Hereditary diseases of the organ of vision. Genetic counseling for eye diseases. Types of hereditary eye diseases

Hereditary diseases of the organ of vision are a large group of genetically heterogeneous diseases with a severe course, leading to early disability.

Genetics (from the Greek “genesis” - birth, origin), promoted to the category of exact sciences, shows that heredity is due to the transmission to descendants of repeating information about all the properties of a given organism. One of the important properties of heredity is conservatism, that is, the preservation of hereditary characteristics over many generations. Molecular biology shows broad prospects for altering the hereditary nature of an organism, making it possible to introduce or remove certain genes. This area of ​​genetics is called “genetic engineering”.

Currently, the study of new approaches based on a combined study of clinical signs of the disease and their correlation with the results of genetic analysis is the basis for the development of promising methods for the prevention and treatment of a number of congenital and genetically determined diseases of the organ of vision. Intrafamilial and pronounced interpopulation clinical polymorphism of diseases of the visual-nervous system has been established, which indicates their different genetic nature.

In the monograph by Khlebnikova O.V. and Dadali E.L. “Hereditary pathology of the organ of vision”, published under the editorship of E.K. Ginter, published modern ideas about the etiology, clinical picture, diagnosis and new possibilities for the prevention of hereditary eye diseases. Based on their own data on clinical-genetic correlations, the authors developed algorithms for DNA diagnostics of the most severe forms of hereditary eye diseases, presented an atlas of the clinical forms of the latter and their index according to signs that allow practicing ophthalmologists to suggest or establish the clinical-genetic form of the disease. As a result of population-based epidemiological studies, the authors found that in different regions of the Russian Federation, hereditary etiology is detected in 30% of patients with eye diseases, and in the structure of blindness and low vision it ranges from 42 to 84% in different populations. According to A.M. Shamshinova (2001), in 42.3% of cases, eye diseases are caused by hereditary factors. In recent years, there has been a clear trend towards an increase in the share of hereditary diseases in the structure of ophthalmopathology.

For practicing ophthalmologists, identification of a genetic variant is necessary not only to determine the characteristics of clinical manifestations and the course of eye disease, but, above all, to establish the type of inheritance, calculate the risk of having a sick child in a burdened family and plan preventive measures aimed at preventing its birth. DNA diagnostic methods are more accurate than traditional ones, as they allow one to assess the genetic risk of developing eye disease in a family. To date, not enough work has been done to identify individual genetic variants using molecular genetic methods. Unfortunately, there are not enough such research centers in the country. And the existing DNA diagnostics laboratory and genetic epidemiology laboratory at the Federal State Budgetary Institution MGSC RAMS cannot cover the large contingent of those in need of these examinations.

It is important to remember the terminology related to hereditary pathology. A gene is the basic unit of heredity, embodied in the substance of heredity - deoxyribonucleic acid (DNA) and is a section of its molecule that is transmitted from parents to their descendants. The sizes of genes are not the same and depend on the size of the protein that the gene encodes. There are more than 20 thousand genes.

Epigenetics is the science of gene activity and changes; it studies everything related to DNA and affecting its structure and function. It is well known that the hereditary nature of an organism is determined by the set of genes (genome) contained in the DNA of each cell. DNA contains more than 3 billion nucleotide bases of four main types: adenine, cytosine, guanine and thymine. A large amount of DNA is stored in a relatively small volume of the cell nucleus. Each chromosome contains one strand of DNA. The sequence of bases in DNA determines human life.

The cause of hereditary diseases is damage to genes that are part of the cell - a unique biological structural unit of the body. The nucleus of each cell contains chromosomes - material carriers of human hereditary properties, containing one giant DNA molecule and hundreds of thousands of genes that control important links in metabolism at all stages of development of the human body. Therefore, the most direct approach to diagnosing hereditary diseases is to study the DNA of the corresponding genes. Modern methods of molecular genetics make it possible to specifically study almost any fragment of DNA in a human cell. A necessary condition for DNA diagnostics is the availability of information about the location of the gene on a specific chromosome. A locus is a separate section of a chromosome responsible for the implementation of a certain hereditary trait.

Genome - a set of chromosomes containing units of heredity. Therefore, the hereditary nature of an organism is determined by the genome contained in the DNA of each cell. Through mapping, it is possible to identify the position of each gene on a chromosome relative to other genes.

The gene creates enzymes that regulate biochemical processes and ensures the life of the cell. DNA methylation is an important biochemical pathway, the disruption of which leads to the development of eye diseases. As a result of complex biochemical changes in the body under the influence of many reasons (diseases, intoxication, environmental influences, low and high temperatures, ionizing radiation, etc.), changes in the structure of chromosomes and genes - mutations - can occur. A mutation in a human somatic or germ cell can lead to the development of a hereditary disease: corneal dystrophy, hereditary cataract, congenital glaucoma, retinal abiotrophy and many others.

The most important problem in counseling practice is determining the type of inheritance of the disease. Three main types of inheritance have been proven: 1) autosomal recessive type - both parents are carriers of a defective gene, the pathological gene is transmitted from generation to generation, the incidence of the disease is the same in men and women (example: cystic fibrosis); 2) autosomal dominant type - only one of the parents can be the carrier of the gene (example: tuberculous scleritis); 3) X-linked inheritance is characterized by the following genealogical data: a sick father can pass on a pathological gene to daughters who will be phenotypically healthy, but are carriers of a defective chromosome. A female carrier can receive a pathological gene from both mother and father and passes it on to her sons (example: congenital color vision deficiency).

At the Ufa Research Institute of Eye Diseases, together with the Institute of Biochemistry and Genetics of the Ufa Scientific Center of the Russian Academy of Sciences, molecular genetic studies of certain hereditary diseases of the organ of vision have been carried out for many years.

For the first time in the Republic of Bashkortostan, the effectiveness of predicting congenital hereditary cataracts was studied, taking into account genetic factors and its surgical treatment. The linkage of the autosomal dominant congenital cataract gene with highly polymorphic microsatellite markers located within the β-crystallin gene cluster was analyzed. Genotyping of individuals in the studied pedigrees was carried out using marker loci and the genetic heterogeneity of autosomal dominant congenital cataract was studied. The possibility of prenatal diagnosis of congenital hereditary cataract has been proven based on the established linkage of the ADVC gene with microsatellite markers D22S264, TOP1P2, CRYBB2 in the region of the β-crystallin gene cluster. The lack of linkage between autosomal dominant congenital cataract and the above markers in a number of other families with this pathology indicates its genetic heterogeneity.

In the children's department of the institute, genetic research was carried out on the problem of pigmentary abiotrophy (Greek bios - life, trophe - nutrition) of the retina in adults and children. Tapeto-retinal abiotrophies in children are among the poorly studied severe hereditary progressive diseases that lead to blindness at working age. The disease is inherited in an autosomal recessive manner. Based on the type of inheritance, there are monogenic (caused by defects in one gene) and digenic (caused by defects in two genes) retinal pigment abiotrophy.

The recurrence of this pathology in families of 3-4 generations has been revealed, more often manifesting itself in children with close relationships between their parents. Several clinical forms of retinitis pigmentosa have been identified. The degree of development of retinal pigmentation depends on the genetic type of retinitis pigmentosa and the age of the patient. Various periods of manifestation of new signs of the disease have been noted - from 8-10 years to 40-55 years. When the disease occurs, disturbances in dark adaptation, concentric narrowing of visual fields, and night blindness are noted. Various forms of hereditary retinal degeneration are caused by mutations in the rhodopsin gene. Perinatal diagnosis is aided by molecular biological genotyping, which allows the identification of a large number of genes causing this disease. However, at present, interaction between practicing ophthalmologists and specialists in the field of molecular genetics is not always carried out.

