chromosomes. American scientists K. Grader and E. Blackburn conducted a study to find out whether some previously unknown enzyme is involved in the formation of telomere DNA. On Christmas Day 1984, K. Greider discovered signs of enzymatic activity in the cell extract. The discovered enzyme was named by E. Blackburn and K. Greider telomerase. After isolating and purifying it, scientists found that it consists not only of protein, but also RNA, which contains the same sequence as the telomere. Thus, RNA serves as a template for building telomeres, while the protein component of the enzyme is required directly for enzymatic activity. Telomerase lengthens telomere DNA, providing a platform that in turn allows DNA polymerases to copy a chromosome along its entire length without losing genetic information. Thus, the chromosome is not shortened when copied.

E. A. Chistyakova

Hereditary anomalies of vision and hearing - genetic basis, treatment and prevention

The problem of human health and genetics are closely interrelated. Genetic scientists are trying to answer the question of why some people are susceptible to various diseases while others remain healthy under the same conditions. This is mainly due to the heredity of each person, that is, the properties of his genes, which are located in the chromosomes.

Heredity has always been one of the most difficult to explain in human history. Even in ancient times, people unconsciously used genetic methods in breeding plants and animals, and in relation to humans, there were life observations related to the inheritance of various traits: hair color, eyes, shape of the ear, nose, lips, height, physique, inheritance of deformities observed in representatives one family.

Many scientists have put forward their hypotheses about the occurrence of hereditary pathologies. However, their assumptions were not based on scientific observation. In the XX century. with the development of the science of "genetics" it was clarified and scientifically confirmed that such pathologies are of a hereditary nature. The study of hereditary diseases is engaged in a science called "medical genetics".

The relevance of this topic is due to insufficient knowledge of the etiology (causes and conditions of the onset of diseases) and pathogenesis (the mechanism of the onset and development of diseases) of congenital anomalies of vision and hearing. These diseases have various forms. Let's take a quick look at each of them.

1. Hereditary anomalies with simultaneous impairment of vision and hearing or deaf-blindness - congenital or acquired in early age(before mastering speech) blindness and deafness, as well as dumbness associated with a lack of hearing. Without special training, a deaf-blind-mute child does not develop mentally, does not acquire basic self-care skills. Therefore, for the deaf-blind, the possibility of development is realized in the process of special education.

The most common syndromes of hereditary combined vision and hearing anomalies: Usher, Marshall, Treacher Collis, Cruson, Alport syndromes.

2. Hereditary anomalies of hearing without visual impairment.

Congenital malformations of the outer and middle ear in childhood are quite common. On average, up to 400-500 children with this pathology are born in our country every year. Among different types pediatric ENT pathology, congenital malformations of the ear make up approximately 5-6%.

The mental development of a deaf child is different depending on whether his deafness is congenital, whether he lost his hearing in the early stages of ontogenesis. The taxonomy of disturbances in the sensory sphere takes into account the criteria of time and degree of damage. Among children with hearing impairment, the following stand out:

1) deaf: a) deaf early; b) late deaf;

2) hearing impaired: a) with relatively intact speech; b) with deep speech underdevelopment.

Diseases in which there are abnormalities in the development of hearing: macrotia with atresia of the external auditory canal, Pendred, Richards-Randal, Jervell and Lange-Nielsen, Waa-denburg syndromes.

3. Visual anomalies without hearing impairment.

Some patterns of visual impairment are similar to hearing impairments. With a hereditary disease, the child does not receive a certain amount of visual representations. Difficulties arise in "arising" vertical position bodies, fear of space and new objects, can lead to a delay in the development of space and some activity. The first manipulations and individual actions with the object appear in blind children only after two years.

Visual impairment at an early age, even at the level of low vision, also causes underdevelopment of the psychomotor sphere: weakness in the act of grasping is noted, differentiation of movements is delayed, freezing is observed, or, conversely, unnecessary stereotypical movements of the head and hands.

However, the development of a child who lost his sight at an older age is developing in a completely different way. The available past experience of visual impressions facilitates the development of motor skills, object activity, the formation of ideas and concepts.

Among children with visual impairment, there are:

a) totally blind;

b) partially seeing;

c) visually impaired.

The frequency of detected congenital pathology of the organ of vision is 2-4%. Genetic changes are responsible for 50% of blindness in children.

The most common hereditary diseases leading to visual impairment or blindness: Rieger, Alstrom, Lenz, Apert, Marfan syndromes.

Thus, we see that diseases with a hereditary predisposition are a large diverse group of diseases, the development of which is due to the interaction of certain hereditary factors (for example, mutations). The basis of hereditary predisposition is a wide polymorphism of the human population in enzymes, structural and transport proteins, antigens, which ensures the genetic uniqueness of each person.

