100 thousand people, accompanied by congenital deep hearing loss or complete deafness and impaired vestibular functions, early onset of retinitis pigmentosa. Associated with mutations in genes CDH23, MYO7A, PCDH15, USH1C, USH1G. More common among Ashkenazi Jews.
Type II, accompanied by hearing loss that does not worsen over time, vestibular functions are not impaired. Retinal pigmentary degeneration begins at the age of 10-20 years. Associated with gene mutations USH2A, GPR98, DFNB31.
Type III, progressive deterioration of hearing and vision, in about half of the cases is accompanied by vestibular disorders. More common among Finns. Associated with mutations in the CLRN1 gene.

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Literature

C. H. Usher. On the inheritance of retinitis pigmentosa with notes of cases. Royal London Ophthalmological Hospital Report, 1914; 19: 130-336.
Stiefel SH, Lewis RA. The Madness of Usher "s: Coping With Vision and Hearing Loss / Usher Syndrome Type II. - Business of Living Publications, 1991. - ISBN 978-1-879518-06-3.
Duncan E, Prickett HT. Usher's Syndrome: What It Is, How to Cope, and How to Help - Charles C. Thomas, 1988 - ISBN 978-0-398-05481-6.
Vernon M. Answers to your questions about Usher "s syndrome (retinitis pigmentosa with hearing loss) - Foundation Fighting Blindness, 1986. - ISBN ASIN B00071QLJ6.
Vernon M. Usher "s syndrome: Deafness and progressive blindness: clinical cases, prevention, theory and literature survey. - Pergamon Press, 1969. - ISBN ASIN B0007JHOJ4.

Gene diseases

Usher's syndrome is characterized by moderate to severe congenital sensorineural hearing loss, vestibular hypofunction, and slowly progressive retinitis pigmentosa. In some patients, mental retardation and late psychoses may be observed.

It is estimated that one in 100 people carry the gene for this disease.

In the classic Usher syndrome, all patients have congenital sensorineural hearing impairment.

All patients are characterized by vestibular disorders, which are detected during the rotation test. In many, imbalance or atactic gait can be detected on clinical examination.

Retinal changes begin gradually. The first symptom of the disease is a violation of dark adaptation, which manifests itself in the form of night blindness. In the future, retinitis pigmentosa slowly progresses. By the age of 40-50, complete blindness develops.

To date, no effective treatment for Usher's syndrome is known. Therefore, the prevention of this serious hereditary disease by timely warning the family about the risk of re-birth of a sick child is of particular importance. This disease is inherited in an autosomal recessive manner, that is, parents of sick children who consider themselves healthy are latent carriers of the disease gene. This can be established or at least suspected using vestibular tests, electroretinography and audiometry.

Early diagnostics Usher's syndrome is extremely important for the correct planning of correctional and pedagogical measures for the teaching and upbringing of children with this disease. Children with Usher syndrome begin their education in schools for the deaf and hard of hearing.

41. Gene diseases. Martin Bell Syndrome.

Gene diseases is a large group of diseases resulting from DNA damage at the gene level.

Martin Bell Syndrome is one of the most common genetic disorders. The frequency of births of children with this syndrome is approximately 1 in 4000 newborn boys and 1 in 6000 girls. Basically, Martin-Bell syndrome is detected in boys (2-3 times more often in girls) and is more severe than in girls, although there are exceptions. Lighter forms in girls are associated with the compensating effect of the presence of the second X chromosome in the female karyotype (in men - XY, in women - XX).

The reason The development of the phenotype of Martin-Bell syndrome is a partial or complete cessation of the production of a specific protein as a result of the silence of a specific FMR1 gene in the X chromosome. The diagnosis of Martin-Bell syndrome can only be made by a geneticist using specific examination methods to detect this anomaly.

Disease transmission occurs through phenotypically healthy or clinically manifest male carriers. Further, men, carriers of premutation, pass on pre-mutation alleles to their daughters unchanged, and therefore they do not have pronounced mental retardation and other symptoms characteristic of this disease. The transition from premutation to mutation occurs during maternal transmission, that is, from mother to children. In addition, Martin-Bell syndrome is characterized by an earlier onset and more severe course of symptoms of the disease in subsequent generations.

Modern research shows that almost all people with Martin-Bell syndrome are lagging behind in intellectual development, but within this group, their intellectual level varies greatly - from slight lag to moderate and severe lag. And yet, most children with Martin-Bell syndrome can learn to walk, speak, read, write and, in general, do most of what other children can do, you just need to provide them with an adequate living environment and appropriate educational programs.

Today, taking into account the pathological mechanism of the mutant gene, drugs are beginning to be synthesized that can improve the condition of patients.

The prevalence of Usher syndrome among children with profound deafness ranges from 3 to 10%. According to the European Workshop on Usher Syndrome (1997), people with this disease account for up to 6% of all deaf people from birth and up to 50% of all deaf-blind adults.

Loss of vision is usually diagnosed around 10 years of age. Visual impairment progresses slowly. Complete blindness can occur at the age of 50-60. Ophthalmic examination reveals typical slowly progressive retinitis pigmentosa. Retinitis pigmentosa begins with an accumulation of pigment granules on the fundus, spreading towards the periphery. The fields of vision are slowly narrowed and visual acuity decreases in parallel. Other eye symptoms include cataracts and glaucoma.

Moderate to severe congenital sensorineural hearing loss is detected. In patients, atrophy of the organ of Corti and the epithelium of the inner and outer groove in the lower part of the basal curl of the cochlea is noted. Degenerative changes in the upper curl. There is a sharp atrophy of the spiral node, its peripheral and central fibers.

Defects of the vestibular system are found, which are expressed in imbalance when walking. The imbalance may be due to labyrinth disorders, not cerebellar pathology. In patients, in addition to the main symptoms, psychoses, aggressiveness, periodic depression are also revealed, in 25% - mental retardation.

The syndrome is inherited in an autosomal recessive manner. The gene is located on chromosome 14q.

The combination of deafness with retinitis pigmentosa was first described by A. Grafe in 1858, and the genetic nature of this syndrome was established by S. Usher in 1914. It was revealed that one in 100 people is a carrier of the gene for Usher's syndrome. In heterozygotes, there may be a lack of response to rotation, an increase in the dark adaptation threshold, or a slight decrease in vision.

Timely detection of retinitis pigmentosa in patients and the creation of adequate pedagogical conditions prevent stress conditions associated with loss of vision in a deaf person. There are no treatments available.