The institute conducted research on hereditary open-angle glaucoma. Based on a clinical, genealogical and molecular genetic study of members of 138 families, it was found that in patients with a family history, the predominant clinical form of primary open-angle glaucoma is pseudoexfoliation glaucoma (56.8%), and in the group without a family history - pigmentary glaucoma (45.5%). %). A clinical and genealogical study of families in which primary open-angle glaucoma was confirmed in several generations revealed similarities in the clinical manifestations of the disease, and the phenomenon of anticipation was traced. As a result of molecular genetic analysis, it was found that the frequency of the Q368X mutation of the myocilin gene in the group with a family history of the disease is 1.35%, which indicates the advisability of testing it in individuals with a family history of the disease. Therefore, if there is a family history of primary open-angle glaucoma, premorbid diagnosis of it in blood relatives is necessary.

A comparison was made of single-digit indicators between husband and wife, parents and children. A higher correlation coefficient between parents and offspring compared to those between spouses indicated the great importance of genotypic factors in determining traits. Summarizing hereditary traits and microfeatures, identifying patterns of their impact on the development of glaucoma in representatives of a specific pedigree made it possible to timely diagnose the disease or predisposition to it. Tests for susceptibility to glaucoma, as noted by R.P. Shikunova, help to predict the disease long before its clinical manifestations and contribute to the correct prediction of pathology in future generations.

To date, the clinical and genetic characteristics of 20 nosological forms of hereditary corneal dystrophies, represented by 35 genetic variants, have been well studied. Autosomal dominant, autosomal recessive and X-linked recessive types of inheritance of NDD have been described. Hereditary diseases of the cornea are represented by dystrophies of various layers of the cornea and ectasia. In recent years, cases of keratoconus have become more frequent, most of which are sporadic. Only in 6-8% of cases is the monogenic nature of the disease established. Five genetic variants of keratoconus, clinically indistinguishable, have been described, and the keratoconus gene has been mapped on the chromosome. Research at the institute on the problem of inheritance of keratoconus continues.

Thus, identification of a pathological gene and its mutations forms the basis for understanding the pathogenesis of the disease, predicting the course of the process and finding ways for effective therapy. Considering the existence of a wide nosological spectrum and pronounced genetic heterogeneity of hereditary diseases of the organ of vision, systematic work is needed to determine the algorithm for clinical genetic research in affected families.

Eyes are one of the most important organs for humans, connected to the brain and other organs. Based on the information provided by the eyes, a person performs certain actions, orients himself in space, and forms the perception of actions and objects.

Some people, due to heredity, cannot use their vision to the fullest. Congenital eye abnormalities occur in 1–2% of all newborns. Modern medicine has found more than 1,200 genes responsible for the possibility of certain diseases.

Many of the hereditary eye diseases are asymptomatic and do not change visual acuity, so a person who lives for a long time may not notice some small changes, and thereby loses precious time.

Types of hereditary eye diseases

Ophthalmologists divide hereditary diseases into 3 groups:

Among the eye diseases that are inherited or that occur at the initial stage of fetal development are:

Glaucoma

Glaucoma– a severe chronic eye disease characterized by increased intraocular pressure (IOP). In this case, the optic nerve is affected, vision decreases and complete blindness may occur. The optic nerve is completely destroyed, and blindness is irreversible.

Unfortunately, glaucoma is quite common, affecting people over the age of forty. According to WHO, the number of glaucoma patients in the world reaches 100 million people. At a younger age, glaucoma is much less common.

Intraocular pressure increases for two main reasons: the formation of intraocular fluid in excessive quantities and a violation of the removal of intraocular fluid by the drainage system of the eye. Retention of intraocular fluid causes an increase in IOP, and high IOP leads to optic nerve death and blindness. However, what causes excessive fluid formation is still unknown. It is believed that hereditary factors play a huge role in the occurrence of glaucoma. If you have relatives in your family who have glaucoma, you should be examined by an ophthalmologist at least once a year.

Neglecting treatment for glaucoma inevitably leads to blindness.

There are several types of glaucoma:

Congenital glaucoma. which can be caused by genetic causes or diseases and injuries of the fetus during periods of embryonic development or childbirth. Congenital glaucoma manifests itself in the first weeks of life. The disease is quite rare - there is only 1 case of glaucoma per 10-20 thousand newborns.

The cause of the disease is most often autosomal recessive heredity. In this case, abnormalities of the eyeball are observed. The reasons may also be the effects on the fetus of diseases such as measles. rubella . flu . toxoplasmosis . mumps . hypoxia .

Juvenile or juvenile glaucoma. Develops in children after three years of age and young people up to 35 years of age. The causes of the disease are congenital changes in the iris of the eye.

Secondary glaucoma- this is a consequence of other eye or general diseases that affect the ocular structures responsible for the circulation and outflow of intraocular fluid from the eye. Mechanical damage to the eye may also be the cause.

Primary adult glaucoma– the most common type of chronic glaucoma, which is associated with age-related eye changes. The disease is divided into 4 main clinical forms: open angle glaucoma. mixed glaucoma. closed-angle glaucoma And glaucoma with normal IOP .

Symptoms of glaucoma

Symptoms of glaucoma directly depend on the form and stage of development of the disease. Its insidiousness is that at the initial stage of the disease, 80% of patients do not experience any inconvenience. What you should be concerned about:

Congenital glaucoma in children is manifested by stretching of the cornea, which is elastic in newborns and returns to normal size after the first week of life. With glaucoma, the eyes appear more expressive and larger than normal. This leads to stretching and thinning of the retina and its further detachment with breaks.

Observed myopia or myopic astigmatism . a slight increase in intraocular pressure in the early stages of the disease. Swelling of the cornea occurs, which leads to deterioration of vision, and in the future it is associated with atrophy of the optic nerve and deformation of the fundus.

The main goal in the treatment of glaucoma is to preserve visual function with minimal side effects from the therapy used and maintain the patient’s normal quality of life. The key to successful treatment is the patient’s correct understanding of the serious prognosis of the disease and the need for adequate treatment.

Glaucoma is treated conservative(medicine) method, laser And surgical way. Drug treatment, in turn, is carried out in three directions: ophthalmic-hypotensive therapy - measures aimed at reducing intraocular pressure. Measures aimed at improving blood supply to the inner eye membranes and the intraocular part of the optic nerve. Normalization of metabolism (metabolic processes) in ocular tissues to influence degenerative processes that are characteristic of glaucoma. The symptoms of glaucoma and its complications are relieved.

Previously, pilocarpine, a drug that narrows the pupil of the eye, was used to treat glaucoma with drugs. Now it has been replaced by new drugs: Betoptik . Betadine . Timolol . Trusopt . Xalatan and a number of others. The newest drugs allow a more targeted effect on glaucoma: reducing fluid production and improving its outflow.

Laser treatment became possible not so long ago, after the creation of modern ophthalmic laser units with a certain set of parameters that affect the structures of the eyeball. This has made it possible to develop and apply a variety of laser treatment methods for glaucoma.

Laser treatment of glaucoma has a number of advantages: firstly, the low invasiveness of the procedure, secondly, the complete absence of serious complications that may arise in the postoperative period, thirdly, the possibility of carrying out treatment on an outpatient basis, which significantly affects the savings, the possibility of , if necessary, repeated laser interventions, with a significant decrease in the hypotensive effect in the postoperative period.

