Symptoms and treatment of connective tissue dysplasia. Connective tissue dysplasia: main clinical manifestations, complex therapy, prevention

Connective tissue dysplasia, or DST, is a genetically determined (due to genetics) condition of 35% of the entire population of the Earth - such data are provided by Professor Alexander Vasiliev, head of the laboratory of the Hematological Research Center under the Ministry of Health of the Russian Federation. Officially, CTD is usually called a systemic connective tissue disease, although the term "condition", due to the prevalence of the phenomenon, is used by many scientists and doctors. Some foreign sources call the proportion of dysplastics (who suffer from dysplasia to varying degrees) - 50% of all people. This discrepancy - from 35% to 50% - is associated with different international and national approaches to classifying a person as a disease group.

Connective tissue dysplasia

The presence of many approaches to the definition of the disease indicates an incomplete study of the issue. They began to take it seriously quite recently, when interdisciplinary medical institutes appeared and an integrated approach to diagnostics began to develop. But even now, in a conventional hospital, connective tissue dysplasia is not always diagnosed due to its multidimensionality and the complexity of the clinical picture.

Connective tissue dysplasia: pathology, its types and clinical manifestations

CTD is characterized by genetic disorders in the development of connective tissue - mutational defects in collagen and elastin fibers and the ground substance. As a result of fiber mutations, their chains are formed either short relative to the norm (deletion) or long (insertion), or they are affected by a point mutation as a result of the inclusion of the wrong amino acid, etc. The quantity / quality and interaction of mutations affect the degree of manifestation of CTD, which usually increases from ancestors to descendants.

Such a complex "technology" of the disease makes each CTD patient unique, but there are also stable mutations that lead to rare types of dysplasia. Because allocate two types of DST - differentiated and undifferentiated.

Differentiated connective tissue dysplasia, or DDST , is characterized by a certain type of inheritance of traits, a clear clinical picture. It includes Alport syndrome, Marfan, Sjogren, Ehlers-Danlos syndromes, joint hypermobility, epidermolysis bullosa, "crystal man disease" - osteogenesis imperfecta - and others. DDST is rare and is diagnosed fairly quickly.

Undifferentiated connective tissue dysplasia, or UCTD , manifests itself very diversely, the lesions are multi-organ in nature: several organs and systems are affected. The clinical picture of UCTD may include individual small and large groups of signs from the list:

• Skeleton: asthenic build; disproportionate elongation of limbs, fingers; a variety of vertebral deformities and funnel-shaped / keeled deformities of the chest, different types of flat feet, clubfoot, hollow foot; X / O-shaped limbs.
• Joints: hypermobility, hip dysplasia, increased risk of dislocations and subluxations.
• Muscular system: lack of mass, especially oculomotor, cardiac.
• Skin: the integuments are thinned, hyperelastic, have increased trauma with the formation of scars with a “tissue paper” pattern and keloid scars.
• Cardiovascular system: altered anatomy of the heart valves; thoracodiaphragmatic syndrome caused by vertebral pathologies and pathologies of the chest (thoracodiaphragmatic heart); damage to arteries and veins, including - varicose lesions at a young age; arrhythmic syndrome, etc.
• Bronchi and lungs: bronchiectasis, spontaneous pneumothorax, ventilation disorders, tracheobronchial dyskinesia, tracheobronchomalacia, etc.
• Gastrointestinal tract: violation (compression) of the blood flow supplying the abdominal organs with blood - dysplasia is unsuccessfully, for a long time, sometimes for a lifetime, treated by a gastroenterologist, while the cause of the symptoms is connective tissue dysplasia.
• Vision: myopia of varying degrees, elongation of the eyeball, dislocation of the lens, blue sclera syndrome, strabismus, astigmatism, flat cornea, retinal detachment.
• Kidneys: renovascular changes, nephroptosis.
• Teeth: caries in early childhood, generalized periodontal disease.
• Face: malocclusion, pronounced facial asymmetries, gothic palate, hair growing low on the forehead and neck, large ears or “crumpled” auricles, etc.
• Immune system: allergic, autoimmune syndromes, immunodeficiency syndrome.
• Mental sphere: increased anxiety, depression, hypochondria, neurotic disorders.

This is far from a complete list of consequences, but characteristic: this is how connective tissue dysplasia manifests itself in children and adults. The list gives an idea of ​​the complexity of the problem and the need for a rigorous study to make a correct diagnosis.

hip dysplasia

hip dysplasia- deviation, disturbance or pathology in the development of articular structures in the pre- and postnatal periods, the result of which is an incorrect spatial-dimensional configuration of the joint (correlation and juxtaposition of the acetabulum and the femoral head). The causes of the disease are varied, including may be due to genetic factors, such as connective tissue dysplasia.

In medicine, it is customary to distinguish three forms of development of DTS - pre-dislocation (or the stage of an immature joint), subluxation (the stage of initial morphological changes in the joint) and dislocation (pronounced morphological changes in the structure).

The joint at the pre-dislocation stage has a stretched, weak capsule, and the femoral head freely dislocates and returns to its place (slip syndrome). Such a joint is considered immature - formed correctly, but not fixed. The prognosis for children with this diagnosis is the most positive if the defect is noticed in time, and the therapeutic intervention began on time and was carried out effectively.

The joint with subluxation has a displaced femoral head: its displacement in relation to the acetabulum can occur to the side or upward. At the same time, the general arrangement of the cavity and the head is preserved, the latter does not violate the limits of the limbus - the cartilaginous plate of the cavity. Competent and timely therapy implies a high probability of the formation of a healthy, full-fledged joint.

The joint in the dislocation stage is, in all respects, a displaced femoral head, the contact between it and the cavity is completely lost. This pathology can be both congenital and the result of incorrect / ineffective treatment of earlier stages of dysplasia.

External signs for making a preliminary diagnosis of DTS in infants:

• quantitative limitation in hip abduction;
• shortened thigh - with the same position of the legs, bent at the knees and hip joints, the knee on the affected side is located lower;
• asymmetry of the gluteal, under the knees and inguinal folds on the legs of the child;
• Marx-Ortolani symptom (also called the click or slip symptom).

If an external examination gives positive results for diagnosing DTS, then an accurate diagnosis is made according to the results of ultrasound and X-ray examination (after 3 months).

Confirmed hip dysplasia is treated, depending on the general form and secondary features, with the help of Pavlik stirrups, plaster garters, other functional devices and physiotherapy, in case of severe pathologies - with surgical methods.

Connective tissue dysplasia in children

Connective tissue dysplasia in children can "declare" itself at any age of the child. Often, the clinical signs become more distinct with growing up (“the effect of the manifestation of the negative of the photograph”), and therefore the exact definition of the disease in childhood and adolescence is difficult: such children are simply more likely than others to come to one specialist with problems, then to another.