Thanks to the progress of medical genetics and the expansion of ideas about the nature of inheritance of all kinds of diseases, the manifestation of mutant genes, the ways of treatment have become much clearer, and most importantly, the prevention of hereditary diseases is the most important task of medical genetics. It allows you to timely prevent the birth of sick children. Prevention of hereditary diseases is carried out mainly through medical genetic consultations and diagnostic centers.

General approaches to the treatment of hereditary diseases are similar to those to the treatment of diseases of any other etiology. In the treatment of hereditary pathology, the principle of individualized treatment is preserved. This principle is especially important, since hereditary diseases are heterogeneous, and with the same clinical picture different hereditary diseases with different pathogenesis can occur. Depending on the genotype, conditions of pre- and postnatal ontogenesis, the manifestation of mutations in

specific individual can be modified. In the treatment of hereditary diseases and diseases with a hereditary predisposition, the following areas are distinguished:

Symptomatic (effect on symptoms);

Surgical (correction, removal or transplantation of organs and tissues);

Pathogenetic (effect on the processes occurring in the body during diseases);

Etiological (or etiotropic - treatment aimed at eliminating the cause of the disease).

There are some types of prevention of hereditary pathology.

1. Primary prevention involves actions that prevent the birth of a sick child. This is realized through planning childbirth by choosing the optimal reproductive age, refusing to bear children in cases of high risk of hereditary and congenital pathology. About 20% of all hereditary diseases in each generation are diseases caused by new mutations.

2. Secondary prevention is carried out by termination of pregnancy in case of high probability of fetal disease or prenatally diagnosed disease. Termination of pregnancy is currently the only practically feasible method of prevention for most severe and fatal genetic defects.

3. Tertiary prevention of hereditary pathology means the correction of the manifestation of pathological genotypes. With its help, it is possible to achieve complete normalization or decrease in the severity of the pathological process. Prevention of the development of a hereditary disease includes a set of therapeutic measures that can be carried out in utero or after birth. In this case, preventive measures are closely related to the treatment of hereditary diseases, and there is no clear border between them.

Hereditary hearing loss - hearing impairment inherited in a family that has cases in previous generations hearing loss... The reason is the inheritance of altered genes. You probably already know that genes are carriers of hereditary information that determines the development of all living things. All genes carry the information necessary for the development of an entire organism from a single fertilized egg. Each gene individually is responsible for the formation of a specific protein. Proteins build the entire body. We all get two copies of each gene: one from the mother, the other from the father. Thus, every person has two variants of the same gene. A number of genes in the body are responsible for the formation and functioning of the organ of hearing. In total, there are at least 100 such genes. It is not surprising that, according to recent studies, more than 50% of all cases of congenital and early childhood hearing loss are associated with hereditary causes. It is believed that every eighth inhabitant of the Earth carries one of the genes that cause recessive hearing loss.

What is the most common type of hereditary hearing loss?

About 75% of all cases of hereditary hearing loss are attributed to recessive non-syndromic hearing impairment (RHND) or recessive non-syndromic hearing loss.

With a recessive type of inheritance, the child receives from each of the parents the same variant of the gene that causes this form of hearing impairment. The "recessive" gene is manifested only in conjunction with another gene of the same and causes RNNS. At the same time, the child's parents do not suffer from hearing impairment, since they have a normal variant of this gene in a pair of genes received from their parents. However, they are carriers of the gene recessive non-syndromic deafness... Thus, a child may have a hearing impairment, while his parents and all other relatives may have normal hearing at any age.

The non-syndromic form is understood as the fact that hearing loss is not accompanied by other signs or diseases of other organs and systems, which would be inherited along with hearing loss, which occurs in syndromic forms. For example, Pendred's syndrome - the most common syndromic variant of hearing loss - is a recessive disease characterized by a combination of hearing impairment with the formation of euthyroid goiter. Goiter develops during adolescence and later, so in children differential diagnostics Pendred's syndrome and non-syndromic recessive hearing loss is extremely difficult.

Autosomal dominant forms non-syndromic hearing loss are relatively rare, and account for no more than 25% of all non-syndromic deafness. In dominant forms, one altered copy of the gene is enough for the disease to manifest. In such cases, as a rule, one of the parents is ill in a child with hearing loss, but a new mutation is also possible.

How does the child receive RNNS?

So, each of us gets half of our genes from our father and the other half from our mother. Which gene from the parental pair of genes we get is a purely random phenomenon.

From time to time, exposure to any factor can cause a gene change. Geneticists call this change a mutation. Many people are unaware that they are carriers of altered genes. These changes, once emerging, are inherited from generation to generation. Most mutations do not affect the state of the body, but sometimes some of them, for a number of reasons, manifest their effect. One of the reasons is the meeting of two carriers of the same altered gene. They may be the parent of a child with recessive non-syndromic deafness. This child receives the altered gene from each parent and thus will have two copies of the altered gene. Only in this case, due to the absence of a normal variant of the gene, the mutation manifests its effect. For these parents, the risk of having a child with congenital non-syndromic deafness is 25%. Typically, the degree of hearing loss is initially sufficient for correction and training. Children with normal hearing in a given marriage can be born in 75% of cases, and some of the children can have a healthy genotype (25%) and nothing threatens them in the future, while others, like their parents, are carriers of the altered gene (50%) and for them the situation may repeat itself.