Laser treatment of glaucoma carried out using the following methods:

Surgical treatment consists of creating an alternative system for the outflow of intraocular fluid, after which intraocular pressure is normalized without the use of medications.

Different forms and types of glaucoma require different surgical interventions and are resolved individually each time. The exception is congenital glaucoma in children; this form of the disease can only be treated with surgical methods.

Prevention of glaucoma

Glaucoma is perhaps the most common cause of blindness and therefore preventing the progression of the disease is of great socio-economic importance both for the individual and for society as a whole.

The course of the disease largely depends on the lifestyle of the patient; treatment of glaucoma cannot be successful without lifestyle correction. Physical and nervous overload should be avoided, especially in older age. The permissible maximum weight for lifting should not exceed 10 kg. You should also not read in poor lighting or for long periods of time.

Diet is also of great importance; you need to eat rationally, according to your age. Preference should be given to vegetable dishes, fish, raw vegetables and fruits and limit the intake of animal fats and sugar. Nicotine is very harmful to the eyes, therefore, it is better to quit smoking, the sooner the better.

The most effective way to prevent glaucoma is a systematic examination by an ophthalmologist and monitoring of intraocular pressure for people over 40-45 years of age. You need to visit a doctor at least once a year. People who have relatives with glaucoma should be especially attentive to the issues of glaucoma prevention.

If the first symptoms of glaucoma appear, you should immediately consult a doctor. If any form of glaucoma is detected, it is necessary to undergo medical observation by an ophthalmologist. Remember that currently medicine does not have the ability to restore vision lost as a result of the progression of glaucoma.

Congenital glaucoma

Congenital glaucoma

Congenital glaucoma is a genetic, less commonly, acquired in utero disease, which is characterized by underdevelopment of the anterior chamber angle and trabecular meshwork, which ultimately leads to increased intraocular pressure. This condition is considered relatively rare in ophthalmology and occurs in approximately one case per 10,000 births. Some researchers believe that these statistics do not accurately reflect reality, because some forms of congenital glaucoma may not manifest themselves until adolescence. Despite the fact that the pathology is inherited by an autosomal recessive mechanism, boys are somewhat prevalent among patients - the gender distribution is approximately 3:2. Based on the age of development of the main symptoms, as well as the presence or absence of genetic defects, several clinical forms of this disease are distinguished. The importance of timely detection of congenital glaucoma is due to the fact that without treatment, a child may become blind 4-5 years after the development of the first manifestations of the pathology.

Causes of congenital glaucoma

The vast majority of cases of congenital glaucoma (at least 80%) are accompanied by a mutation of the CYP1B1 gene, which is localized on the 2nd chromosome. It encodes the cytochrome P4501B1 protein, the functions of which have not been sufficiently studied to date. It is assumed that this protein is somehow involved in the synthesis and destruction of signaling molecules that take part in the formation of the trabecular network of the anterior chamber of the eye. Defects in the structure of cytochrome P4501B1 lead to the fact that the metabolism of the above compounds becomes abnormal, which contributes to impaired eye formation and the development of congenital glaucoma. More than fifty types of CYP1B1 gene mutations are now known that are reliably associated with the development of this disease, but it has not yet been possible to identify the relationship between specific gene defects and certain clinical forms.

In addition, there are indications of the role of another gene, MYOC, located on chromosome 1, in the development of congenital glaucoma. The product of its expression, a protein called myocillin, is widely represented in ocular tissues and is also involved in the formation and functioning of the trabecular meshwork of the eye. Mutations in this gene were previously known to cause juvenile open-angle glaucoma. however, when MYOC and CYP1B1 are simultaneously damaged, a congenital version of this pathology develops. Some researchers in the field of genetics believe that the discovery of a mutation in the myocillin gene in the presence of a CYP1B1 defect does not play a special clinical role in the development of congenital glaucoma and is simply a coincidence. Mutations in both these genes are inherited in an autosomal recessive manner.

In addition to hereditary forms of this pathology, congenital glaucoma is diagnosed in approximately 20% of cases in the absence of both cases of the disease and pathological genes in the parents. In this case, the cause of the development of eye disorders can be either spontaneous mutations or damage to eye tissue in the prenatal period. The latter may be caused by infection of the mother during pregnancy with certain infections (for example, toxoplasmosis, rubella), intrauterine injuries to the fetus, and retinoblastoma. exposure to teratogenic factors. Since in this situation there is no genetic defect, this pathology is called secondary congenital glaucoma. In addition, similar visual impairments can occur with some other congenital diseases (Marfan syndrome, anhidrosis and others).

Whatever the cause of congenital glaucoma, the mechanism of development of disorders in this condition is almost the same. Due to underdevelopment of the angle of the anterior chamber of the eye and the trabecular meshwork, aqueous humor cannot leave the cavity normally; it accumulates, which is accompanied by a gradual increase in intraocular pressure. A feature of congenital glaucoma is the fact that the tissues of the sclera and cornea in children have greater elasticity than in adults, therefore, when moisture accumulates, the size of the eyeball increases (usually two at once, very rarely only one). This slightly reduces intraocular pressure, but over time this mechanism also becomes insufficient. The lens and cornea become flattened, and microtears may appear on the latter, leading to clouding; The optic disc is damaged and the retina becomes thinner. Ultimately, its detachment may occur - corneal clouding and retinal detachment are the leading causes of blindness in congenital glaucoma.

Classification of congenital glaucoma

In clinical practice, congenital glaucoma is primarily divided into three types - primary, secondary and combined. Primary is caused by genetic disorders, is inherited by an autosomal recessive mechanism and accounts for about 80% of all cases of the disease. The cause of secondary congenital glaucoma is an intrauterine disorder in the formation of the visual organs of various non-genetic nature. The combined type, as the name suggests, is accompanied by the presence of congenital glaucoma against the background of other hereditary diseases and conditions. The primary form, caused by genetic defects, is in turn divided into three clinical forms:

1. Early congenital glaucoma - in this form, signs of the disease are detected at birth, or they appear in the first three years of the child’s life.
2. Infantile congenital glaucoma develops at the age of 3-10 years, its clinical course is no longer similar to the early type and approaches that of adults with other forms of glaucoma.
3. Juvenile congenital glaucoma - the first manifestations of this form of the disease are most often recorded in adolescence, the symptoms are very similar to the infantile type of pathology.

Such a significant difference in the age of development of congenital glaucoma is directly related to the degree of underdevelopment of the trabecular network of the eye. The more pronounced the disturbances in these structures, the earlier the accumulation of aqueous humor begins with an increase in intraocular pressure. If the underdevelopment of the angle of the anterior chamber of the eye does not reach significant values, then in the first years of the child’s life the outflow occurs quite normally, and disorders develop much later. Attempts to associate certain clinical forms of congenital glaucoma with specific types of CYP1B1 gene mutations have not been successful to date, and the mechanisms of development of one or another type of disease are still unknown.

Symptoms of congenital glaucoma

The most peculiar manifestations are characterized by the early form of primary congenital glaucoma, which is due to the anatomical features of the structure of the eye in a child under 3 years of age. In very rare cases, glaucoma changes can be noticed already at birth; most often, in the first 2-3 months of life, the disease does not manifest itself in any way. Then the child becomes restless, sleeps poorly, and is very often capricious - this is due to the unpleasant and painful sensations with which congenital glaucoma begins. After a few weeks or months, a slow increase in the size of the eyeballs (less often one) begins. Increased intraocular pressure and elasticity of the scleral tissue can lead to a significant enlargement of the eyes, which externally creates a false impression of a beautiful “big-eyed” child. Then these symptoms are accompanied by swelling, photophobia, lacrimation, and sometimes clouding of the cornea occurs.