If the child is diagnosed with connective tissue dysplasia, and it is authoritatively confirmed, then do not despair - there are many methods of supportive, corrective and restorative therapy. In 2009, for the first time in Russia, a basic drug program was defined for the rehabilitation of patients with CTD.

In addition, dysplastics have their own proven advantages over relatively healthy people. As Professor Alexander Vasiliev says, most dysplastics have a higher (relative to average) level of intelligence - many successful people had CTD. Very often, patients with dysplasia look more attractive than the "main population", due to the elongated limbs and the general sophistication of the species. They are in 90% of cases outwardly younger than their biological age. There is another important advantage of dysplastics, confirmed by domestic and foreign observations: patients with CTD are on average 2 times less likely to experience oncological lesions.

When should parents be vigilant and start a comprehensive examination of the child in reputable clinics? If from the above list of pathologies and conditions you notice at least 3-5 in a child, you should contact a specialist. There is no need to draw conclusions on your own: even the presence of several matches does not mean a diagnosis of CTD at all. Doctors must establish that all of them are the result of one cause and are interconnected by pathology of the connective tissue.

The fibrous structures of the body may have defects. They are associated with changes in the collagen fibers of a genetic nature and relate to a problem that is referred to as connective tissue dysplasia.

Pathology extends its influence to many systems and organs where connective tissue is present, disrupting their health. A large proportion of problems of this nature in the total number of diseases occurs in the tissues of the heart. About what it is, heart dysplasia in adults and children, we will tell in this article.

Features of the disease in adults and children

The disease can designate itself immediately after the birth of a person or manifest itself gradually throughout life. In children, newborns, dysplasia of the connective tissues of the heart is most often present as a factor causing rhythm disturbances. This is: or . There may be other violations.

ICD 10 disease code: M30-M36.

In adulthood, identifying the cause of disorders, if it is connective tissue dysplasia, is as relevant as in the early years. The diagnosis becomes clear with difficulty.

Classification

An unambiguous generally accepted classification of the disease does not yet exist. One option to divide disorders into varieties is to classify them according to syndromes. Connective tissue dysplasia, which affects the tissues of the heart and causes heart disease, includes:

• Valvular Syndrome:
  • valve degeneration,
  • all kinds of prolapses caused by violations of the connective tissue.
• Vascular syndrome - a lack of components in the walls of blood vessels, painful changes in the arteries that have an elastic type:
  • vascular tone changes and differs from the norm,
  • arterial pressure tends to decrease.
• Thoracodiaphragmatic heart - the chambers have a normal structure, but their size is reduced (often the deformity of the chest provokes the disease).
• Arrhythmic syndrome occurs in more than half of patients with connective tissue dysplasia. The reason is a metabolic disorder in the muscles of the heart. may be initiated by valvular syndrome. Possible problems:
  • intraventricular and atrioventricular blockade,
  • ventricular extrasystole,
  • disturbances in the work of pacemakers,
  • syndrome of overexcitation in the work of the ventricles.
• Sudden death syndrome - this phenomenon can be caused by the action of one or more of the syndromes listed above.

Connective tissue dysplasia syndrome was defined in 1990 as a group of diseases that cause heart disease due to organic disorders in the connective tissues. The syndrome includes variants of inferior development of connective tissue, which are united by a common name - dysplastic heart.

Causes

Violations of the structure of the connective tissue can be of a different nature:

• Congenital: mutation of genes that are responsible for the creation of enzymes necessary for the synthesis of collagen and those that are directly responsible for the formation and spatial organization of collagen fibers.
• Purchased:
  • malnutrition,
  • unfavorable ecological situation.

Symptoms of connective tissue dysplasia of the heart

Signs of abnormal phenomena in the work of the heart associated with connective tissue dysplasia can be varied, because there are many options for the manifestation of the disease in the body. Vegetative disturbances and general malaise are more often observed.

• sleep disturbance,
• fatigue,
• pain in the heart,
• poor health,
• cephalgia,
• frequent pre-fainting states.

The causes of heart disease are also symptoms of possible connective tissue dysplasia:

• Features of the structure of blood vessels, the heart and its structural parts:
  • hypoplasia of the aorta or pulmonary trunk,
  • violation of the functioning of the mitral valve - prolapse of its valves,
  • problems associated with chords: excessive mobility, elongation;
  • aneurysms located in the coronary arteries,
  • functional disorders of the conduction system,
  • tricuspid and mitral valves have excess tissue on the cusps,
  • the pulmonary trunk or aorta is dilated in the proximal part,
  • valve components have degenerative changes,
  • violations in the structure of fastening chords,
  • valves have an unnatural number of leaflets,
  • myocardial bridges,
  • anomalies of the septum between the ventricles.
• Constitutional features:
  • rotation of the heart around the longitudinal and sagittal axis,
  • "drip" heart,
  • hanging heart.
• Deformities of the spine and chest, provoking heart disease.

About the data of ultrasound of the heart with dysplasia of the interatrial septum, mitral valve, left ventricle and other methods for diagnosing the disease, read below.

Diagnostics

Early identification of the problem is very important, because it makes it possible to maintain the patient's condition and prevent the progression of the disease and the consequences associated with it.

Methods applied:

• electrocardiography,
• Doppler echocardiography,
• electrocardiography of daily monitoring.

Treatment

Therapeutic measures for connective tissue diseases are based, for the most part, on general strengthening actions of a non-drug nature. The purpose of their implementation is to improve blood circulation and nutrition of tissues with the missing components for their full functioning. It is also important to choose a daily routine for the patient that provides for useful loads and timely rest.

Therapeutic

Therapeutic treatment of cardiac dysplasia:

• physiotherapy exercises - loads are selected taking into account the individual characteristics of the patient;
• psychotherapy,
• physiotherapy,
• autotraining,
• water treatment,
• spinal massage,
• yoga exercise,
• acupuncture.

Medical

Taking drugs aimed at the following result:

• enrichment of the body with magnesium,
• metabolic nature, nourishing tissues with essential amino acids,
• agents that increase collagen formation;
• reduction of manifestations of vegetative-vascular dystonia,
• bringing the nervous system to a calm state,
• prevention of myocardial neurodystrophy,
• prophylaxis with antibiotics.

Drugs are used if there is a doctor's prescription:

• magnerot,
• coenzyme,
• panangin,
• vitamins,
• carnitine,
• preparations containing fatty acids.

Folk methods

Treatment with infusions and decoctions of herbs is allowed, you should first coordinate the appointment with the doctor.

Apply:

• hawthorn,
• sage,
• motherwort,
• valerian,
• wild rosemary.

Prevention

If there are people in the family who have a problem with connective tissue disorders, then it is important:

• that all family members are supervised by one specialist,
• the family doctor undertakes to coordinate the observation of family members by other specialists,
• in such families, measures for advance family planning are designated as prevention.