Marriage of two hearing parents, carriers of the altered gene

The most significant for the development of hearing loss was connexin-26 gene (GJB2)... Only one change in this gene, referred to as the 35delG mutation, is responsible for 51% of all cases of congenital and early childhood hearing loss. There are other known changes in this gene. Thanks to the research carried out, it is known that in our country every 20 inhabitant is a carrier of the 35delG mutation. Therefore, sadly, the likelihood of meeting carriers of the altered gene is quite high.

What benefit is expected from the identification of genes leading to RNNS?

This is the ability to pinpoint the causes of hearing impairment. Genetic analysis makes it possible to make a correct prognosis of the recurrence of the disease in the family, as well as to assess the likelihood of having children with hearing impairment in the families of relatives. Early detection of a genetic defect helps to timely choose the right tactics for treating and rehabilitating a child with hearing impairment, and will save him from taking unnecessary medications.

Even a healthy person can find out his genotype, since he may be a carrier of the hearing loss gene (with a probability of 1/20). Research on the carriage of the hearing loss gene is especially important for people who have relatives with hearing impairment, as well as spouses who are in a closely related marriage.

For a married couple in which both are carriers of a mutation in the hearing loss gene (regardless of whether they already have a child with hearing impairment or not), it is possible to carry out prenatal (prenatal) DNA diagnostics of the disease in the fetus at an early stage of pregnancy (9 -12 weeks).

How is the search for genes leading to RNNS carried out?

More than half of cases of congenital RNNS are due to homozygous and compound heterozygous recessive mutations in the gene GJB2 (hearing loss of genetic type DFNB1: OMIM 220290 ). The frequency of this genetic type of hearing loss is 1: 1000 newborns. Some rare specific mutations in a gene GJB2 show a dominant-negative effect and, in a heterozygous state, lead to autosomal dominant non-syndromic hearing loss (DFNA3A: OMIM 601544 ) or syndromes keratitis-ichthyosis-deafness (OMIM 148210 ), Fovinkel (OMIM 124500 ), Bartha Pumphrey (OMIM 149200 ), palmar-plantar keratoderma with deafness (OMIM 148350) ... At the Center for Molecular Genetics, it is determined whether the patient has mutations in the gene GJB2... This study includes search for the 8 most common mutations in a geneGJB2 (c.35delG, c.-23 + 1G> A (IVS1 + 1G> A), c.101T> C (p.Met34Thr), c.313_326del14, c.235delC, c.167delT, c.358_360delGAG (p. Glu120del) and del (GJB2-D13S175)), accounting for 95% of the total number of chromosomes with a mutation in the gene GJB2, by allele-specific MLPA; and search for mutations in a geneGJB2 by sequencing mRNA sequences (exons 1 and 2) and exon-intron gene junctions. The applied approach allows detecting more than 99% of mutations in the gene GJB2... If necessary, carried out search for a long deletion 309-kb del (del ( GJB6) -D13S1830) at the locusDFBN1.

In patients with HNS without gene mutations GJB2 mutations are observed in other genes: more than 100 genes responsible for HHC have been described. The Center for Molecular Genetics is searching for mutations of 32 of the most common genetic forms of HNS and syndromes masquerading as them in patients without mutations in the gene. GJB2 method sequencing panel of 32 genes presented in the Table.

When carrying out prenatal (prenatal) DNA diagnostics for a specific disease, it makes sense to diagnose frequent aneuploidies (Down, Edwards, Shereshevsky-Turner syndromes, etc.) on the already available fetal material, paragraph 54.1. The relevance of this study is due to the high total frequency of aneuploidies - about 1 per 300 newborns, and the absence of the need for re-sampling of fetal material.

Universal newborn screening programs, which involves electrophysiological testing of hearing function in all newborn babies before discharge from the hospital, have been legislated or voluntarily adopted throughout the United States. And although these programs have made possible the early detection of hearing loss in many, many children, they will never be able to detect absolutely all cases of congenital hearing loss, since very often genetically determined hearing loss does not begin to manifest itself immediately after birth.

Early hearing loss diagnostics makes it possible to carry out earlier therapeutic measures (speech therapy, hearing aids, cochlear implantation), which make it easier to acquire speech and language skills, and improve academic results.

In developed countries hereditary forms make up about 60% of all forms of hearing loss. More than 400 genes have been identified that are responsible for the development of hearing loss. Of all hereditary forms of hearing loss, about 70-80% are non-syndromic forms (the remaining 20-30% are syndromic forms).