Infantile and juvenile forms of congenital glaucoma are very similar in many respects, only the age of development of the first manifestations of the disease differs. In this case, as a rule, an increase in the size of the eyeballs does not occur; the pathology begins with a feeling of discomfort and pain in the eyes, headaches. The child may complain of deteriorating vision (the appearance of bright halos around light sources, “midges” in front of the eyes). These types of congenital glaucoma are often accompanied by other visual disorders - strabismus. astigmatism. myopia. Over time, the field of vision narrows (the ability to see objects with peripheral vision is lost), and dark adaptation is disrupted. Photophobia, swelling and injection of scleral vessels, characteristic of the early form of the disease, are most often not observed in these forms. If left untreated, any type of congenital glaucoma eventually leads to blindness due to retinal detachment or optic nerve atrophy.

Diagnosis of congenital glaucoma

Congenital glaucoma is identified by an ophthalmologist based on examination data and ophthalmological studies (tonometry, gonioscopy, keratometry, biomicroscopy, ophthalmoscopy, ultrasound biometry). Also, an important role in the diagnosis of this condition is played by genetic studies, the study of hereditary history and the course of pregnancy. Upon examination, enlarged (in the early form) or normal size of the eyes are detected; swelling of the tissues surrounding the eyeball may also be observed. The horizontal diameter of the cornea is increased, micro-tears and clouding are possible on it, the sclera is thinned and has a bluish tint, the iris is also affected in congenital glaucoma - atrophic processes occur in it, the pupil reacts sluggishly to light stimuli. The anterior chamber of the eye is deepened (1.5-2 times more than the age norm).

No pathological changes occur in the fundus for a long time, since due to the increase in the size of the eyeball, intraocular pressure initially does not reach significant values. But then excavation of the optic disc develops quite quickly, however, as the pressure decreases, the severity of this phenomenon also decreases. Due to the increase in eye size, congenital glaucoma causes thinning of the retina, which, if left untreated, can lead to its rupture and rhegmatogenous detachment. Often, against the background of such changes, myopia is detected. Tonometry shows a slight increase in intraocular pressure, but this indicator should be compared with the anteroposterior size of the eye, since scleral stretching smoothes out IOP values.

A study of the hereditary history can reveal similar changes in the patient’s relatives, and it is often possible to determine an autosomal recessive type of inheritance - this indicates in favor of primary congenital glaucoma. The presence of maternal infectious diseases, injuries, and exposure to teratogenic factors during pregnancy indicates the possibility of developing a secondary form of the disease. Genetic diagnosis is carried out through direct sequencing of the CYP1B1 gene sequence, which makes it possible to identify its mutations. Thus, only a geneticist can clearly prove the presence of primary congenital glaucoma. In addition, if one of the parents or their relatives has this condition, a search for the pathological form of the gene can be performed before conception or prenatal diagnosis through amniocentesis or other techniques.

Treatment and prognosis of congenital glaucoma

Treatment of congenital glaucoma is only surgical; it is possible to use modern laser technologies. Conservative therapy using traditional remedies (pilocarpine drops, clonidine, epinephrine, dorzolamide) is auxiliary and can be used for some time while waiting for surgery. Surgical intervention is reduced to the formation of a pathway for the outflow of aqueous humor, which reduces intraocular pressure and eliminates congenital glaucoma. The method and scheme of the operation is chosen in each specific case strictly individually. Depending on the clinical picture and structural features of the eyeball, goniotomy and sinustrabeculectomy can be performed. drainage operations, laser cyclophotocoagulation or cyclocryocoagulation.

The prognosis of congenital glaucoma with timely diagnosis and surgery is most often favorable, but if treatment is carried out late, visual impairment of varying severity is possible. After eliminating glaucoma, at least three months of follow-up with an ophthalmologist is necessary.

General characteristics of the disease

The medical term “glaucoma” is commonly understood as a whole group of severe ophthalmological pathologies. The disease gets its name from the Greek word “??????????”, the literal translation of which means “blue clouding of the eyes.” Such an exotic name for the disease is due to the special color of the pupil. With glaucoma, it becomes a specific blue-green color, acquires an extended immobile state and leads to complete blindness.

Signs of glaucoma can be diagnosed in a person of any age. However, glaucoma occurs most frequently in older people. So, for example, cases of congenital glaucoma are diagnosed in only one child out of 15-20 thousand children in the first months of life. In people over 75 years of age, diagnosed cases of glaucoma are already more than 3%.

Causes of glaucoma

At the moment, there is no consensus in medical scientific circles about the causes and mechanisms of the development of glaucoma. One of the versions is the theory of the influence of increased intraocular pressure.

It is believed that systematic or periodically occurring increased IOP can lead to trophic disorders in the structure of the eye, impaired fluid outflow and other complications that cause defects in the retina and optic nerve in glaucoma.

The version about the multifactorial nature of glaucoma is also quite common. The combination of factors that cause glaucoma includes hereditary causes, structural anomalies of the visual organs, trauma, pathologies of the nervous, vascular and endocrine systems.

According to this theory, the cumulative effect of all or several of the above factors can trigger the development of glaucoma.

The term “glaucoma” includes more than 60 different types of disease with specific symptoms. Glaucoma of any of these types is primarily characterized by damage to the optic nerve fibers. Over time, the process moves into the stage of complete atrophy of visual function.

The earliest symptom of glaucoma is poor drainage of intraocular fluid from the eyeball. This is followed by deterioration of the blood supply to the tissues of the eye, hypoxia and ischemia of the optic nerves. Lack of oxygen to the tissues of the eye, as one of the signs of glaucoma, leads to gradual destruction and atrophy of the visual fibers.

Some of them may be in a state of so-called parabiosis (sleep). This allows you to restore eye function if treatment for glaucoma is started in a timely manner.

Types of glaucoma

Congenital glaucoma is most often genetically determined or caused by intrauterine infections. Symptoms of this type of glaucoma appear in the first weeks of life. A child is born with high intraocular pressure, bilateral enlargement of the cornea or the entire eyeball. In common parlance, congenital glaucoma is sometimes called hydrocele or bull's eye.

Juvenile or juvenile glaucoma is diagnosed in children over 3 years of age. In late cases of manifestation of signs of glaucoma, the disease can manifest itself up to 35 years. At an older age, diagnosed glaucoma is already called adult glaucoma and can be primary or secondary.

Secondary glaucoma is usually understood as clouding of the pupil and signs of optic nerve atrophy, which have become a complication of another ophthalmological disease.

Types and stages of primary glaucoma

Primary glaucoma is the most common type of the disease. It can be closed-angle or open-angle.

Clinical symptoms of open-angle glaucoma include slow progression of the disease, the absence of any unpleasant sensations in the patient, the appearance of the rainbow circle effect in the late stage of the disease, and gradual blurred vision. Open-angle glaucoma, as a rule, affects both eyes at once, but develops asymmetrically (at a different pace in both eyes).

Angle-closure glaucoma is more often diagnosed in women, since small eye sizes are predisposing factors to this type of disease. Signs of this type of glaucoma include the presence of acute attacks of vision loss. Under the influence of nervous shock, overwork or prolonged work in an uncomfortable position during an attack, sharp blurred vision occurs, pain in the eyes, nausea, and vomiting may occur. Then the patient develops a state of preglaucoma with a period of relatively normal vision.

Depending on the severity of glaucoma, glaucoma is divided into four stages:

Diagnosis of glaucoma

The effectiveness of glaucoma treatment depends on timely diagnosis of the disease. The leading importance in it is the determination of intracranial pressure using tonometry or elastotonomery. The quality of the outflow of intraocular fluid in glaucoma is studied using electron tonography.