Complications

Patients with a problem of connective tissue disorders should be in the field of observation of specialists. If the condition of the tissues is not maintained in a timely manner, and the diseases caused by this phenomenon are not treated, then further progression of the pathology and serious consequences are possible.

Connective tissue without special therapy can undergo degradation, degeneration and necessitate surgical intervention, if possible, such as valve replacement. If the operation is not possible, then irreversible phenomena can lead to death.

Forecast

Let's talk about the prognosis for connective tissue dysplasia syndrome with heart disease. If the patient follows the recommendations of a specialist, treats his health with attention, periodically undergoes preventive courses of treatment, then a positive prognosis with a normal quality of life is possible.

Even more useful information about the features connective tissue dysplasia of the heart:

“Dis” is a prefix to a word that denies its positive meaning, “plasis” is development or formation. Accordingly, dysplasia is a phenomenon that describes a violation of the formation or development in this case of connective tissue. This tissue is ubiquitous and accounts for half of the human body weight. Most often, it is not directly responsible for the work of organs, but performs an auxiliary function. But since its mass is about 60%, and sometimes 90% of the mass of the organ, violations of its formation can seriously affect the work of the organ whose connective tissue has suffered.

Connective tissue dysplasia or DST is a whole complex of systemic diseases of a non-inflammatory nature. They are based on changes in collagen, fibroblasts, elastic fibrils, glycoproteins (biopolymers) and complex proteins called proteoglycans.

Sometimes other names are used to define this disease: connective tissue insufficiency, congenital collagenopathy. And if we are talking about joints, then the disease can be called hypermobility syndrome.

Connective tissue begins to form from the first days of the life of the embryo. Serious anomalies in its formation may be incompatible with life.

Connective tissue

Most often, the concept of "connective tissue" (CT) in humans is associated with cartilage, ligaments or fascia. These formations really belong to her. But in fact, there are several types of connective tissue. The connection between them is defined:

1. Origin (from the mesodermal parenchyma).
2. structural similarity.
3. Functionality (performing supporting functions).

Connective tissue forms a supporting frame (stroma) for any organ and its outer cover. For any ST, it is customary to distinguish three main functions:

• Protective.
• Trophic (nutrition).
• reference.

Modern anatomy in the category of ST includes:

• Cartilage and ligaments, articular bags and tendons, bones, perimysium and muscle sheath, sarcolemma (muscle cell membrane/fiber).
• Sclera, iris.
• Microglia, blood, synovial and intercellular fluid, lymph and others.

It can be both normal and have deviations:

1. In the direction of increased elasticity.
2. In the direction of increased stretch.

In the first case, medical practice did not record any deviations in the functioning of the body as a whole or individual organs. In the second case, deviations are observed and there are many such deviations. Therefore, medical scientists have singled out a complex of these deviations in a separate syndrome with the abbreviation SDST.

The most common visible manifestations of this syndrome are skeletal, muscle, and skin changes.

Although connective tissue dysplasia is not limited to these manifestations. And given such a variety of connective tissue structures, the polymorphism (diversity) of symptoms that demonstrates a defect in the development of these tissues becomes understandable.

Information about dysplasia

What is meant by connective tissue dysplasia? This is a group of diseases that is genetically determined and has heterogeneous symptoms, as well as. Violation of the formation of connective tissue occurs during periods of intrauterine or postnatal development. The disease is multi-symptomatic, because it can affect not only the joints and ligaments, but also manifest itself in the form of a malfunction of the internal organs.

Today, 14 types of fibrillar protein (collagen) are known, which is the basis for the construction of connective tissue. The process of its formation is not simple, and therefore, with gene mutations, it can be disrupted at any stage. As a result, “wrong” collagen is formed.

With serious mutations, changes in organs are so strong that they may even be incompatible with life or cause serious pathology. But more often one or more pathological signs are inherited, for example,.

It is officially believed that this connective tissue dysplasia occurs in less than 10% of the world's population.

But presumably, individual symptoms or minor forms of the disease, upon careful examination, can be detected in more than 60% of people considered healthy in terms of the development of TS.

The reasons

The main cause of the disease is a persistent change in the genes (mutation) responsible for the production of fibrillar protein, the necessary enzyme, carbohydrate-protein complexes or coenzymes. The synthesis of this protein is encoded by several dozen genes (about 40). Just over 1,000 possible mutations have been described to date. The process of discovering new genetic breakdowns is incomplete.

Mutagenic factors that lead to dysplastic phenomena include:

• Complications during childbearing.
• Psycho-emotional stress.
• Pernicious habits of the mother (smoking, alcoholism, drug addiction).
• Ecology and industrial hazards.
• Diet errors (eating fast food, malnutrition, lack of nutrients, in particular magnesium).

Mutations lead to three types of protein chain abnormalities:

• Elongation, or insertion.
• Shortening, that is, to a deletion.
• Point mutation (substitution of one of the amino acids).

Any of these disorders affects the ability of the connective tissue to withstand mechanical stress and is the cause of a change in the quality characteristics of the tissue.

When mutations first appear, they are usually subtle. The disease is not diagnosed, external manifestations are usually mistaken for phenotypic (external) features.

But from generation to generation, mutations accumulate, especially when two dysplastics meet, and characteristic clinical signs appear that are not limited to external defects. Pathology can affect the articular-ligamentous apparatus and internal organs.

Classification

How connective tissue dysplasia should be classified is one of the most controversial issues in medicine. There is no single classification. Attempts to classify it come down to several ways to distinguish types of pathology on the basis of:

1. Differentiation.
2. Generalizations (generalized, non-generalized).
3. The presence or absence of syndromes (syndromic, non-syndromic).
4. According to the severity of the symptoms.

Generalized include types of dysplastic changes that combine the involvement of at least three organs or systems in the pathological process. If CTD is manifested by phenotypic changes and affects at least one organ, such dysplasia is usually referred to as syndromic. According to the severity, it is customary to distinguish three forms:

1. Isolated forms.
2. Small forms.
3. Actually hereditary DST.

In the first case, pathological changes affect only one organ. In the second, three signs are diagnosed.

If possible, it is customary to differentiate the disease according to phenotypic (external) signs:

1. Differentiated dysplasia (DDST).
2. Undifferentiated dysplasia (NDST).

Consider differentiated and undifferentiated dysplasia in more detail.

Differentiated

This type of dysplasia is rare. An attempt to classify it was made in 2000 by a professor at the Department of Genetics of the University. Mechnikov, geneticist and pediatrician Kadurina. It is her classification that is now used, although it is limited only to hereditary syndromes.

Differentiated dysplasia includes specifically described disorders caused by known mutations in certain genes. At the same time, the type of biochemical disorders is clearly defined.