Term congenital hearing loss implies that hearing is impaired from birth, for example, with congenital cytomegalovirus infection. Hereditary hearing loss can manifest itself at birth and after it, in some cases even after many years. Hearing loss can be unilateral and bilateral, progressive and non-progressive. The degree and nature of hearing loss with different genetic defects will be different. Sometimes they can vary even within the same genetic disease.

a) Mendelian inheritance of hearing impairment (deafness)... Mendelian types of inheritance include autosomal dominant (AD), autosomal recessive (AR), X-linked recessive and X-linked dominant. In the case of autosomal dominant inheritance, often one spouse (sick) is heterozygous (one allele of the gene is changed, the other is not), and the second spouse (healthy) is homozygous (both alleles are not changed).

If we let's see on the so-called Pennett lattice in this situation, we will see that the probability that a descendant with hearing loss will be born is 50%. A offspring that does not inherit the Dd genotype will not carry the allele responsible for the formation of hearing loss. When assessing family history, it is usually found that the gene is transmitted vertically, i.e. the gene manifests itself in several successive generations.

At autosomal dominant inheritance gender in most cases does not matter, therefore, hearing loss can be transmitted with equal probability from parents of both sexes. When constructing a Pannett grid for two sick parents with the Dd genotype, we will see that the probability of a sick homozygous DD offspring is 25%, the probability of a sick heterozygous Dd offspring is 50%, the probability of a healthy homozygous dd offspring is 25%. The phenotype of a sick person with the DD genotype will usually be more severe than the phenotype of the heterozygous Dd offspring. A healthy, homozygous offspring of dd will not transmit the disease to their children.

When bound with a certain condition genotype(for example, Dd) is not accompanied by its manifestation (for example, hearing loss), it is believed that the genotype has incomplete penetrance. Expressiveness refers to the variability of phenotypes that can be associated with a single genotype (eg, Dd); thus, two people with the same genotype may have different phenotypes.

At autosomal recessive inheritance usually both parents are healthy heterozygotes (one altered allele and one normal allele). In this case, looking at the Pannett lattice, we will see that with a probability of 25% the child will develop hearing loss, and with a probability of 50% he will be a carrier. When assessing a family history, it usually turns out that hearing loss is transmitted "horizontally", i.e. occurs in several members of the same generation, but not in several successive generations. As with autosomal dominant inheritance, gender in most cases does not matter, therefore, hearing loss can be transmitted with equal probability from parents of both sexes.

If marriage concluded between sick parents who are homozygous for a recessive trait (rr), which means that the probability of the birth of a descendant with hearing loss is 100%.

At X-linked recessive inheritance the disease manifests itself in the phenotype in men with an altered allele on the X chromosome, and in women with two copies of the altered allele. The most common transmission is from a female carrier and a healthy father. According to the Pannett table, built for X-linked recessive inheritance, the probability of such a case of having a carrier girl is 50%, the probability of having a sick boy is also 50%. A sick man will never pass the disease on to his sons; the boy will receive a healthy Y chromosome from his father and an X chromosome from his mother.

Carrier woman can transmit the altered allele to both daughter and son. In the presence of a sick male (xY) and a female carrier (xX), the probability that the boy will suffer from hereditary hearing loss is 50%, the probability that the girl will suffer from hereditary hearing loss is 50% (xx), the probability that the girl will the carrier also equals 50%.

X-linked dominant inheritance is much less common than X-linked recessive. In X-linked dominant inheritance, marriage usually occurs between a sick woman with the xX genotype and a healthy man with the XY genotype. As with autosomal dominant inheritance, in the presence of the xX genotype, the disease will manifest itself in a phenotype. The table below shows the Pannett Lattice for a sick woman (usually a heterozygote) and a healthy man. The probability that a female offspring will suffer from hearing loss is 50% (genotype xX), and the probability that a male offspring will suffer from hearing impairment is also 50% (genotype xY). Consider a marriage situation between a healthy woman (XX) and a sick man (xY).

In this case 100% female descendants will be deaf, because they receive the altered dominant allele x from the father, but at the same time all 100% of the male offspring will be healthy, because they receive the unmodified X allele from the mother.

At X-linked dominant inheritance the phenotype is more pronounced in men than in women. In women with the xX genotype, one allele turns out to be normal, while in men there is only one altered allele on the X chromosome, as a result of which the altered gene begins to synthesize a pathological protein (or disrupt its synthesis).