The perimetry method for measuring the boundaries of vision, as well as gonioscopy, are also of high value in diagnosing the disease. Using the last named method, the structures of the anterior chamber of the eye are examined. The use of scanning laser ophthalmoscopy allows us to identify qualitative and quantitative disorders in the structure of the optic nerves.

Each of these methods is highly informative, therefore, only one of them can be used in dynamic monitoring of the effectiveness of glaucoma treatment.

Glaucoma treatment

Treatment for glaucoma can be medication or surgery. Operations for glaucoma, in turn, are also of two types: traditional, performed using a microsurgical scalpel, or laser.

The basis for drug treatment of glaucoma consists of three areas:

Ophthalmic hypotensive therapy (lowering IOP) plays a leading role in the drug treatment of glaucoma. The other two areas are of an auxiliary nature. For example, they use a natural herbal complex from Dr. Pankov to treat diseases of the organs of vision.

The use of conservative treatment of glaucoma is indicated only in the early stages of the disease. For grade III-IV glaucoma and the ineffectiveness of drug therapy in relieving an acute attack, surgery is recommended.

Laser surgery for glaucoma eliminates obstacles to the outflow of intraocular fluid. The technique of laser surgery for glaucoma involves the use of iridectomy or trabeculoplasty. Their essence is to create a micro-explosion for local tissue rupture or to cause a burn with subsequent scarring.

The advantages of laser surgery for glaucoma include a short rehabilitation period, outpatient conditions and local anesthesia during the application of the technique. The main disadvantage of laser surgery for glaucoma is the limited effect. At the stage of mature glaucoma, only radical surgery is used.

The disease is treated surgically using several types of techniques:

There is no single standard for the use of one or another type of surgery for glaucoma. In each specific case, the type of surgery for glaucoma is selected individually.

Traditional treatment of glaucoma

The prevalence of the disease has led to the emergence of a huge number of methods of traditional treatment of glaucoma. Some of them, for example, therapeutic nutrition, the use of sunglasses, breathing exercises, and aerial procedures are welcomed by official medicine.

However, it must also be recognized that many methods of treating glaucoma with folk remedies are viewed with skepticism by official medicine: be it infusions of duckweed, woodlice, lotions with aloe juice, dripping honey into the eyes, etc.

Patients and families contact for genetic counseling to obtain information about the nature of the disease, the risk of developing the disease or transmitting it to children, about the problems of genetic testing, childbirth and treatment. Genetic counseling aims to help patients understand the information received, choose the best course of action and best adapt to the disease.

Accurate diagnostics- the main condition for effective genetic counseling. Diagnosis of many hereditary eye diseases is based on clinical data, this requires the participation of clinical specialists and, often, a multidisciplinary approach, including genetic, ophthalmological and electrophysiological studies.

Diagnosis is based on a detailed family history with the construction of a pedigree tree of three generations, examination (often of several family members), as well as on medical history, including a description of systemic manifestations. It is extremely important to be alert for ocular and extraocular manifestations of the disease.

Genetic counseling with hereditary eye diseases can be a particularly difficult task. Heterogeneity and overlap of phenotypes make diagnosis difficult for patients to understand. Many hereditary retinal diseases are accompanied by progressive deterioration of vision and require preliminary adaptation to the need for care. The communication needs of patients with visual impairments require that information be delivered to them in an appropriate format.

A) Genetic laboratory tests. Molecular analysis has become cheaper and more accessible, and is now widely used in the clinic. The clinician needs to be aware of its capabilities. For monogenic inherited eye diseases, the analysis will likely involve gene sequencing. Tests are performed as a complement to a detailed clinical examination. They are carried out to clarify the diagnosis, for example, in diseases characterized by extreme genetic heterogeneity that are clinically indistinguishable.

In future genetic diagnostics may be required for gene-specific treatment (drug or gene therapy). If assessing the risk, for example, in a disease with dominant inheritance, is not difficult, then for relatives of a patient with a dominant phenotype with reduced penetrance (dominant optic atrophy and autosomal dominant congenital cataracts) or children of women from a family where men suffer from X-linked With retinoschisis it is more complex.

Molecular analysis performed based on DNA material, isolated from the peripheral blood or saliva of one sick patient (proband) or a wider circle of relatives. Once a pathogenic mutation is identified, other family members can be screened, incl. unborn, for its presence.

b) What is a mutation? Genetic variability results from the process of DNA mutation. Various mechanisms of mutations in human hereditary genetic and mendelian diseases have been described. Most of them represent an all-or-nothing phenomenon: sick patients are carriers of pathogenic genetic changes ("mutations"), while healthy individuals are not. In such cases, sick representatives of this family are carriers of the same genetic changes, and these changes do not change.

However, there is a small group of diseases, which include, for example, myotonic dystrophy, characterized by “dynamic” mutations, in which genetic changes in different generations of the same family can vary.

1. Chromosomal alterations. The most gross genetic changes are alterations at the chromosome level, namely cytogenetically visualized rearrangements such as deletions, inversions, duplications and translocations. Such a “genomic imbalance” is very poorly tolerated, and during the entire period of research, only a small part of all possible rearrangements was observed. Such changes include trisomies (eg, trisomy 21 or Down syndrome) as well as large chromosomal deletions (eg, chromosomal deletion 11p causing WAGR syndrome, see above).

2. Submicroscopic genomic rearrangements. It is now possible to compare subtle differences in DNA copy numbers between different individuals. “Submicroscopic genomic rearrangements” include both the loss of genetic material (microdeletions) and the increase in its amount (microduplications) and are the causes of hereditary human diseases. For example, submicroscopic deletions of the X chromosome have been described in choroideremia, xLRP, and Norrie disease.

3. Monogenic mutations. Many hereditary eye diseases develop as a result of pathological changes in a single gene. The best described mutations are single base substitutions, also called “point mutations.” The Cardiff Human Gene Mutation Database is an online repository of information on identified human gene mutations. Pathogenic point mutations can lead to the replacement of one encoded amino acid with another (missense mutations). If these changes cause the protein to malfunction, it leads to disease.

A change in one base that leads to to the formation of a stop codon from a codon, normally encoding any amino acid, is called a nonsense mutation. Most nonsense mutations cause a decrease in the amount of protein produced during translation.

After transcription from immature mRNA molecule During the splicing process, excess sections are cut out and mature mRNA is formed. Splicing is a complex process during which a huge protein complex (spliceosome) interacts with mRNA molecules. There are a huge number of mutations - especially those located at or near the junction between exons and nitrons - that cause interruption of the splicing process (splicing mutations).

Others often common DNA mutations, causing monogenic human diseases, are small deletions/insertions in which up to 20 base pairs of DNA are lost or inserted. Insertion/deletion mutations less than three bases in length cause a shift in the reading frame of the gene and the formation of a premature termination codon. Most of these mutations result in the formation of mRNA from which the polypeptide is not translated.

V) DNA sequencing. It is believed that in diseases transmitted according to Mendelian laws, most patients are carriers of one pathogenic DNA change (mutation). Most of these mutations are located within or near the coding sequences of genes, the list of which is growing.

1. Traditional DNA sequencing. Until recently, DNA sequencing was performed using traditional methods. This was done by amplifying short fragments of each gene (perhaps 300-500 base pairs) using polymerase chain reaction. Therefore, the process of sequencing small genes is easier and cheaper than sequencing large genes. It takes ten times longer to study ten genes of the same size than to study a single gene. This kind of work is expensive and time consuming. In some situations, the results of gene analysis determine the tactics for further patient management.