The most typical hereditary disorders in DDST are:

• Beals syndrome or hereditary deformity of the fingers (arachnodactyly).
• Syndrome "crystal man" (impaired osteogenesis, leading to brittle bones).
• Ehlers-Danlos syndrome (too elastic and vulnerable skin). As part of this syndrome, the patient may show hypermobility of the joints, ophthalmic pathologies, prolapse of internal organs (ptosis), and bleeding.
• Skin atrophy (elastosis).
• Disorders of the metabolism of glycosaminoglycans (mucopolysaccharides).
• Marfan syndrome (includes skeletal, myocardial and ophthalmic pathologies).
• Scoliosis is dysplastic.

undifferentiated

Undifferentiated connective tissue dysplasia is characterized by signs that cannot be placed in the structure of hereditary syndromes described above. The frequency of this pathology is high. It is believed that its detection among the population reaches 80%.

Non-syndromic dysplasia is usually divided into several phenotypes. The main ones are 3:

1. Ehlers-like (excessive skin elasticity, increased joint mobility, generalized dysplasia).
2. MASS-like (thinning of the skin, anomalies in the structure of the skeleton, increased joint mobility, generalized dysplasia).
3. Marfanoid (damage to the valves of the myocardium, ophthalmopathology, arachnodactyly, generalized dysplasia in combination with increased leanness).

Main features

Connective tissue dysplasia is characterized by such a variety of clinical manifestations that it is difficult to briefly describe them or select the leading symptoms. Therefore, medical science has identified a number of common signs, which include weakness, indigestion, headaches and breathing problems. External signs that are easy enough to diagnose, and symptoms that describe violations of the main systems:

• Cardiac and bronchopulmonary disorders.
• Ophthalmic pathologies.
• Anomalies in the structure and functioning of the skeleton and joints.
• Changes in the urinary system.
• Diseases of the gastrointestinal tract.
• reproductive disorders.
• immunological changes.
• Blood pathologies.
• Neurogenic and mental illnesses.

When examining patients with a diagnosis of CTD, one can see:

1. Features of their constitution: asthenic constitution of the body, growth is usually above average, narrowness in the shoulders.
2. Microanomalies: protruding ears, low hairline, etc.
3. Anomalies in the development of the skeleton, if any.
4. Altered epidermal layer (its thinness, hemangiomas, spider veins or teleectasias and excessive elasticity), etc.

A striking example of skeletal anomalies can serve as deformities of the sternum and chest as a whole ("chicken breast" or keel deformity and changes in the form of a funnel),. Often the leg or both suffers in the form of O or X-deformity, lengthening, changes in the foot (flat feet, lengthening), etc.

The following symptoms are recognized as characteristic for connective tissue deficiency: "cleft lip" and "cleft palate", impaired growth of teeth and bite. CT weakness leads to weakness of the muscle system that supports the internal organs, and their descent to the torticollis.

Dysplasia of the heart

Cardiac disorders or the syndrome of connective tissue dysplasia of the heart is a whole group of syndromic conditions. These include:

• Arrhythmias.
• Vascular pathologies.
• Thoracodiaphragmatic syndrome (myocardial chambers are reduced due to dysplastic changes in the chest).
• Violation of the work and structure of the valvular apparatus (all kinds of prolapses).
• Defect of the IPP (interatrial septum).

DSTS is often manifested by excessive mobility of myocardial chords, the appearance of an additional chord, an open foramen ovale, thinning of the walls of the largest unpaired vessel (aorta), and hypertension.

A feature of the syndrome of connective tissue dysplasia of the heart is that the pathology, proceeding with significant changes in the CT of the heart, often causes sudden death of the patient.

Heart dysplasia is often combined with pathological changes in the respiratory system (bronchiectasis, emphysema, spontaneous pneumothorax, etc.). It is accompanied by migraine, lability of the nervous system, speech disorders and enuresis.

Ophthalmic pathologies most characteristic of CTD are:

• Violation of vision.
• Subluxation of the lens.
• Astigmatism.
• Strabismus.

Diseases of the digestive system are most often expressed in diverticula, hernias and weakness of the gastric sphincters.

In women, dysplastic changes can cause uterine prolapse, self-abortions, and a rare pathology of the placenta - MDP (mesenchymal dysplasia). Men may have cryptochirism. This change in internal organs is not limited. Sometimes there is a doubling of the kidneys, a change in their shape. Patients with CTD often suffer from respiratory problems and allergies.

Diagnostics

Diagnosis of this pathology is not always carried out correctly and in a timely manner due to the large number of various symptoms. The diagnosis of undifferentiated connective tissue dysplasia is particularly difficult, mainly due to the lack of uniform diagnostic criteria.

Combinations of external (phenotypic) signs and pathology of internal organs are considered diagnostically significant. To identify the latter, use:

• Ultrasound methods (ultrasound of the pelvic organs, kidneys and echocardiography).
• X-ray methods.
• Endoscopic methods (FGDS).
• Electrophysiological methods (EEG, ECG).
• Methods of laboratory diagnostics (biochemical and immunological blood tests).
• Skin biopsy.

If the diagnostics revealed violations from several main systems, this indicates with a high degree of certainty the development of CTD. Individuals diagnosed with CTD should be consulted by a geneticist.

Treatment

Both the diagnosis of this disease and its treatment are difficult. To date, no specific therapy for DST has been found. Patients are often registered with doctors of various specializations (traumatologists and gastroenterologists, oculists and cardiologists, neurologists and nephrologists, pulmonologists, hematologists and gynecologists).

If DST is mild, then treatment is not required. In this case, all doctors recommend paying attention to prevention:

• Lifestyle change.
• Rationalization of loads.
• Proper nutrition and ensuring that the body receives the proper amount of nutrients and substances that go to the construction of connective tissue.

Only the muscle system is capable of compensating for the insufficiency of ST development. Moreover, almost every muscle of the body should be trained and developed (not only external muscles, but also the myocardium, oculomotor muscles, etc.).

In the case of local changes and the slow development of the pathological process, treatment is recommended using measures that stimulate the compensatory mechanisms of the human body:

• Physiotherapy activities.
• Reflexology (acupuncture and massage).

Treatment of the disease is syndromic in nature and depends on the prevalence of symptoms.

Together with such therapy, metabolites (Elcarnitine, coenzyme Q10) can be prescribed.

Treatment of children

With an isolated form of the disease, the patient's quality of life usually does not decrease. If connective tissue dysplasia is detected in children, especially in an undifferentiated form, and all measures are taken to prevent the development of the disease, the compensation stage can last until old age. If several major systems are affected, the patient's quality of life deteriorates, the threat of disability and even life increases due to internal bleeding, aneurysm rupture, ischemic attacks, etc. In this case, therapy can even be surgical.

The syndrome of connective tissue dysplasia, identified in early childhood, should rather be attributed to structural features inherited than to a disease. But TDTS is a significant factor contributing to the development of a particular disease. The presence of SDST requires a certain approach to the organization of the child's lifestyle, his nutrition and leisure. A child with dysplastic syndrome must be adapted (if necessary, with the help of specialists) to the realities of this world. His self-esteem should not be low.