By improving the language the deaf and dumb and the emergence of schools for the deaf, deaf people have the opportunity to communicate more closely with each other, as a result of which the number of marriages between them (assortative crossing) has increased. Patients suffering from hereditary recessive hearing loss are homozygotes for the same altered allele. Consequently, 100% of their offspring will be deaf. Such marriages, in which 100% of the offspring are deaf, are called non-complementary. "Complementary" is a marriage in which all descendants of parents with various forms hereditary deafness (either between parents with acquired deafness, or between one parent with acquired deafness and another with autosomal recessive deafness) will have normal hearing.

b) Mitochondrial inheritance of hearing impairment (hearing loss)... DNA is found not only in cell nuclei, but also in the mitochondria of the cytoplasm. Mitochondria provide cells with energy in the form of adenosine triphosphate (ATP), and also participate in other cellular processes (cell differentiation, apoptosis, signal transmission). Each cell contains many mitochondria. If a cell contains mitochondria with altered and normal DNA, this condition is called mitochondrial DNA heteroplasmy. If the cell contains only mitochondria with altered DNA, this condition is called mitochondrial DNA homoplasmy. With homoplasmia, symptoms are usually more severe and appear earlier than with heteroplasmia. Heteroplasm is more common than homoplasm; Since the number of altered mitochondria can be different, in heteroplasmy, the variability of phenotype expression is higher than in homoplasmy.

Mitochondrial DNA is inherited only from the mother, not from the father, because mitochondrial DNA is found in the eggs, but not in the sperm. Mitochondrial hearing loss accounts for about 1% of all cases of prelingual hearing loss and 5-10% of all cases of postlingual, non-syndromic hearing loss.

v) Non-syndromic hearing loss... In most cases (70-80%), hereditary hearing loss is non-syndromic. Of these, approximately 65-75% are inherited in an autosomal recessive manner. The locus of each gene associated with autosomal recessive non-syndromic hearing loss is labeled DFNB and an Arabic number.

Hearing loss associated with damage to connexin proteins... Most often, non-syndromic hearing loss, inherited in an autosomal recessive manner, is associated with mutations in the family of connective proteins, especially the gap junction protein (36, gap junction protein) gene GJB2, which codes for connexin 30. Mutations in the GJB2 gene can cause up to 50 % of all cases of severe non-syndromic hearing loss inherited in an autosomal recessive manner Connexin genes are responsible for the formation of gap junction proteins, which are responsible for the reuptake of potassium ions after sensory stimulation of cochlear hair cells.

Most frequent mutation of the connexin family is the GJB2 mutation, the most common connexin 26 mutation is 35delG / 30delG (most common in Europeans and white Americans). The 167delT mutation is most often found in Ashkenazi Jews, 235delC in Asians, R143W in some African populations, W24X in Spaniards, Slovaks, and some Indians. So far, about 90 different GJB2 mutations have been identified. Although most of them are associated with non-syndromic autosomal recessive hearing loss, some of the GJB2 mutations are associated with syndromic forms of hearing loss that are inherited in an autosomal dominant manner (for example, Fowinkel syndrome or ectodermal dysplasia in keratitis-ichthyosis-hearing loss syndrome).

Congenital and acquired persistent hearing impairments

1. Analysis of the structure of the disease.

According to various literary sources, from 4 to 6% of our planet suffer from one or another hearing impairment. Let us assume, in accordance with Academician N.A. Preobrazhensky, that the total number of the deaf and hard of hearing is 5%. If we count one hundred, the population of the Earth has already reached 5 billion. people, then the number of people of all ages with hearing impairments will amount to 250 million. It is close to the population of a country like the United States. Given the socio-psychological nature of such a condition as hearing loss, this problem is undoubtedly of particular importance in childhood. Domestic and many foreign otorhinolaryngologists pay attention to the pronounced dependence of the distribution and nature of various hearing damage on the age of children. An analysis of the medical history made it possible to establish that the majority of children - 82% - suffer from the organ of hearing in the first two years of life, i.e. before the development of speech and during its formation.

With the presence of a structure of diseases of the hearing organs, according to the data of the regions of Russia in 1991-1992. the sensorineural form of hearing loss prevailed (72.6%), conductive hearing loss was diagnosed in 13.3%, mixed - in 14.1% of patients. In subsequent years, the picture changed due to an increase in the number of children with conductive and mixed forms of hearing loss. Persistent hearing impairment - impairment of auditory function that does not show significant improvement, both independently and as a result of treatment, i.e. are irreversible.

The causes of persistent hearing impairment in childhood can be divided into three groups: hereditary, congenital and acquired.

1. Hereditary disorders.

Genetic hearing disorders are manifested by deafness and hearing loss. Hereditary hearing loss is sensorineural, characterized by irreversible changes in the structures of the auditory system. Her usual characteristics are:

Bilateral impairment of sound perception;

Involvement in the pathological process of the organ of Corti;

Lack of vestibular disorders.

Deafness is most often hereditary. In 37%, deafness is transmitted in a recessive manner, in 12% - in a dominant mode, in 2% - deafness is sex-related.

Hereditary deafness is divided into two categories:

Hearing impairment as a monosymptom;

Hearing damage as a secondary syndrome in a complex of lesions of various organs and systems.

In the first case, the following types of morphological changes in the auditory system are distinguished, depending on their prevalence and localization:

Absence inner ear and sometimes the rocky part temporal bone with normally developed outer and middle ears;

Various underdevelopment of the bony and membranous parts of the labyrinth (the number of cochlear curls is reduced, the vestibular labyrinth is underdeveloped, the sac is expanded), is noted with dominant deafness;

Underdevelopment of the sensory structures of the cochlea;

Degenerative disorders in the cells of the spiral ganglion and fibers of the cochlear nerve.