At xLRP Most patients have mutations in one of two genes (RP2 and RPGR), so the traditional sequencing method using modern technologies turns out to be quite simple and informative for practical use. This is also true for stromal corneal dystrophies caused by mutations of the TGFBI gene of chromosome 5q31, since the number of mutations causing Bowman's membrane dystrophies (Thiel-Behnke and Reis-Buckler), as well as granular and cribriform type I, is very small.

But mutation analysis may be difficult even if the disease is caused by mutations in a single gene. For example, laboratory diagnosis of Cohen's syndrome and Alström's syndrome is very difficult due to the size and complexity of the genes whose mutations cause these diseases. In the case of ABCA4 (its mutation causes Stargardt disease), which contains 51 exons and 6000-7000 base pairs of DNA, sequencing the gene becomes an incredibly time-consuming task. In addition, the sensitivity of the method for detecting mutations, including known ABCA4 mutations, is significantly less than 100%. As a result, the value of a negative result is greatly reduced.

Finally, for some genes, including ABCA4, normally there is a high degree of variability for both the gene and the encoded protein. Answering the question of whether a variation resulting in a single amino acid substitution is pathogenic remains a challenge.

2. High-throughput DNA sequencing. In genetically heterogeneous diseases (eg, congenital cataracts, neuroopticopathy, arRP, Usher syndrome), when mutations in a huge number of genes are possible and there is no predominance of mutations in any one gene, a diagnostic strategy based on traditional DNA sequencing is of little use. Some success has been achieved with the advent of DNA chips, which make it possible to identify previously described mutations (for example, Leber congenital amaurosis, Stargardt disease), but these techniques are applicable mainly to previously examined populations and their value is limited.

Massive parallel DNA sequencing, also called next-generation sequencing, may be able to change this situation. These developments make it possible to sequence the entire human genome and provide the opportunity to analyze all exons of all genes or any part of them in any patient. With the help of these technological developments, it has already been possible to significantly speed up the process of identifying unknown genes whose mutations cause human diseases. With the price falling (it is projected that sequencing the entire human genome will cost as little as $1,000 in the not-too-distant future), there is a real possibility that large-scale genetic research will become a reality.

These studies will require solutions Problems storing huge amounts of data, since such systems produce gigantic volumes of information. Moreover, since many of the abnormalities that cause human eye disease are missense disorders, and since a huge number of our genes normally have differences manifested by the substitution of one amino acid for another, the challenge arises of identifying one pathogenic one from the huge variety of benign variants that carries which each individual is.

G) Genetic testing: counseling and ethical considerations. Genetic testing is becoming increasingly accessible. Families and clinicians can use genetic testing to confirm diagnosis and inheritance patterns, and perhaps in the future, participate in gene-specific therapy studies. Genetic testing can have significant and far-reaching consequences for an individual and their family. A patient intending to undergo genetic testing may need to think about how he will inform his relatives, incl. further, how the results of the test will affect his decision to have children and other life-determining decisions, and about related aspects, such as health and life insurance. When referring for genetic testing, counseling and informed consent are important.

1. Prognostic or presymptomatic examination. For late-onset diseases for which the gene responsible for their development is known (for example, TIMP3 and Sorsby's fundus dystrophy), clinically healthy individuals with a 50% risk may agree to undergo genetic testing to determine whether they are carriers. For late-onset genetic diseases, such as Huntington's disease and cancer predisposition syndromes, high-quality counseling protocols are important, taking into account the pros and cons of the study, the impact of its results on the patient and his life-determining decisions, psychological support in adapting to the results and other aspects such as insurance.

The principles of management of patients who have received a diagnosis of incurable progressive vision loss that will affect their life choices, dependency on care and emotional well-being are consistent.

2. Media examination. For recessive X-linked diseases, once a patient has been identified as having a genetic mutation, other members may agree to undergo carrier testing. In case of related marriages, spouses will be able to find out if they are a pair of carriers. Women may agree to be tested for X-linked diseases to decide whether to have children, perform prenatal testing, or to be more aware and prepared for the development of the disease in future sons. The implications of this information for the couple and the support that may be required after the survey has been completed should be considered as part of the screening process.

3. Examination of children. Indications for examination may arise in cases of diseases that debut in childhood, when the results of the analysis will affect the management of the patient or the decision on assistance in upbringing/education. However, careful counseling and preparation of parents for such decisions is important, since information about genetic status and risks can greatly influence the child's parenting process. For diseases that may not become clinically apparent until adulthood, it is usually recommended to wait until the patient is old enough to make decisions for themselves.

4. Prenatal examination. If there is a known genetic mutation in the family, the spouses have the opportunity to conduct prenatal diagnosis. Chorionic villus sampling (at 11 weeks) and amniocentesis (at 16 weeks) allow accurate genetic diagnosis. Because these tests are invasive, there is a small risk of miscarriage.

It is necessary to pay attention to the reasons that motivate individuals to undergo testing. The decision to terminate or continue pregnancy if the test results are positive is made individually based on personal experience, resistance to stress (coping strategies) and available support. Although prenatal examination is rarely performed for late-onset eye diseases, in families with early onset blindness or multiple congenital anomaly syndromes, such as Lowe's and Norrie's diseases, prenatal diagnosis is advisable, and if pathology is detected, termination of pregnancy.

Preimplantation genetic diagnosis involves the examination of IVF embryos before implantation into the uterus. Such testing is becoming available for several genetic eye diseases, but poses new ethical issues that will have to be addressed in counseling.

d) Clinical examination. A clinical examination may be as important as a genetic laboratory test. Individuals who do not complain may have subtle ocular changes that indicate their genetic status. Therefore, the ophthalmologist should be prepared to inform and counsel the patient prior to testing for hereditary eye diseases so that the patient is informed and prepared in the event that genetic abnormalities are identified.

Clinical genetics. E.F. Davydenkova, I.S. Lieberman. Leningrad. "Medicine". 1976

LEADING SPECIALISTS IN THE FIELD OF GENETICS

Amelina Svetlana Sergeevna - professor of the department for the course of genetics and laboratory genetics, Doctor of Medical Sciences. Geneticist doctor of the highest qualification category

Degtereva Elena Valentinovna - assistant of the department for the course of genetics and laboratory genetics, geneticist of the first category

Page editor: Kryuchkova Oksana Aleksandrovna

The eye has long been one of the favorite objects of observation in medical genetics. Its accessible position, the possibility of dynamic monitoring of the state of its external parts, media and fundus, relatively good knowledge of the structure of the eye tissues, and the brightness of the clinical manifestations of most ophthalmological diseases make it easier to study the hereditary pathology of the eye than the pathology of any other organ.

Large studies on ophthalmogenetics have been carried out by Nettleship, Bell, Uscher, Franceschetti, Waardenburg, Francois, etc.

In our country, due to the complete elimination of some infectious eye diseases and a sharp decrease in others, the proportion of congenital and hereditary eye defects has increased significantly. Thus, according to our data, among 154 Leningrad schoolchildren who were blind from birth, 36 had a hereditary disease.

The works of S. A. Barkhash, S. N. Gorkova, O. A. Panteleeva, E. I. Starodubtseva, N. S. Eremenko and others speak about the great importance of hereditary eye pathology. However, it should be noted that our own experience of medical genetic consultations with our ophthalmologists are still small.

The material in this chapter is arranged according to the principle adopted when presented in most manuals on eye diseases. Inheritance of eye changes in diseases of other systems and organs is discussed in the relevant chapters.

REFRACTION ANOMALIES

The issue of inheritance of clinical refraction has been studied for a long time. The relationship between environmental factors and heredity in the development of eye refraction still causes controversy. Studying refraction in 50 pairs of twins, we were convinced that the coincidence of refraction in monozygotic twins was in 30 pairs out of 32, and among bizygotic twins - in only 4 pairs out of 18 (G. M. Chutko et al., 1971).

The complexity of the issues of inheritance of refraction is clearly visible when considering views on myopia - a refractive error, which is one of the most common causes of decreased vision and, from the genetic point of view, the most studied type of refraction.

Already at the beginning of the 19th century. ophthalmologists observed that myopia often occurred in many members of the same family, and argued in favor of a hereditary origin of myopia.

The concept of predisposition to myopia was introduced. This is a predisposition that a person has even before he is born. Under the influence of environmental factors, it leads to refractive error. The predisposition is inherited.

In 1913, Steiger wrote that myopia is a hereditary condition. Steiger pointed out that refraction depends on the length of the axis of the eye and on its refractive power. But he believed that the relationships between these factors were purely random. As always happens when, ignoring the integrity and complexity of a problem, they focus on absolutely only one aspect of it, his followers lost sight of the other side - the influence of the external environment.

Determining the type of inheritance of myopia is difficult due to the different manifestations of hereditary predisposition. An important question is whether one or more genes are involved in the development of predisposition to myopia, that is, whether monogenic or polygenic inheritance occurs. We should probably think about the polygenic cause of myopia.

D.I. Berezinskaya (1925) believed that myopia is inherited as a monogenic recessive; she provides the results of an examination of children born in marriage between myopes and persons with a different refraction, and children born from marriage between myopes. She finds that the study results provide evidence for recessive inheritance of myopia.

A. A. Kholina (192e) considered myopia to be a recessively inherited trait, “depending on at least two, to a certain extent, independently mendelian inclinations (genes).” According to this opinion, there are at least 2 genetically distinct forms of myopia.

Wold (1949) notes that there can be both a paratypic form of myopia and inherited myopia (inherited both recessively and dominantly).

P. A. Andogsky (1930) considered the cause of hereditary myopia to be the transfer of “thinness and pliability of the eye wall”, the hereditary conditioning of the deep orbits.

E. J. Tron (1947) wrote that myopia is heterogeneous in its origin; he divided myopia into school and progressive, considering the first to be a biological variant closely related to inheritance. E. Zh. Tron noted that optical elements are subject to mutual influence during the development of the body, which contributes to the approach of refraction in most people to emmetropia.

E. S. Avetisov (1967) writes that “the role of heredity in different forms of myopia and in different individuals is not the same.”

According to A. A. Malinovsky (1970), myopia, in contrast to a number of monogenically transmitted lesions of the organ of vision

is polygenically determined, and a hereditary predisposition to myopia manifests itself with varying expressiveness under the influence of environmental factors. Therefore, it seems important to early identify the most endangered populations and apply broad preventive measures.

Farsightedness (hypermetropia) is usually congenital. In terms of genetics, it has been studied less than myopia. When citing pedigrees of individuals with high hypermetropia, many researchers consider the autosomal recessive type of inheritance to be the most common.

Waardenburg (1961, 1963) believed that dominant transmission of this refractive error was also possible.

High hypermetropia is often one of the symptoms of microphthalmia, flat and small cornea, aphakia and other diseases accompanied by a violation of the proportionality of the refractive power of the optical system and the length of the axis of the eye.

Everything that has been said about farsightedness and myopia also applies to astigmatism. It should be emphasized that we often see not only the same degree of astigmatism in different generations, but also the coincidence of the main axes of astigmatism in parents and descendants.

STRABISMUS

Concomitant strabismus is the result of a disorder of binocular vision mainly due to refractive errors.

The significant role of heredity in strabismus is noted by many authors. E. M. Fisher (1958) wrote that there are many cases when the parents or close relatives of a squinting child are found to have strabismus. Pratt-Johnson and Lunn (1967) found 65% of hereditary causes of concomitant strabismus. However, E.M. Fisher emphasizes that strabismus is caused by the inheritance of refractive errors, as well as a weakened desire for binocular vision.

N.I. Pilman (1964) criticized the position expressed by some experts: if one of the family members once had strabismus, which subsequently disappeared spontaneously, then in subsequent generations it will disappear on its own. N.I. Pilman believes that such a “self-healed” person does not have binocular vision, and that the doctor should not wait for self-healing, but actively treat the mowing child.

In our practice, we sometimes encountered dominantly inherited accommodative strabismus. However, our experience does not yet allow us to conclude that different family members have the same prognosis. Each patient has to be prescribed treatment according to an individual plan.

Most experts consider the main type of inheritance of strabismus to be dominant. The recessive type of inheritance is much less common. It is probably correct to consider the inheritance of strabismus to be polygenic.

CONGENITAL DISORDERS OF COLOR SENSATION

Congenital color blindness is a common deficiency of eye function. According to domestic sources, the frequency of congenital color vision disorders among men averages 8%, and among women - 0.5%.

Among the various forms of color vision disorders, the most common is red or green color blindness (protanopia and deuteranopia). This color blindness is inherited from the grandfather to the grandson born from the daughter. This pattern of inheritance of the disease was called the Iiorner-Nasse law (but after Horner, who formulated it for color vision impairment, and Nasse, who formulated it for hemophilia).

Genes influencing the appearance of color vision disorders and other gender-related diseases are localized on the X chromosome; the gene for normal color vision is dominant in relation to the recessive gene for impaired color vision (Table 19).

It is believed that every sixth woman is a conductor - a carrier of the color blindness gene. Interestingly, among women suffering from Shereshevsky-Turner disease (they have only one X chromosome), color blindness is much more common than usual. This is well illustrated by the pedigree described by Lenz (1957). In this pedigree, two brothers are color blind, their sister is probably a conductor. From the marriage of this woman with a flower-blind man, a flower-blind son and daughter were born. The fact that the son is color blind is easily explained. The daughter should not have had this anomaly if she had two X chromosomes. But the daughter had Shereshevsky-Turner disease, that is, she had only one X chromosome (the carrier of the color blindness gene), treated from her mother, and therefore color blindness manifested itself.

There is no data yet regarding the inheritance of a rare form of congenital violet color blindness (tritanopia).

Some authors believe that complete color blindness (monochromasy) can be inherited, but the type of inheritance has not been established. Other authors question the fact of inheritance of color blindness in all three colors.

A rare congenital disease “achromatopia” is characterized by a lack of color perception for all colors (monochromasia), amblyopia, nystagmus, photophobia, nyctlopia, central scotoma, and astigmatism. Often the disease is combined with atro

optic nerve disease, retinitis pigmentosa, retinitis albescens or macular degeneration.

TABLE 19 Hereditary transmission of color vision disorders

E. E. Somov in 1963 described this disease in a brother and sister.

CHANGES IN THE EYELIDS AND TEAR DUCT

Ankyloblepharon. Ankyloblepharon is a congenital pathology in which the edges of the eyelids are fused together for some distance, as a result of which the palpebral fissure is shortened. This pathology can also be in the form of bridges dividing the palpebral fissure in half.

The etiology of this disease is unknown. Heredity plays a significant role. The disease is inherited in a dominant manner. Fine (1933) reported his observation in which a mother and two sons were affected; Fiolho (1929) described ankyloblepharon in a man, 3 of his 9 sons and 1 granddaughter; descriptions of family cases are also given by Ashley (1947) and others.