However, when choosing a profession, you should understand that a career as an athlete or a sedentary job is not the best choice. Gutta-percha children (with joint hypermobility syndrome) often become famous gymnastics athletes at the age of 10, but by the age of 15 they have serious joint diseases and require serious treatment.

Connective tissue, which makes up about 50% of the total body weight and holds together all the tissues of the body, is formed from the first days of the fetus's life. With a deficiency of the components from which the connective tissue is built, serious developmental anomalies occur. With a pronounced deficiency of "building materials" of the connective tissue, these anomalies are incompatible with life already in the prenatal period (missed pregnancy, etc.). With a less pronounced deficiency, the child is born viable, but is characterized by dysmorphisms and lower body weight and height.

Therefore, violations of the connective tissue structure (or connective tissue dysplasia, CTD) contribute to the development of a wide variety of diseases that seem to have nothing to do with pathology in children and adolescents: scoliosis and varicose veins, "school" myopia and nephroptosis, mitral valve prolapse and flat feet, as well as many others. It is obvious that all these diseases are united in some way by “weak”, insufficiently formed connective tissue. Mechanically weak connective tissue is the basis of morphofunctional changes not only in scoliosis, osteoporosis and other pathologies of cartilage and bone tissue, but also in cardiovascular and cerebrovascular diseases. Structural inferiority and reduced regenerative capacity of the connective tissue of the vessels determine the increase in the levels of chronic inflammation, the lower effectiveness of traditional treatment regimens, a longer recovery period, etc. .

Connective tissue differs from any other type of tissue in having an excess of extracellular matrix. The extracellular matrix consists of a ground substance (proteoglycans) mechanically reinforced with three types of fibers: 1) collagen fibers (consisting mainly of type I collagen), 2) flexible fibers (consisting mainly of elastin and fibrillins) and 3) reticular (or reticular) fibers. ) fibers (type III collagen). It should be noted that magnesium-dependent enzymes take part in the synthesis of these connective tissue components. In addition, magnesium regulates parathyroid hormone secretion, vitamin D metabolism and potentiates the effects of vitamin D in bone tissue, which is important for the treatment and prevention of vitamin D-resistant rickets. Therefore, magnesium deficiency provokes and exacerbates dysplastic processes in the connective tissue, worsening its strength and elasticity. The relationship between dysplastic processes in the connective tissue and magnesium deficiency is especially relevant in children who are constantly in a period of active growth.

Currently available data indicate that the incidence of CTD depends on the age of the examined individuals. Growth processes in children flow unevenly. There are several periods of the most intensive growth: the 1st year of life, the period of preparation for school (5-7 years), the period of the so-called teenage "jerk" (11-15 years). In each of these transitional periods, DST manifests itself in different ways. In the 1st year of life with DST, rickets, muscle hypotonia, and joint hypermobility are most often detected; in the period of preparation for school, myopia and flat feet often start; during the period of teenage "jerk" - scoliosis, deformities of the chest and spine, striae of the hips and abdomen, mitral valve prolapse. In adolescence, the increase in the number of signs of connective tissue dysmorphogenesis can be more than 300%.

It should be noted that the most intensive growth is observed in premature babies and children with low birth weight. These children constitute a risk group for the development of CTD. Given the early registration of such children, the doctor and his developing patient have a large reserve of time to organize a comprehensive rehabilitation program, including kinesitherapy, sports and good nutrition.

An adequate diet necessarily includes sufficient provision of the child with all micronutrients, which are the building materials of connective tissue. Taking into account the widespread distribution among children of dietary deficiencies of micronutrients, primarily magnesium, the need for the use of effective and safe preparations of organic magnesium becomes obvious. With DST, magnesium therapy courses should be long enough (at least 6 months).

About the diagnosis of DST

Connective tissue dysplasia is a genetically and nutritionally determined condition caused by disorders of connective tissue metabolism in the embryonic and postnatal periods and characterized by abnormalities in the structure of extracellular matrix components (fibers and ground substance) with progressive morphofunctional changes in various systems and organs.

Examination of the child by a neonatologist immediately after birth makes it possible to establish a number of characteristic phenotypic manifestations of CTD. Conventionally, they can be divided into groups depending on the localization of organs and systems involved in the dysplastic process. The individual signs listed below are not strictly specific for CTD and require clinical assessment and, if necessary, a clarifying differential diagnostic analysis.

1. Osteoarticular changes:

• asthenic type of constitution;
• dolichostenomelia;
• arachnodactyly;
• chest deformities (funnel-shaped and keeled);
• spinal deformities (scoliosis, straight back syndrome, hyperkyphosis, hyperlordosis, spondylolisthesis);
• skull deformities (acrocephaly, arched palate, micrognathia, crowding of teeth);
• limb deformities (valgus, varus);
• foot deformities (flat feet, hollow foot, etc.);
• joint hypermobility.

2. Skin and muscle changes:

• tensile skin;
• thin skin;
• flaccid skin;
• healing in the form of "tissue paper";
• keloid scars;
• hemorrhagic manifestations (ecchymosis, petechiae);
• muscle hypotonia and / or malnutrition;
• hernia.

3. Signs of DST of the organ of vision:

• myopia;
• flat cornea;
• subluxation (dislocation) of the lens.

4. Signs of DST of the cardiovascular system:

• prolapse of the heart valves;
• myxomatous degeneration of the valvular structures of the heart;
• dilatation of the fibrous rings of the heart;
• expansion of the aortic root;
• aneurysms of the interatrial, interventricular septum of the heart;
• expansion and aneurysms of blood vessels (aorta, pulmonary artery, cerebral arteries);
• varicose veins, phlebopathy.

5. Signs of DST of the bronchopulmonary system:

• tracheobronchomalacia, tracheobronchomegaly;
• tracheobronchial dyskinesia;
• bronchiectasis;
• apical bullae and primary spontaneous pneumothorax.

6. Signs of DST of the digestive system:

• motor-tonic disorders (refluxes);
• violations of the fixation of organs (gastroptosis, colonoptosis);
• changes in the size and length of hollow organs (megacolon, dolichosigma, etc.).

7. Signs of DST of the urinary system:

• nephroptosis, reflux.

8. Signs of DST of the blood system:

• thrombocytopathy, coagulopathy;
• hemoglobinopathies.

9. Signs of DST of the nervous system:

• vegetative dystonia.

It should be noted that in the International Classification of Diseases (ICD-10), undifferentiated variants of CTD are not included in a separate heading, which undoubtedly complicates the work of a practitioner. However, with careful work with the classification, you can find the appropriate code for any manifestation of DST. For example, the diagnoses "I34.1 Mitral valve prolapse", "I71.2 Aortic aneurysm and dissection", "I83 Varicose veins of the lower extremities" in the heading I00-99 "Diseases of the circulatory system" are clearly characterized by violations of the connective tissue structure. Other examples: "H52.1 Myopia", "H27.1 Subluxation (dislocation) of the lens", "K07 Malocclusion", "K40 Inguinal hernia", "K41 Femoral hernia", etc. Therefore, DST is by no means limited to diagnoses in heading M00-99 "Diseases of the musculoskeletal system and connective tissue" ("M35.7 Hypermobility syndrome", "M40.0 Positional kyphosis" and others).