The second category of hereditary deafness is observed in many hereditary diseases caused by diseases of the outer layers of the body, bone, nervous, endocrine systems, diseases of internal organs.

Even with leopard syndrome (the appearance of freckles immediately after birth), there may be deafness.

Some inherited hearing defects are progressive. Sometimes they are combined with other defects: impaired vision, intelligence, kidney disease, musculoskeletal system, skin, and other disorders. Hereditary disorders of the inner ear often develop in conjunction with anomalies of the outer and middle ear.

Currently, I distinguish over 60 types of hereditary deafness with damage to the inner ear. All of them can be grouped as follows:

Michel's type (absence of a labyrinth or part of the pyramid of the eastern bone with normal development of the outer and middle ear);

Type Mondini, Shaibe, Alexander (various defects in the development of the labyrinth);

Degenerative changes in the cells of the spiral node and fibers of the cochlear nerve, which are manifested in adulthood.

Alport syndrome: the appearance of red blood cells, leukocytes and protein in the urine.

Alstrom's syndrome: a severe hereditary disorder inherited in an autosomal recessive manner.

Cockayne's syndrome: an inherited disorder transmitted in an autosomal recessive manner. After two years, there is a lag in mental and physical development.

1. Congenital disorders

With endo- or exogenous pathological effects on the organ of hearing of the fetus at the time of childbirth or during the neonatal period, in the absence of a hereditary burdened background, deafness or hearing loss, which are called congenital, may occur. Congenital disorders of the auditory function are common and manifest themselves in the pathology of both sound perception and sound conduction, more often they have the character of sensorineural hearing loss.

Among the reasons affecting the auditory function of the fetus, the most common are toxicosis in the 1st and 2nd half of pregnancy and intrauterine infections: especially rubella, transferred by the mother in the 1st trimester of pregnancy. And also: measles, flu, viral hepatitis, chicken pox, epidemic paratitis, cytomegaly, toxoplasmosis, congenital syphilis, etc.

An important role in the occurrence of hearing impairment is played by kernicterus of newborns, caused by the conflict between the mother and the child over the Rh factor or blood group. The auditory nerves are thought to be particularly susceptible to bilirubin toxicity, which occurs in neonatal kernicterus.

An increase in the frequency of hearing impairment in premature babies has been proven, especially with incompatibility of the blood of the mother and the fetus by the Rh factor and group incompatibility of blood in the presence of hearing defects in the pedigree of these children, with a combination of prematurity with various congenital malformations nervous system and other organs.

Hearing impairment can also occur with alcoholism of the mother.

1. Acquired violations

Acquired disorders occur with a wide variety of causal, the most severe with damage to the sound-receiving apparatus (inner ear, auditory nerve).

Among the causes of hearing impairment in children, the first place is occupied by the consequences of acute, otitis media. Hearing loss is one of the main symptoms of chronic suppurative otitis media. A common reason Hearing loss are diseases of the nose and nasopharynx and associated obstruction of the auditory tube (adenoids).

After birth, hearing defects can occur due to various infections:

Respiratory diseases;

Influenza; measles; scarlotina, miningitis, epidemic paratitis (mumps);

Complicated inflammation of the middle ear or causing symptoms of toxic neuritis of the auditory nerves.

A significant place in the genesis of hearing loss with minengitis is given to the violation of the protective properties of the hemetocephalic and hematolabyrinthine barriers.

With epidemic paraitis, unilateral deafness develops rapidly, combined with unilateral loss of vestibular excitability. With the flu, the degree of hearing change can vary - from complete sudden deafness in one ear, to a gradual slow decline to complete deafness at various times after the illness.

In infectious hepatitis, hearing impairment is associated with a change in the permeability of the vascular walls due to intoxication as a result of the weakening of the detoxifying function of the liver.

There are two forms of hearing impairment, depending on the dynamics of the process:

Fast, sharp;

Slow, chronic.

1. Classification of permanent hearing impairment

From a purely medical point of view. especially important criteria for classification are:

Causes of hearing impairment;

Localization of the process;

The course of the pathological process.

From the psychological and pedagogical tz. the criteria that are based on factors that have a significant impact on the development of the child's speech come to the fore:

The degree of hearing impairment;

Time of onset of hearing impairment (from birth or after speech formation);

The nature of the onset of the violation (sudden, gradual).

Currently, the criterion for distinguishing between the two main categories of hearing impairment - deafness and hearing loss - is the different degree of hearing loss.

Deafness - persistent hearing loss, in which independent mastery of speech and legible perception of someone else's speech is impossible, even at the closest distance from the ear. At the same time, the remnants of hearing are preserved, allowing to perceive loud non-speech sounds and some speech sounds at close range. This is not only a hearing loss of more than 80 dB, but also a loss or decrease in hearing at different frequencies, especially speech.