Epicanthus. The epicanthus is a semilunar fold of skin covering the inner commissure of the eyelids. Epicanthus is often found among representatives of the Mongolian race. It is believed that all children have it in utero, but in most newborns of the European race, the epicanthus disappears at the time of birth or later as the dorsum of the nose grows. Epicanthus can be inherited according to the dominant type. Numerous studies point to precisely this transmission of this trait.

Epicanthus is a common symptom in embryopathies and many hereditary diseases of the body (for example, chromosomal diseases).

Congenital ptosis. There are simple congenital ptosis associated with levator palsy, and ptosis combined with other congenital somatic defects and defects of the nervous system.

The inheritance of ptosis is well known. Numerous works are devoted to this issue. One of them describes a family in which out of 128 people in 6 generations, 64 people had ptosis. In this family, ptosis was transmitted dominantly.

Probably, each ophthalmologist has his own observations of families in which this anomaly is inherited. In one of the families we examined, bilateral congenital ptosis was passed on in four generations according to the dominant type.

L.A. Dymshits (1970) noted that isolated ptosis is transmitted only dominantly, and in combination with epicanthus - both dominantly and recessively.

Congenital blepharophimosis. The concept of “congenital blepharophimosis” usually includes three anomalies: ptosis, epicanthus, shortening of the palpebral fissure. This pathology is always bilateral and is congenital. Such patients have a peculiar appearance. They are very similar to each other, their heads are usually thrown back upward, and due to the narrowness and shortening of the palpebral fissure, it seems that they are constantly squinting. The disease is difficult to treat surgically. Sometimes other pathological changes are found in such patients (microphthalmos, microblepharon).

The disease is often sporadic, but can be inherited. Most authors believe that the form of inheritance of the disease is dominant. Dimitri (1922), the first to propose naming this disease, cites a pedigree in which in 5 generations 21 out of 38 people suffered from blepharophimosis.

A. A. Akhmedzyanov and V. I. Nasyrova in 1965 published observations of a family in which congenital ptosis, epicanthus and shortening of the palpebral fissures have been transmitted for 143 years. Of the 105 family members, 27 people inherited this anomaly. According to the authors' observations, females who had an anomaly often suffered from menstrual irregularities and infertility. Assessing the given pedigree, one should classify this pathology as a disease with a dominant type of inheritance.

We observed an 8-year-old girl who suffered from blepharophimosis; a father and his son from another marriage suffered from the same disease; dominant transmission of the disease was also observed in two other families.

Blepharochalasis. This term refers to the drooping of the skin folds of the upper eyelid. Usually this disease is acquired, but congenital blepharochalasis also occurs. Congenital blepharochalasis is often hereditary and inherited in a dominant manner. Paimeton (1936) described a family in which 13 males and 38 females had this anomaly in 3 generations. Badtke (1961) also notes it in 3 generations.

Distichiasis. Distichiasis - double growth of eyelashes. With this congenital disease, eyelashes grow along both the anterior and posterior edges of the eyelids. This anomaly is often bilateral.

A large number of cases of inheritance of distichiasis have been described. Waardenburg (1963) believes that distichiasis is inherited in a dominant manner.

Congenital entropion of the eyelids. This pathology is not common, but there are already a sufficient number of descriptions of the dominant inheritance of such a disease.

Xanthelasmas. Xanthelasmas are inherited in a dominant manner. Currently, xanthelasma is considered a cutaneous manifestation of hypercholesterolemic and hyperlipemic xanthomatosis.

Dacryocystitis. In addition to numerous cases of dacryocystitis, which are caused by environmental factors and are well known to all ophthalmologists, there are also those in which dacryocystitis is hereditary.

Many authors write about congenital dacryocystitis, observed in several family members and transmitted dominantly.

It is believed that congenital dacryocystitis is hereditary in 9% of cases.

B. L. Polyak and F. A. Popova (1929) described hereditary dacryocystitis in two families. It is interesting to note that in one of the families, the disease began at the age of 25 in all three individuals. The authors believe that in these families there was a pathology of the nose (its flattening, reduction in the size of the shells), which was inherited and led to secondary inflammatory changes in the lacrimal sac.

Using the example of hereditary dacryocystitis in adults, it is clear that a well-collected anamnesis can reveal the influence of heredity even in those diseases in which the possibility of inheritance is little known.

Dacryocystitis of newborns is far from a rare phenomenon. The literature has raised the question of whether the delay in the reverse development of the connective tissue membrane that closes the lacrimal ducts is, in some cases, hereditary. According to many pedigrees, dacryocystitis of newborns can be inherited in a dominant manner.

APLASIA AND DYSPLASIA OF THE EYEBALL

Microphthalmos. Microphthalmos (reduction in the size of the eyeball) is a common congenital anomaly. Microphthalmos can be expressed to varying degrees. Sometimes the size of the eyeball is reduced so much that they even speak of incomplete anophthalmos. With microphthalmia, there is always a decrease in the size of the palpebral fissure and cornea. Microphthalmia without pathology of the lens and choroid is inherited in a recessive manner.

Parents of sick children are usually healthy. In many described cases of such microphthalmia, consanguineous marriages are noted among the parents of patients.

V.P. Efroimson (1968) points to the possibility of inheriting microphthalmos as an X-linked recessive.

If microphthalmos is associated with coloboma of the eyeball, i.e., with non-closure of the optic cup in the embryonic period of development, then the disease is inherited dominantly. In such cases, this pathology is usually combined with clouding of the cornea, cataracts, and other anomalies of the eye and the whole body.

Anophthalmos. Anophthalmos is the absence of an eye. Congenital anophthalmos is called complete when, even with careful examination, no traces of the eyeball can be detected in the orbit. Usually, both the optic nerve and the chiasm are absent. Often it is not possible to detect even the optical opening of the orbit.

In cases where the disease is not a phenocopy, it is inherited in a recessive manner. In all cases described in the literature, inherited anophthalmos was bilateral, and the consanguinity of the parents was noted.

It is necessary to very carefully compare aplasia and dysplasia of the eye with other malformations of the body, since there is a certain connection between various combinations of anomalies and the types of inheritance of anophthalmos and microphthalmos.

In addition to genetic inheritance, microphthalmos and anophthalmos can be the result of chromosomal aberration (for example, in Patau syndrome).

Cryptophthalmus. Cryptophthalmos or ablepharia is a congenital malformation in which the palpebral fissure is absent, the skin of the forehead passes into the skin of the cheek without a break in the orbital area. Structural elements of the eyelids are often missing. The eyeball with this anomaly is underdeveloped (microphthalmos or anophthalmos).

Cryptophthalmos can be combined with other developmental defects: clefts of the face, palate, lips, syndactyly, etc.

The disease is rare. L.A. Dymshits and E.M. Yufit (1960) note that only 30-40 cases of cryptophthalmos have been described.

L.A. Dymshits and E.M. Yufit give a pedigree in which a 3-year-old girl had bilateral cryptophthalmos, her older brother had left-sided cryptophthalmos (the other brother is healthy); Both brothers of the girl's father also had cryptophthalmos (the eldest had unilateral, the younger had bilateral). The girl's parents did not have any pathological changes in their eyes. From this small pedigree it is clear that in two generations a significant number of family members had cryptophthalmos. In our opinion, in the pedigree given by L.A. Dymshits and E.M. Yufit, cryptophthalmos was inherited dominantly with incomplete manifestation. Most other authors note that the disease is inherited recessively.

We saw one infant with bilateral cryptophthalmos, but we were unable to obtain any information about the presence of this defect in other family members; It was also not possible to connect the appearance of this defect with any disease of the mother during pregnancy. Thus, in our case, we can think about either the sporadic occurrence of the defect or its recessive inheritance.

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