Examination of patients with CTD is carried out in strict sequence, in accordance with the following tasks:

• detection of minor developmental anomalies and malformations;
• identification of phenotypic signs of CTD;
• differential diagnosis of syndromic and non-syndromic forms;
• assessment of the degree of progression of the flow;
• determination of the risk of developing complications of the course, the occurrence of associated pathology, sudden death;
• assessment of the degree of working capacity.

The search for phenotypic signs of CTD should be carried out during the physical examination purposefully and consistently. More detailed information on the diagnosis of CTD, which is extremely important for a practitioner, is given in the monograph by Nechaeva G.I. et al., 2010.

Molecular biological mechanisms of the relationship between DST and magnesium deficiency

Understanding the role of magnesium in maintaining the structure of connective tissue is inseparable from the molecular and cellular structure of connective tissue. In molecular biology, the extracellular matrix (ECM) is defined as a complex network formed by numerous structural macromolecules (proteoglycans, collagens, elastin). By interacting with each other and with cells, they maintain the structural integrity of tissues. The connective tissue shows an excess of ECM with a fairly small number of cells. It is the ECM that helps keep cells together and provides an organized environment within which migrating cells can move and interact with each other.

The extracellular matrix consists of fundamentally necessary components - the main substance, collagen, elastin fibers. The most important element of the ECM is the main substance formed by proteoglycans - extremely stretched polypeptide chains connected to numerous polysaccharide molecules of glycosaminoglycans through strong covalent bonds.

Numerous chains of proteoglycans are attached to a special type of glycosaminoglycan, a polymer of hyaluronic acid called hyaluronan. Threads of hyaluronan help to fasten the structure of the main substance into a single whole. This prevents compression and stretching of the ECM, and also ensures rapid diffusion of nutrients and hormones to the cells of the connective tissue. Hyaluronan is synthesized by hyaluronan synthetases (HAS1, HAS2 and HAS3 genes) and degraded by hyaluronidases (HYAL2, HYAL3, HYAL4 and HYALP genes). Hyaluronan synthetases HAS1, HAS2 and HAS3 contain a magnesium ion in the active site. Magnesium deficiency leads to a decrease in the activity of hyaluronan synthetases and, as a result, to a deterioration in the mechanical properties of hyaluronan filaments in the main substance of the extracellular matrix.

Enzymes involved in biochemical modifications and attachment of glycosaminoglycans can also significantly affect the structure of ECM. For example, a deficiency of xylosyl-beta-1,4-galactosyltransferase-7 (B4GALT7 gene) is associated with one of the forms of CTD - Ehlers-Danlos syndrome, which is manifested by a tendency to dislocation, the presence of fragile or hyperelastic skin, fragile vessels, etc. .

Collagen fibers give connective tissue strength and durability. Each collagen fiber is several micrometers in diameter and is made up of thousands of individual collagen polypeptide chains tightly packed together. It should be noted that connective tissue dysplasia most often occurs not so much due to genetic defects in collagen, but due to defects in dozens of genes that affect the biosynthesis, post-translational modifications, secretion, self-assembly and remodeling of collagen fibers. For example, lysyl oxidase (LOX gene), as well as lysyl oxidase-like enzymes (LOXL1, LOXL2, LOXL3, and LOXL4 genes) cross-link collagen polypeptide chains, thus enhancing the mechanical strength of fibrils. Lysyl oxidase activity deficiency is found in patients with Ehlers-Danlos syndrome.

Magnesium has been shown to reduce the activity of matrix metalloproteinases (MMPs) (Ueshima K., 2003). Accordingly, magnesium deficiency leads to an increase in the total activity of MMPs and a more aggressive degradation of collagen fibers, which also worsens the mechanical strength of the connective tissue. Experiments confirm the effect of magnesium on the biological activity of MMPs. In mice with artificially induced magnesium deficiency, the aortic wall is significantly thinner than in control animals. These changes correlate with an increase in the overall activity of MMP2 and MMP9 metalloproteinases. It is likely that the effect of magnesium in reducing MMP2 activity is blocked by two tyrosine kinase inhibitors, genistein and herbimycin. This suggests that extracellular magnesium reduces MMP secretion through an intracellular signaling cascade that turns on a specific tyrosine kinase. Supplementation of the diet with folic acid and magnesium salts reduces the secretion of MMP2 and has a positive effect, in particular, on the course and prognosis of coronary heart disease (CHD).

Cells (fibroblasts, chondroblasts, osteoblasts) are the active component of connective tissue. It is the cells that synthesize the elements of the extracellular matrix (proteoglycans, collagen, elastin fibers, fibronectin, etc.) and maintain the structural integrity of the connective tissue. The cells also secrete all the enzymes necessary for the formation and remodeling of connective tissue (metalloproteinases, etc.).

It should be noted the significant influence of microelements, in particular magnesium ions, on the processes of synthesis by connective tissue cells. In particular, Mg 2+ ions stabilize the structure of transfer RNA (tRNA), and magnesium deficiency leads to an increase in the number of dysfunctional tRNA molecules, thus reducing and slowing down the overall rate of protein synthesis. Studies have shown that low magnesium content stimulates premature death of endotheliocytes and fibroblasts in culture. Other possible mechanisms of the influence of magnesium are an increase in the activity of metalloproteinases elastase (degrading elastic fibers), transglutaminase (forming glutamine-lysine cross-links of elastin), lysyl oxidase (cross-linking of elastin and / or collagen chains), hyaluronidases (degrading hyaluronan). These mechanisms are summarized in Fig. one.

The positive effect of magnesium on the structure of connective tissue is confirmed by the results of our recent experimental study on models of wounds and burns. The results of an experimental study of the effects of an organic magnesium salt (magnesium lactate dihydrate) on the epithelialization of wounds and burns showed that oral intake of organic magnesium stimulates more effective and rapid wound healing compared to standard therapy with solcoseryl. According to the results of histological analyzes of scar tissues in various groups of animals, magnesium intake prevents excessive growth of collagen fibrils, promotes the growth of elastin fibers, an increase in the number of connective tissue fibroblasts and the formation of a full-fledged basic substance, which generally leads to an increase in the histological quality of the scar.

About DST therapy in children

The contribution of heredity to the development of a multifactorial disease, which includes CTD, is no more than 20%. The share of environmental impacts and the possibility of clinical medicine in improving health accounts for about 30%, and the main role (50%) in the development of the disease is the patient's lifestyle. From a clinical and prognostic point of view, non-syndromic dysplasias are divided into three distinct groups, which requires a differentiated approach to the implementation of treatment and prevention technologies (Fig. 2).