Hearing loss - persistent hearing loss, in which residual accumulation of the minimum speech reserve is possible on the basis of the remaining hearing remnants, the perception of addressed speech, at least at the closest distance from the auricle. Hearing loss less than 80 dB.

1. Hearing loss classification

All classifications of hearing loss used in practice are based on the principle of determining hearing acuity by a quantitative method (tables No. 8-9-10-11)

1.7. Deafness classification

Group 1 - children who perceive only the lowest frequencies (128-256Hz);

Group 2 - children who perceive low frequencies (up to 512Hz);

Group 3 - children receiving low and medium frequencies (up to 1-0.24 Hz);

Group 4 - children who perceive a wide frequency range (up to 2-0.48 Hz and above)

Thus, with the expansion of the frequency volume of hearing, the ability to distinguish between voice and speech sounds clearly increases, and in the presence of only low frequencies (groups 1 and 2), the ability to distinguish speech sounds is practically absent.

1. Pedagogical classification of children with hearing impairment

Developed by L.M.Boskis. It is based on the principle of speech development. She singled out two groups of children in the category of deaf and hard of hearing. Among the deaf:

1. deaf without speech (deaf and dumb);
2. deaf, retained speech (late deaf);

harm to the hearing impaired:

1. hearing impaired, having developed speech with small flaws(deviation in grammar, mistakes in writing and pronunciation);
2. hearing impaired with deep speech underdevelopment (use of individual words, short phrases with incorrect construction)

The level of speech development depends on the degree of hearing loss, the time of damage to the auditory function, the conditions in which the child is before school, and individual characteristics.

According to Boskis' observations, the following periods can be distinguished:

1. hearing loss up to 1.5-2 years, i.e. before the period of speech formation, leads to a complete absence of speech (the conditional period of speech formation is determined by the age from 2 to 7 years);
2. hearing loss from 3 to 3 years, entails the loss of the speech that has already been formed when the child's hearing corresponded to the norm;
3. hearing loss at 4-5 years of age leads to almost complete loss of speech, if measures are not taken to preserve it;
4. hearing loss by the age of 7, when speech formation has basically ended, increases the likelihood of its preservation;
5. hearing loss after 7 years, when children have already mastered literacy, can create conditions for the preservation of speech, with systematic work on it.

The conditions for raising a child before school have a significant impact on speech development. The earlier qualified assistance is provided to a child in mastering speech, the more successful its formation is. Children visiting special institutions: nurseries, kindergartens, groups at laboratories for the development of hearing and speech, etc.

And also the purposeful work of parents with them contributes to the further successful development of the speech of children at school.

Thus, the level of speech development is one of the leading criteria for attributing children with hearing impairment to the appropriate groups.

I have limited opportunities for auditory imitation, young children show a tendency to visual-muscular imitation, speech movements, which they see in others.

From all that has been said, it follows that deafness entails such severe consequences for oral speech and its development in a child (although there is no damage to the speech apparatus) that without special pedagogical intervention they turn out to be insurmountable.

1. Prevention of hearing impairment in children

Persistent hearing impairment in children is the result of previous diseases or hereditary defects of the hearing organ. Treatment activities in most cases they turn out to be ineffective. Psychological, medical and pedagogical correction and rehabilitation, as well as hearing aids give certain results, but do not fully compensate for the hearing impairment. Therefore, clinicians and teachers of deafness believe that measures are needed to prevent and eliminate factors leading to hearing loss and deafness.

Thus, hearing impairment is preventable, and elimination of their causes would lead to a significant decrease in children with hearing loss and deafness. According to the WHO, in half of the cases, hearing loss could have been prevented by the simplest means (table No. 12-13-14)

The first years of a child's life are in many aspects critical for the development of speech, which makes hearing impairment of primary importance. Untimely detection of hearing impairments in children of the first year of life leads to the development of deaf-dumbness and, as a consequence, to the disability of children.

The neonatologist of the maternity hospital of the Department of Pathology of Newborns and Nursing of Prematures on the basis of the presence of at least one of the risk factors for hearing loss and deafness in the newborn's exchange card notes the threatened hearing loss and indicates the factor. In addition, the neonatologist, upon discharge from the hospital, conducts a conversation with the parents, guiding them to examine the child for examination of the child during the first year of life, and sick and premature babies - after discharge from the hospital.

If hearing loss is suspected, the child is referred for an audiological examination at a deafness center.

In this regard, it is highly desirable to conduct behavioral screening in all children in the first year of life.

As a rule, children with unilateral and weak hearing loss are not registered in audiologopidic rooms. However, these children are at risk and require systematic observation.

Therefore, it is absolutely necessary to introduce early (from the first months of life) detection, rehabilitation of hearing impairments in children with bilateral and unilateral hearing loss, with sensorineural, mixed and conductive hearing loss, as well as not only with severe hearing loss and deafness, but also with weak and moderate.