In the vast majority of cases, the main task of monitoring young patients is to maintain health and prevent the progression of dysplastic processes. The main approaches to the treatment of patients with CTD are rational diet therapy, metabolic therapy, physiotherapy, therapeutic massage, individually selected exercise therapy and swimming. In the absence of significant functional disorders, children with CTD are shown a general regimen with the correct alternation of work and rest, morning exercises, alternation of mental and physical activity, walks in the fresh air, good night sleep, short rest during the day are appropriate. Dynamic loads are preferred (swimming, walking, skiing, cycling, badminton, wushu gymnastics) and ballet and dance classes, group playing sports associated with a high probability of injury are inappropriate.

An important direction in the treatment of patients with CTD is rational diet therapy. Its main goal is to provide the body with a sufficient amount of micronutrients (vitamins, trace elements, vitamin-like substances, etc.) necessary to maintain a healthy metabolism of connective tissue. Diet therapy is supplemented by drug treatment using vitamin-mineral complexes and vitamin monoforms (vitamins D, C, etc.) and / or mineral preparations (monoforms of magnesium, zinc, copper, manganese, boron, etc.). Particularly noteworthy is the role of vitamins C, E, B 6 and D.

Among trace elements, magnesium, copper and manganese are especially important for maintaining the physiological metabolism of connective tissue. For the structure of connective tissue, the role of magnesium is extremely important, which is one of the main bioelements that provide physiological metabolism of connective tissue.

When correcting a deep magnesium deficiency, it is difficult to manage only with a diet and pharmacotherapy is often required. Studies of bioaccumulation with the use of various magnesium preparations gave reason to assert that the bioavailability of organic magnesium salts is almost an order of magnitude higher than that of inorganic ones. At the same time, organic magnesium salts are not only much better absorbed, but also easier to tolerate by patients. Inorganic magnesium salts often give dyspeptic complications, such as diarrhea, vomiting, abdominal cramps. Treatment is more effective if both magnesium and magnesia fixative (vitamins B 6, B 1, Glycine) are administered simultaneously.

Among the drugs used to correct magnesium deficiency, Magne B 6 is approved for use in pediatrics. The Magne B 6 form in the form of an oral solution is approved for use in children from the first year of life (body weight over 10 kg) at a dose of 1-4 ampoules per day. Tablets Magne B 6 and Magne B 6 Forte are allowed for children over 6 years old (body weight over 20 kg) at a dose of 4-6 tablets per day.

It should be emphasized that diet therapy in patients with CTD is an integral part of a comprehensive treatment program for the corresponding "main" manifestation of CTD in this patient. For example, in the case of mitral valve prolapse (MVP), orthostatic symptoms (postural hypotension and palpitations) can be reduced by increasing fluid and salt intake, wearing compression stockings, and in severe cases, taking mineralocorticoids. Reception of acetylsalicylic acid (75-325 mg / day) is indicated for patients with MVP with transient ischemic attacks in sinus rhythm and without thrombi in the left atrium. Antibiotics for the prevention of infective endocarditis in all manipulations accompanied by bacteremia are prescribed to patients with MVP, especially in the presence of mitral regurgitation, thickening of the valves, lengthening of the chords, dilatation of the left ventricle or atrium.

There are literature data on the effectiveness of magnesium preparations in primary MVP. It was shown that after six months of regular intake of an organic magnesium preparation, not only did the heart rate and blood pressure normalize, the number of episodes of rhythm disturbances decreased, but tremor and the depth of prolapse of the mitral valve cusps significantly decreased.

Conclusion

Connective tissue dysplasia combines such diseases of children and adolescents as scoliosis, rickets, flat feet, disorders of organ fixation (gastroptosis, nephroptosis, colonoptosis), mitral valve prolapse, myopia and others. It deserves special attention that CTD in childhood is the pathophysiological basis for the formation of cardiovascular and cerebrovascular diseases in adults. Thus, CTD in childhood predisposes to a reduction in life expectancy and deterioration in the quality of life in adulthood. The available data from fundamental and clinical medicine suggest that CTD is one of the clinical manifestations of primary magnesium deficiency. Therefore, the use of magnesium preparations can be considered as a means of pathogenetic treatment of CTD. The sooner nutritional support is started against the background of modern magnesium-deficient nutrition, the better.

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EN.MGP.12.01.08

A. G. Kalacheva*, **,Candidate of Medical Sciences
O. A. Gromova*, **,
N. V. Kerimkulova*, **,
A. N. Galustyan***,Candidate of Medical Sciences, Associate Professor
T. R. Grishina*, **,doctor of medical sciences, professor

* Russian Satellite Center of the UNESCO Institute for Trace Elements, Moscow
** GBOU VPO IGMA of the Ministry of Health and Social Development of Russia, Ivanovo
*** GBOU VPO SZGMU them. I. I. Mechnikova of the Ministry of Health and Social Development of Russia, St. Petersburg

- a group of clinically polymorphic pathological conditions caused by hereditary or congenital defects in collagen synthesis and accompanied by impaired functioning of internal organs and the musculoskeletal system. Most often, connective tissue dysplasia is manifested by a change in body proportions, bone deformities, joint hypermobility, habitual dislocations, hyperelastic skin, valvular heart disease, vascular fragility, and muscle weakness. Diagnosis is based on phenotypic features, biochemical parameters, biopsy data. Treatment of connective tissue dysplasia includes exercise therapy, massage, diet, drug therapy.

Causes of connective tissue dysplasia

The development of connective tissue dysplasia is based on a defect in the synthesis or structure of collagen, protein-carbohydrate complexes, structural proteins, as well as essential enzymes and cofactors. The direct cause of the pathology of the connective tissue under consideration is various kinds of effects on the fetus, leading to a genetically determined change in the fibrillogenesis of the extracellular matrix. Such mutagenic factors include unfavorable environmental conditions, malnutrition and bad habits of the mother, stress, aggravated pregnancy, etc. Some researchers point to the pathogenetic role of hypomagnesemia in the development of connective tissue dysplasia, based on the detection of magnesium deficiency in the spectral study of hair, blood, oral fluid .

The synthesis of collagen in the body is encoded by more than 40 genes, for which more than 1300 types of mutations have been described. This causes a variety of clinical manifestations of connective tissue dysplasia and complicates their diagnosis.

Classification of connective tissue dysplasia

Connective tissue dysplasia is divided into differentiated and undifferentiated. Differentiated dysplasias include diseases with a defined, established pattern of inheritance, a clear clinical picture, known gene defects, and biochemical abnormalities. The most typical representatives of this group of hereditary connective tissue diseases are Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, mucopolysaccharidoses, systemic elastosis, dysplastic scoliosis, Beals syndrome (congenital contracture arachnodactyly), etc. The group of undifferentiated connective tissue dysplasias consists of various pathologies whose phenotypic signs do not correspond to any of the differentiated diseases.

According to the degree of severity, the following types of connective tissue dysplasia are distinguished: small (in the presence of 3 or more phenotypic signs), isolated (with localization in one organ) and actually hereditary diseases of the connective tissue. Depending on the prevailing dysplastic stigmas, 10 phenotypic variants of connective tissue dysplasia are distinguished:

1. Marfan-like appearance (includes 4 or more phenotypic signs of skeletal dysplasia).
2. Marfan-like phenotype (incomplete set of features of Marfan's syndrome).
3. MASS phenotype (includes involvement of the aorta, mitral valve, skeleton, and skin).
4. Primary mitral valve prolapse (characterized by echocardiographic signs of mitral prolapse, changes in the skin, skeleton, joints).
5. Classic Ehlers-like phenotype (incomplete set of features of Ehlers-Danlos syndrome).
6. Hypermobility Ehlers-like phenotype (characterized by hypermobility of the joints and associated complications - subluxations, dislocations, sprains, flat feet; arthralgias, involvement of bones and skeleton).
7. Joint hypermobility is benign (includes increased range of motion in the joints without skeletal involvement and arthralgia).
8. Undifferentiated connective tissue dysplasia (includes 6 or more dysplastic stigmas, which, however, are not enough to diagnose differentiated syndromes).
9. Increased dysplastic stigmatization with predominant bone-articular and skeletal features.
10. Increased dysplastic stigmatization with predominant visceral signs (small anomalies of the heart or other internal organs).

Since the description of differentiated forms of connective tissue dysplasia is given in detail in the corresponding independent reviews, in the future we will focus on its undifferentiated variants. In the case when the localization of connective tissue dysplasia is limited to one organ or system, it is isolated. If connective tissue dysplasia manifests itself phenotypically and involves at least one of the internal organs, this condition is considered as a syndrome of connective tissue dysplasia.

Symptoms of connective tissue dysplasia

External (phenotypic) signs of connective tissue dysplasia are represented by constitutional features, anomalies in the development of bones of the skeleton, skin, etc. Patients with connective tissue dysplasia have an asthenic constitution: tall, narrow shoulders, and underweight. Disturbances in the development of the axial skeleton can be represented by scoliosis, kyphosis, funnel-shaped or keeled deformities of the chest, juvenile osteochondrosis. Craniocephalic stigmas of connective tissue dysplasia often include dolichocephaly, malocclusion, dental anomalies, gothic palate, nonunion of the upper lip and palate. The pathology of the osteoarticular system is characterized by O-shaped or X-shaped deformation of the limbs, syndactyly, arachnodactyly, joint hypermobility, flat feet, a tendency to habitual dislocations and subluxations, bone fractures.

On the part of the skin, there is increased extensibility (hyperelasticity) or, on the contrary, fragility and dryness of the skin. Often, striae, age spots or foci of depigmentation, vascular defects (telangiectasias, hemangiomas) appear on it for no apparent reason. The weakness of the muscular system in connective tissue dysplasia causes a tendency to prolapse and prolapse of internal organs, hernias, and muscular torticollis. Other external signs of connective tissue dysplasia may include microanomalies such as hypo- or hypertelorism, protruding ears, ear asymmetry, low hairline on the forehead and neck, etc.

Visceral lesions occur with the interest of the central nervous system and the autonomic nervous system, various internal organs. Neurological disorders associated with connective tissue dysplasia are characterized by vegetative-vascular dystonia, asthenia, enuresis, chronic migraine, speech impairment, high anxiety and emotional instability. The syndrome of connective tissue dysplasia of the heart may include mitral valve prolapse, open foramen ovale, hypoplasia of the aorta and pulmonary trunk, elongation and excessive mobility of the chordae, aneurysms of the coronary arteries or the interatrial septum. The consequence of the weakness of the walls of the venous vessels is the development of varicose veins of the lower extremities and small pelvis, hemorrhoids, varicocele. Patients with connective tissue dysplasia tend to develop arterial hypotension, arrhythmias, atrioventricular and intraventricular blockades, cardialgia, and sudden death.

Cardiac manifestations are often accompanied by bronchopulmonary syndrome, characterized by the presence of cystic lung hypoplasia, bronchiectasis, bullous emphysema, repeated spontaneous pneumothoraxes. Characterized by damage to the gastrointestinal tract in the form of prolapse of internal organs, diverticula of the esophagus, gastroesophageal reflux, hiatal hernia. Typical manifestations of the pathology of the organ of vision in connective tissue dysplasia are myopia, astigmatism, hyperopia, nystagmus, strabismus, subluxation and dislocation of the lens.

On the part of the urinary system, nephroptosis, urinary incontinence, renal anomalies (hypoplasia, doubling, horseshoe-shaped kidney), etc. can be noted. Reproductive disorders associated with connective tissue dysplasia in women can be represented by prolapse of the uterus and vagina, metro- and menorrhagia, spontaneous abortions, postpartum hemorrhage; in men, cryptorchidism is possible. Persons with signs of connective tissue dysplasia are prone to frequent echocardiography, ultrasound of the kidneys, ultrasound of the abdominal organs), endoscopic (EGD), electrophysiological (ECG, EEG), radiological (radiography of the lungs, joints, spine, etc.) methods. Identification of characteristic multiple organ disorders, mainly from the musculoskeletal, nervous and cardiovascular systems, with a high degree of probability indicates the presence of connective tissue dysplasia.

In addition, biochemical parameters of blood, the hemostasis system, immune status are examined, a skin biopsy is performed. As a method of screening diagnostics of connective tissue dysplasia, it is proposed to study the papillary pattern of the skin of the anterior abdominal wall: the identification of an unformed type of papillary pattern serves as a marker of dysplastic disorders. Families with cases of connective tissue dysplasia are advised to undergo medical genetic counseling.

Treatment and prognosis of connective tissue dysplasia

There is no specific treatment for connective tissue dysplasia. Patients are advised to adhere to a rational regimen of the day and nutrition, health-improving physical activity. In order to activate compensatory-adaptive capabilities, courses of exercise therapy, massage, balneotherapy, physiotherapy, acupuncture, osteopathy are prescribed.

In the complex of therapeutic measures, along with syndromic drug therapy, metabolic preparations (L-carnitine, coenzyme Q10), calcium and magnesium preparations, chondroprotectors, vitamin-mineral complexes, antioxidant and immunomodulating agents, herbal medicine, psychotherapy are used.

The prognosis of connective tissue dysplasia largely depends on the severity of dysplastic disorders. In patients with isolated forms, quality of life may not be impaired. Patients with polysystemic lesions have an increased risk of early and severe disability, premature death, the causes of which may be ventricular fibrillation, pulmonary embolism, aortic aneurysm rupture, hemorrhagic stroke, severe internal bleeding, etc.