More than 50% of cases of congenital sensorineural hearing loss and deafness have a genetic (hereditary) cause. In this case, hearing impairment may be absent immediately at birth, and develop later, affect one or both ears, vary from minor losses to deafness.

Genetic hearing impairments can be progressive, congenital, and first appear in adulthood; be a part of syndromes and be non-syndromic; with autosomal recessive and dominant inheritance, X-linked.

Every year, more and more mutations are identified that lead to sensorineural hearing impairments. Now more than 100 such disorders are known, causing changes in the structure of proteins that make up almost all elements of the inner ear: hair cells, supporting cells, vascular stria, basilar membrane, spiral node, auditory nerve.

Most of the genetically determined sensorineural hearing impairments (SNH) are autosomal recessive and non-syndromic. More than 50% of non-syndromic CHF are associated with abnormalities in the structure of the connexin 26 and connexin 30 proteins.

A child's hearing loss should be suspected if the child's development does not meet the following points:
Newborn - 3 months

• reacts to loud sounds
• wakes up from sounds
• blinks or widens his eyes in response to loud noises

3-4 months

• calms down at the voice of the mother
• stops playing if he hears new sounds
• looking for a source of new sounds that are not in sight

6-9 months

• playing with musical toys
• says "mom"

12-15 months

• knows his name and the word "no"
• actively uses a 3-5 word dictionary
• imitates some sounds

18-24 months

• knows body parts
• uses an active dictionary with 2-word phrases (at least 20-50 words)
• 50% of the child's speech is understandable to strangers

For 36 months

• using an active vocabulary of 4 sentences with 5 words (approximately 500 words)
• 80% of a child's speech is understandable to strangers
• understands some verbs

Syndromic, autosomal dominant

1. Waarderburg syndrome is the most common autosomal dominant syndrome. Characterized following symptoms: telecant, wide protruding nose bridge, fused eyebrows, iris heterochromia, sensorineural deafness, white strand of hair above the forehead, depigmented spots on the skin. In some cases, ptosis is noted, lower jaw, cleft palate or high palate, minor skeletal deformities and heart defects.
2. Branchio-otorenal syndrome (BOR-syndrome) - is characterized by anomalies in the development of the outer ear, neck cysts, hearing impairment, abnormalities in the development of the kidneys. It is believed that this syndrome accounts for 2% of severe congenital hearing impairment. The prevalence is approximately 1 in 40,000 population. All signs of the syndrome have varying expressiveness. This means that the very presence clinical manifestations and their severity may differ from patient to patient, including within the same family.
3. Type 2 neurofibromatosis - bilateral auditory nerve neuromas. The frequency is 1 per 50,000 population.
4. Stickler syndrome (David-Stickler, Stickler-Wagner) is a group of hereditary collagenopathies (II and IX types of collagen). The disease is characterized by facial changes, eye damage, hearing loss and joint abnormalities. Flattening of the face can be considered one of the typical manifestations. This is due to the underdevelopment of the zygomatic arches and bones that form the bridge of the nose. Changes of the type of the Robin complex are typical: macroglossia, micrognathia, cleavage of the hard palate. Changes in the shape of the eye lead to severe myopia. In addition, there is a predisposition to the development of glaucoma and retinal detachment. There is a pronounced hypermobility of the joints, pain, arthritis. Curvature of the spine (kyphosis, kyphoscoliosis) is typical. In addition, changes in the facial skeleton, in particular cleavage of the hard palate.
5. Achondroplasia is a hereditary human disease known since antiquity, manifested in a violation of the processes of enchondral ossification against the background of normal epostal and periosteal ossification, which leads to dwarfism due to the underdevelopment of long bones; characterized by the presence of congenital anomalies, in particular, congenital stenosis of the spinal canal.
6. Paget's disease is a hereditary disease characterized by deformation of the femur and tibia, spine and skull with severe hyperostosis, thickening and curvature of bones, and an increased incidence of tumors.

Syndromic, autosomal recessive

1. Usher's Syndrome - characterized by hearing loss, progressive vision loss, vestibular dysfunction and is in most cases the cause of deafness and blindness in school-aged children.
2. Pendred's syndrome - characterized by a violation of the biosynthesis of thyroid hormones and manifested by congenital hypothyroidism, nodular goiter and CHN.
3. Jervell-Lange-Nielsen syndrome is a rare hereditary disease that manifests itself as congenital deafness and multiple heart pathologies. This syndrome is one of the clinical forms syndrome of the extended PQ interval.
4. Refsum disease - characterized by severe progressive CNS and retinitis pigmentosa, caused by disorders of phytanic acid metabolism.

X-linked syndromic hearing damage

1. Alport syndrome - progressive CNS, progressive glomerulonephritis, and various ophthalmic signs. Hearing loss usually does not appear until age 10.

In preparing the article, the following sources were used: