home All hormones How can connective tissue dysplasia threaten a child’s health? Undifferentiated connective tissue dysplasia

How can connective tissue dysplasia threaten a child’s health? Undifferentiated connective tissue dysplasia

Phenotypic signs of connective tissue dysplasia:

constitutional features (asthenic physique, lack of mass);
DST syndrome itself (developmental anomalies facial skull and skeleton, limbs, including kyphoscoliosis, deformation chest, joint hypermobility, skin hyperelasticity, flat feet);
minor developmental anomalies, which in themselves have no clinical significance, but act as stigmas.

A close relationship has been established between the number of external hair dryers, the severity of external dysplastic disorders and changes in the connective tissue framework internal organs- internal phenotypic signs of the syndrome.

One of important signs undifferentiated dysplasia connective tissue- asthenic physique, characterized by its combination with bone deformities and joint hypermobility. Thinning, hyperelasticity, vulnerability of the skin, areas of depigmentation and subatrophy are noted. When examining the cardiovascular system, a systolic murmur is often detected. Half of the patients are diagnosed with disorders heart rate, more often - blockade of the right bundle branch and extrasystole. ECG reveals valve prolapses, aneurysms interatrial septum and sinuses of Valsalva, enlargement of the aortic root and so-called minor cardiac anomalies: additional chords in the cavity of the left ventricle, dystonia of the papillary muscles. Heart damage usually has a relatively benign course.

There is a definite connection between the number and severity of phenes of undifferentiated connective tissue dysplasia and the number of minor cardiac anomalies. A generalized form of undifferentiated connective tissue dysplasia should be called cases in which it is possible to identify signs of clinically significant involvement of 3 or more organs and systems in the defect.

A frequent combination of inferiority of the connective tissue structures of the heart with deviations in the functioning of the autonomic nervous system has been noted. Frequent symptoms- psychovegetative disorders: increased level of anxiety, emotional instability. In children with undifferentiated connective tissue dysplasia with rhythm and conduction disturbances, the autonomic dysfunction syndrome occurs predominantly of the vagotonic type, in the form of syncope and asthenic conditions, cardialgia, tension headaches and is often accompanied by psychopathological disorders. According to cardiointervalography data, almost all children with cardiac dysregulation have manifestations of autonomic dysregulation, which indicates a decrease in the ability to adapt. As the DST syndrome increases, changes in personal and characterological characteristics are observed, reflecting an increased tendency to mental maladjustment.

Tracheobronchial dyskinesia is registered in some cases due to impaired elasticity of the trachea and bronchi; the obstructive syndrome is severe and long-lasting.

The gastrointestinal tract, as one of the richest in collagen in DST, is involved in the pathological process, which is manifested by intestinal microdiverticulosis, impaired excretion of digestive juices and peristalsis. In almost all patients with hereditary connective tissue diseases, superficial inflammatory changes in the gastric mucosa, pathological reflux in combination with Helicobacter colonization, and impaired gastric motility are detected.

From the urinary system diagnostic value have nephroptosis, increased kidney mobility, pyelectasia, kidney duplication, orthostatic proteinuria, increased excretion of hydroxyproline and glycosaminoglycans.

The clinical picture shows hemorrhagic syndrome due to platelet disorders and decreased synthesis of von Willebrand factor. Frequent nosebleeds, petechial-spotted rashes on the skin, bleeding gums, and prolonged bleeding from cuts. The development of hemorrhagic syndrome is associated not only with the inferiority of vascular connective tissue, but also with the failure of the contractile apparatus of platelets and is associated with autonomic disorders. These changes are often combined with the development of leuko- and thrombocytopenia, with disorders of platelet hemostasis, and inadequate coagulation. Violations of immunological competence due to dystrophic changes in thymolymphoid tissue are common. Characterized by a large number of foci chronic infection. In DST, a tendency of patients to develop autoimmune processes was discovered.

Neurological pathology is detected in the majority of sick children (vertebrobasilar insufficiency due to instability or dysplasia cervical region spine, juvenile osteochondrosis, spina bifida, intracranial hypertension, migraines, thermoregulation disorders). In children of puberty, a transformation of symptoms occurs; the main target organs are the spine and the organ of vision.

The process of unifying medical terminology led to the approval of the international term “hypermobility syndrome”. Although this term does not exhaust the variety of combinations of non-inflammatory connective tissue lesions, today it must be considered successful. The advantages of the term are the identification of generalized joint hypermobility as the most characteristic and easily defined clinical sign of this group of diseases, and the absence of the word “joint” in the definition directs the doctor to extra-articular (systemic) manifestations of the syndrome. An important reason What led to the adoption of this name by the international medical community was the development of criteria for the diagnosis of hypermobility syndrome and the existence of a simple scoring system (Beighton scale) that allows assessing the presence of generalized hypermobility. A standard examination of arthrological patients (x-ray of the affected joint, blood test for acute phase indicators) does not reveal any signs of pathology. The key to diagnosis is identifying joint hypermobility while excluding other rheumatic diseases (the latter is a prerequisite). It must be remembered that a person with hypermobility can develop any other joint disease.

Recognizing generalized joint hypermobility (Beighton P.)

Maximum points - 9

The degree of joint mobility has a normal distribution in the population. Joint hypermobility is observed in approximately 10% of people, only in a small proportion of them it is pathological. The presence of hypermobility can often be identified in blood relatives (mostly with similar problems). In 75% of cases the onset clinical manifestations falls on school age, the most common option is arthralgia of the knee joints. Increased range of motion reduces joint stability and increases the incidence of dislocation.

Hypermobility is the result of weakness and stretchability of ligaments, which are hereditary. Of particular importance in this regard are the genes encoding the synthesis of collagen, elastin, fibrillin and tenaskin. Clinical significance is determined by frequent dislocations and subluxations, arthralgia, and autonomic dysfunction. Thus, the formula of R. Graham (2000) helps to understand the relationship between joint hypermobility and joint hypermobility syndrome:

Joint hypermobility + Symptoms = Hypermobility syndrome.

With mechanical overload against the background of reduced resistance of cartilage and other connective tissue structures, areas of micronecrosis and inflammation (arthritis with synovitis or bursitis), stress arthropathy with dysplasia of the osteochondral apparatus can occur. Most patients suffer from non-inflammatory joint diseases (arthrosis, chronic diseases of the spine).

Characteristic signs of stress arthropathy:

familial forms of early osteoarthritis or osteochondrosis;
a history of injuries and ruptures of ligaments, joints, subluxations, joint and bone pain;
connection between pain and physical activity;
low activity of inflammation, it subsides as loads decrease, rapid relief of pain and restoration of movements;
damage to one or two joints along the axis;
limited effusion;
presence of local joint pain;
the presence of osteoporosis, joint hypermobility and other signs of connective tissue dysplasia.

Still, patients with “blurred” signs of UCTD are more often encountered. Identification of phenotypic signs of UCTD in combination with the above manifestations should lead the doctor to think about the possibility of a clinically significant systemic connective tissue defect.

Diagnostic signs of connective tissue dysplasia revealed during examination

	Slow healing of wounds and scars Joint pain Pain in the spine Cardialgia Feeling short of air Increased fatigue Bruising, nosebleeds, vascular-platelet type bleeding
General inspection	Body length >95th centile Arm span to body length ratio >1.03 Hernias, muscle diastases Asthenic physique Hypoplasia of muscle and adipose tissue
	Atrophic striae, visible vasculature Increased skin extensibility Foci of depigmentation Dark spots Hypertrichosis Hemangiomas, angioectasia Ecchymosis, positive pinch test Dry wrinkled skin Transverse folds on the abdomen
	Dolichocephaly, skull asymmetry Long or short neck Anomalies ears (low position and asymmetry; abnormal development curls; small or attached earlobes; large, small or protruding ears) High or Gothic palate Split tongue Malocclusions Striations of the tongue Disturbed growth of teeth and their anomalies Deviated nasal septum
Torso	Deformation of the chest (funnel-shaped, keeled, decreased anteroposterior size) Scoliosis due to dysplasia ligamentous apparatus Thoracic lordosis
	Wide or close eyes Short or narrow palpebral fissures Eye pathology (lens luxation, keratoconus, anisocoria, blue sclera, colobomas) Slanted chin Small or large mouth
	Joint hypermobility (hyperextension, positive thumb sign) Long fingers, positive thumb symptoms Thickening of the nail phalanges, syn-, polydactyly, impaired nail growth Short or crooked little fingers IV finger is shorter than II
	Increased foot length, flat feet Joint hypermobility (hyperextension of the knee joints, flexion of the foot >45") Vein dilatation, venous valve insufficiency Habitual dislocations and subluxations of joints Sandal-shaped gap X- and O-shaped curvature of the legs

Note. Each hair dryer is scored from 0 to 3 points depending on its severity (0 - no hair dryer; 1 - insignificant; 2 - average; 3 - significant severity of the phenotypic trait). Children with a score of more than 30 have a diagnostically significant set of signs of CTD. When calculating, only the points obtained during an objective examination are evaluated. A score of more than 50 allows one to think about differentiated DST.

The most numerous complaints were related to cardiac and autonomic symptoms. The structure of symptoms of the disease was dominated by headaches (28.6%), recurrent bronchial obstruction (19.3%), cough (19.3%), difficulty in nasal breathing (17.6%), abdominal pain (16.8%). ), skin rashes (12.6%), joint pain (10,9%), increased fatigue(10.9%), low-grade fever (10.1%).

In the structure of the main diagnoses, noteworthy is the high frequency allergic diseases identified in 25.2% of children (the majority was bronchial asthma - 18.5% of the group); the second most common was neurocirculatory dysfunction - 20.2%. In third place were diseases of the musculoskeletal system and connective tissue, identified in 15.1% (DST accounted for 10.9% of the group). Digestive diseases were found in 10.1% of children. All children had concomitant diagnoses, the vast majority - more than one. Diseases of the musculoskeletal system and connective tissue were present in 37.0%, UCTD was present in 19.3%, infectious diseases respiratory organs - in 27.7%, allergic - in 23.5%, gastrointestinal diseases - in 20.2%, nervous system - in 16.8%.

ECG features were identified in 99.1% (an average of 2.2 ECG phenomena per child). Metabolic disorders- in 61.8%, rVica bundle branch block - in 39.1%, sinus arrhythmia - in 30.1%, ectopic rhythm - in 27.3%, electrical position shift - in 25.5%, early ventricular repolarization syndrome - in 24.5%, displacement electrical axis to the right - 20.0%. EchoCG revealed minor cardiac anomalies in 98.7% (an average of 1.8 per child). The most common anomalies were the presence of chordae in the cavity of the left ventricle (60.0%), mitral valve prolapse I degree (41.9%), tricuspid valve prolapse I degree (26.7%), prolapse of the pulmonary valves (10.7% ), dilatation of the sinuses of Valsalva (10.7%), which significantly exceeds the population frequency of findings on EchoCG.

Ultrasound of the gastrointestinal tract revealed changes in 37.7% (an average of 0.72 findings per person examined). Deformation gallbladder- in 29.0%, accessory lobes of the spleen - in 3.5%, increased echogenicity of the pancreas and gallbladder wall, dyscholia, hypotension of the gallbladder - 1.76% each, respectively, other changes - in 7.9%. Kidney ultrasound revealed abnormalities in 23.5% of children (an average of 0.59 findings). Kidney hypermotility was detected in 6.1%, pyeloectasia in 5.2%. doubling collecting system and nephroptosis - 3.5% each, hydronephrosis - 2.6%, other changes - 7%.

Neurosonography abnormalities were detected in 39.5% (0.48 per person examined): bilateral dilatation of the lateral ventricles - in 19.8%, their asymmetry - in 13.6%, unilateral dilatation - in 6.2%, other changes - in 8.6%. X-ray and ultrasound revealed a high frequency of disorders in the cervical spine (81.4%, on average 1.63 per person examined): instability was detected in 46.8%, scoliosis of the cervical spine - in 44.1%, cranial subluxation C, C 2 - in 22.0%, hypoplasia C - in 18.6%, Kimmerli anomaly - in 15.3%, other changes - in 17.0% of children. Ultrasound Dopplerography of the main vessels of the head revealed disturbances in 76.9% (1.6 findings per person examined). Asymmetry of blood flow vertebral arteries detected in 50.8%, in the internal carotid arteries - in 32.3%, in the common carotid arteries - in 16.9%, asymmetry of outflow through the jugular veins - in 33.8%, other disorders - in 23.1%. When recording platelet aggregation function, disorders were detected in 73.9% of children, the average values for the group were lower than the reference values.

Thus, the results of the examination can be characterized as multiple organ disorders, most often of the cardiovascular, nervous, and musculoskeletal systems. In addition to the complex of phenotypic signs of CTD, each child had signs of several disorders of organs and systems: ECG changes, minor cardiac anomalies, changes in the cervical spine and blood flow asymmetry, structural features of internal organs, decreased BMD. On average, a child has more than 8 particular features (4 - from the heart; 1.3 - from the organs abdominal cavity; 3.2 - from the side of the cervical vertebrae and vessels). Some of them can be classified as functional (changes in the ECG, the presence of blood flow asymmetries on Doppler ultrasound, instability of the cervical spine, deformation of the gallbladder), others are morphological in nature (hypoplasia and subluxation of the cervical vertebrae, minor cardiac anomalies, decreased BMD).

A decrease in BMD may be important in the formation of early osteochondrosis, scoliosis, and blood supply disorders in the cervical spine. UCTD plays a major etiological role in the genesis of neurocirculatory dysfunction in children. The initial background for its formation is the weakness of the subendothelial layer of blood vessels, developmental anomalies and weakening of the ligamentous apparatus of the vertebrae. As a result, hemorrhages and injuries to the cervical spine are common during childbirth. The processes of bone remodeling and bone formation are 75-85% under genetic control. Urgent attempts to reduce the avalanche of bone fractures in old age (2/3 of them at this age are vertebral and femoral) should begin in adolescence and aim at preventing late osteoporosis.

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’ life. With a deficiency of the components from which connective tissue is built, serious developmental anomalies occur. With a pronounced deficiency of “building materials” of connective tissue, these anomalies are incompatible with life already in the prenatal period (frozen pregnancy, etc.). With a less pronounced deficiency, the child is born viable, but is characterized by dysmorphisms and lower body weight and height.

Therefore, disorders of the connective tissue structure (or connective tissue dysplasia, DST) 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 vascular connective tissue determine increased levels of chronic inflammation, less effectiveness of traditional treatment regimens, a longer recovery period, etc.

Connective tissue is distinguished from any other type of tissue by its excess extracellular matrix. The extracellular matrix consists of a ground substance (proteoglycans) mechanically reinforced by 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 (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 the secretion of parathyroid hormone, the metabolism of vitamin D 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 aggravates dysplastic processes in connective tissue, impairing its strength and elasticity. The relationship between dysplastic processes in 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 individuals examined. The growth process in children is uneven. There are several periods of the most intense growth: the 1st year of life, the period of preparation for school (5-7 years), the period of the so-called teenage “spurt” (11-15 years). In each of these transition periods, DST manifests itself differently. In the 1st year of life with DST, rickets, muscle hypotonia, and joint hypermobility are most often detected; during the period of preparation for school, myopia and flat feet often start; during the period of adolescence, scoliosis, deformities of the chest and spine, stretch marks of the thighs 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 maximum intensive growth observed in premature and low birth weight infants. These children constitute a risk group for the development of CTD. Considering 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 kinesiotherapy, 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 occurrence of dietary micronutrient deficiencies among children, primarily magnesium, the need to use effective and safe organic magnesium preparations becomes obvious. For DST, courses of magnesium therapy should be quite long (at least 6 months).

About the diagnosis of DST

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

Examination of the child by a neonatologist immediately after birth allows us to establish a number of characteristic phenotypic manifestations DST. 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 DST and require clinical assessment and carrying out, if necessary, a clarifying differential diagnostic analysis.

1. Bone and joint changes:

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

2. Skin and muscle changes:

stretchable skin;
thin skin;
flaccid skin;
"tissue paper" healing;
keloid scars;
hemorrhagic manifestations(ecchymoses, petechiae);
muscle hypotonia and/or malnutrition;
hernias

3. Signs of DTD of the organ of vision:

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

4. Signs of DST of the cardiovascular system:

heart valve prolapse;
myxomatous degeneration of cardiac valve structures;
dilatation of the fibrous rings of the heart;
expansion of the aortic root;
interatrial aneurysm, interventricular septum hearts;
dilation 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 organ fixation (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 DTD of the nervous system:

vegetative-vascular dystonia.

It should be noted that in International classification diseases (ICD-10), undifferentiated variants of DST are not identified in a separate section, which undoubtedly complicates the work of a practicing physician. However, if you carefully 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 Aneurysm and aortic dissection”, “I83 Varicose veins of the lower extremities” in the heading I00-99 “Diseases of the circulatory system” are clearly characterized by disorders of the connective tissue structure. Other examples: “H52.1 Myopia”, “H27.1 Lens subluxation”, “K07 Malocclusion”, “K40” Inguinal hernia”, “K41 Femoral hernia”, etc. Therefore, DST is by no means limited to diagnoses in the heading M00-99 “Diseases of the musculoskeletal system and connective tissue” (“M35.7 Hypermobile syndrome”, “M40.0 Positional kyphosis” and other).

The examination of patients with DST is carried out in strict sequence, in accordance with the following tasks:

identification of minor developmental anomalies and malformations;
identification of phenotypic signs of DST;
differential diagnosis syndromic and non-syndromic forms;
assessment of the degree of progression of the flow;
determining the risk of developing complications of the course, the occurrence of associated pathologies, sudden death;
assessment of the degree of ability to work.

The search for phenotypic signs of DST should be carried out purposefully and consistently during a physical examination. More detailed information on the diagnosis of DST, which is extremely important for a practicing doctor, 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 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. Connective tissue exhibits excess 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 ECM is the main substance formed by proteoglycans - extremely elongated polypeptide chains connected to numerous polysaccharide glycosaminoglycan molecules through strong covalent bonds.

Numerous chains of proteoglycans are attached to a special type of glycosaminoglycan - a polymer hyaluronic acid, called hyaluronan. Threads of hyaluronan help hold the structure of the main substance together into a single whole. This prevents compression and stretching of the ECM, and also ensures rapid diffusion nutrients and hormones to connective tissue cells. Hyaluronan is synthesized through hyaluronan synthetases (genes HAS1, HAS2 and HAS3) and degraded through hyaluronidases (genes HYAL2, HYAL3, HYAL4 and HYALP). 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 consequence, to a deterioration in the mechanical properties of hyaluronan filaments in the ground substance of the extracellular matrix.

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

Collagen fibers give connective tissue strength and durability. Each collagen fiber is several micrometers in diameter and consists 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 rather due to defects in dozens of genes affecting 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, thereby increasing the mechanical strength of fibrils. Deficiency of lysyl oxidase activity is found in patients with Ehlers-Danlos syndrome.

Magnesium has been shown to help reduce the activity of matrix metalloproteinases (MMPs) (Ueshima K., 2003). Accordingly, magnesium deficiency leads to an increase in the total activity of MMPs and more aggressive degradation of collagen fibers, which also worsens the mechanical strength of connective tissue. Experiments confirm the influence of magnesium on the biological activity of MMP. 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 the metalloproteinases MMP2 and MMP9. 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 involves a specific tyrosine kinase. Diet supplement 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) - active ingredient 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, thereby reducing and slowing down the overall rate of protein synthesis. Studies have shown that low magnesium levels stimulate premature death endothelial cells and fibroblasts in culture. Other possible mechanisms of magnesium's influence are an increase in the activity of metalloproteinases-elastases (degrading elastic fibers), transglutaminase (forming cross-links of glutamine-lysine in elastin), lysyl oxidase (cross-linking of elastin and/or collagen chains), hyaluronidases (degrading hyaluronan). These mechanisms are summarized in Fig. 1.

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 organic magnesium salt (magnesium lactate dihydrate) on the epithelialization of wounds and burns showed that oral magnesium intake stimulates more effective and fast healing wounds compared to standard therapy with solcoseryl. According to the results histological analyzes scar tissue 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 ground 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 DST, is no more than 20%. The share of environmental influences and the possibility of clinical medicine in improving health accounts for about 30%, and the patient’s lifestyle plays a major role (50%) in the development of the disease. From a clinical and prognostic point of view, nonsyndromic dysplasias are divided into three clearly distinguishable groups, which requires a differentiated approach to the implementation of treatment and preventive technologies (Fig. 2).

In the vast majority of cases, the main task of monitoring patients young— maintaining health and preventing the progression of dysplastic processes. The main approaches to treating patients with DST are rational diet therapy, metabolic therapy, physiotherapy, therapeutic massage, individually selected physical therapy and swimming. In the absence of significant functional impairments, 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 on fresh air, a full night's sleep, short rest during the day. Dynamic loads are preferable (swimming, walking, recreational skiing, cycling, badminton, wushu gymnastics) and ballet and dance classes, group sports associated with a high probability of injuries are inappropriate.

An important area of treatment for patients with DST is rational diet therapy. Its main goal is to provide the body with sufficient amounts of micronutrients (vitamins, microelements, vitamin-like substances, etc.) necessary to maintain healthy connective tissue metabolism. Diet therapy is complemented drug treatment using vitamin-mineral complexes and monoforms of vitamins (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, B6 and D.

Among the 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 ensure the physiological metabolism of connective tissue.

When correcting deep magnesium deficiency It is difficult to cope with diet alone and pharmacotherapy is often required. Studies of bioaccumulation when using various magnesium preparations have given grounds 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 more often cause dyspeptic complications, such as diarrhea, vomiting, and abdominal cramps. Treatment is more effective if both magnesium and a magnesium fixative (vitamins B6, B1, Glycine) are administered simultaneously.

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

It should be emphasized that diet therapy in patients with DST is integral part comprehensive treatment program for the corresponding “main” manifestation of DST in of 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 garments, and in severe cases, taking mineralocorticoids. 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 during all procedures accompanied by bacteremia are prescribed to patients with MVP, especially in the presence of mitral regurgitation, thickening of the leaflets, lengthening of the chords, dilatation of the left ventricle or atrium.

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

Conclusion

Connective tissue dysplasia unites such diseases of children and adolescents as scoliosis, rickets, flat feet, organ fixation disorders (gastroptosis, nephroptosis, colonoptosis), mitral valve prolapse, myopia and others. Particularly noteworthy is the fact that CTD in childhood is the pathophysiological basis for the formation of cardiovascular and cerebrovascular diseases in adults. Thus, CTD in childhood predisposes to shortened life expectancy and worse quality of life in adulthood. Available data from basic and clinical medicine suggest that DST is one of clinical forms manifestations of primary magnesium deficiency. Therefore, the use of magnesium preparations can be considered as a means of pathogenetic treatment of DST. The earlier nutritional support is started against the background of modern magnesium-deficient nutrition, the better.

Literature

RU.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 of Trace Elements, Moscow
** GBOU VPO IGMA Ministry of Health and Social Development of Russia, Ivanovo
*** GBOU VPO Northwestern State Medical University named after. I. I. Mechnikova Ministry of Health and Social Development of Russia, Saint Petersburg

The child often gets sick, is treated by doctors of different specialties and everyone finds a pathology. Genetic consultation is required. Connective tissue dysplasia in children is a common disease, affecting 50% of schoolchildren. The causes, diagnosis, treatment have not been sufficiently studied. Many doctors believe that pathology occurs in embryonic development.

Causes of the disease

Connective tissue dysplasia syndrome is damage to the structure, disruption of the functioning of organs and systems of the body due to genetically determined improper synthesis of proteins. The disease begins in the prenatal period and is a consequence of the following harmful effects on the body of a pregnant woman:

Work involving any type of radiation.
Smoking, drinking alcohol.
Food products with various chemical additives.
Medications, cosmetical tools, the effect of which on pregnant women has not been studied.
Bad ecology.
Various diseases during pregnancy.

Types of connective tissue dysplasia in children

A well-studied isolated pathology, with a clearly defined clinical picture, known gene defects, and proven treatment methods, constitutes a group of differentiated dysplasias. These diseases are rare and can be easily diagnosed using genetic methods. Combinations of symptoms and syndromes with an uncertain mechanism of gene damage and the absence of a unified clinical picture are undifferentiated dysplasia. It occurs much more often, diagnosis is difficult due to the large number of symptoms.

Differentiated dysplasia

Diseases with a studied mechanism of development, clinical picture, diagnostic methods, treatment. These include:

Marfan syndrome is characterized by the presence of long fingers on the patient's hands.

Marfan syndrome. Characterized by tall stature, long fingers, visual and cardiovascular disorders.
Ehlers-Danlos disease. Affects the skin, joints, small vessels.
Stickler syndrome. Causes diseases of the eyes, joints, and muscle tissue.
Osteogenesis imperfecta, increased bone fragility.

Undifferentiated dysplasia

Systemic pathology of connective tissue, the gene defects of which are poorly studied, treatment is carried out by specialists from various medical specialties, taking into account the localization of the pathology. Main syndromes:

asthenic - muscle weakness, fatigue, depression;
minor cardiac anomalies - mitral valve disease, arrhythmia;
thoracic - keeled, funnel-shaped chest, spinal curvature;
- pathological mobility of bone joints.

Symptoms of dysplasia

The presence of connective tissue in all organs causes a large polymorphism in the clinical manifestations of the disease. The patients' complaints are of a general nature and are not specific to dysplasia, including weakness, fatigue, and headaches. The examination begins with measuring height and limb length. Conduct clinical tests:

When performing the test, the thumb easily extends beyond the palm when placed across it.

Thumb The brush is placed across the palm, with the nail protruding beyond its edge.
The little finger easily bends 90 degrees towards the forearm.
The patient, with fixed feet, reaches the floor with the entire plane of the palms, without bending the knees.
With the first and fifth fingers, the child clasps the wrist of the other hand.

Valuable information is obtained when examining a patient. In this case, the pediatrician already at the first examination reveals:

asthenic body type;
keeled chest deformity;
rachiocampsis;
depression of the sternum - “shoemaker's chest”;
saddle nose;
change in skull shape:
flat feet;
clubfoot;
pathology of the muscular system - atrophy, divergence of the rectus abdominis muscles.

Diagnostic methods

Connective tissue dysplasia is not only a disease, it is the body’s reaction to the action of unfavorable environmental factors.

CT scans can help identify problems with bones and joints.

Important To diagnose hereditary diseases and dysplasia, it has a method of genealogical analysis - identifying signs of pathology in relatives. A laboratory method allows you to determine the presence and amount of collagen breakdown products in the urine. These indicators are quite informative when diagnosing connective tissue dysplasia. Instrumental methods used to examine organs and systems of the body:

Radiation methods, radiography, computed tomography to identify pathology of the osseous-articular system.
Ultrasound is used to study internal organs and soft tissue diseases.
Endoscopic methods, including bronchoscopy, gastroscopy, cystoscopy, are used to examine the respiratory, digestive, genitourinary systems body.

The clinical picture is complemented by studies by doctors of other medical specialties. The ophthalmologist finds myopia and astigmatism in the child, the pulmonologist finds frequent bronchitis and pneumonia, the urologist finds a “wandering” kidney. The most serious, life-threatening changes that cause sudden death are identified by a cardiologist - mitral valve disease, aortic stenosis, arrhythmia.

Congenital problems are not uncommon nowadays, because a pregnant woman and her child are affected by a huge number of negative factors, from poor ecology, heredity, to stress at work. The combination of all these points cannot provoke a lot of different diseases.

Connective tissue dysplasia is a combination various symptoms that appear during the development of the child. Often this disease is accompanied by problems with the joints, spine and even teeth; the child’s bite changes; flat feet and other unpleasant diseases may also appear.

Connective tissue dysplasia is a disorder of its development that occurs through mutations in genes. Typically, connective tissue is found in all parts of the body and forms the basis of organs, tissues and muscles. It can be loose or dense, and consists of intercellular substance, cells and fibers.

Thanks to the substances collagen and elastin, connective tissue is elastic, strong, and can withstand heavy loads and protect joints from injury. But when the gene responsible for the production of collagen and elastin is mutated, connective tissue is not formed correctly, it loses its elasticity and cannot cope with its job.

Connective tissue allows the entire musculoskeletal system to function normally, and if it is underdeveloped, then under the most ordinary loads the joints and skeleton become deformed, causing pain to the child and making him disabled. It is important to note that the disease does not manifest itself immediately and disorders may not be noticeable for a long time.

Causes

The disease occurs when the synthesis of collagen and elastin, as well as enzymes necessary for connective tissue, is disrupted. In the body of a healthy person, there are 40 genes that are responsible for the production of substances necessary in a particular case, and if any mutation occurs in one of them, for example, a protein replacement, then disorders appear.

The exact cause of such mutations is not known, but doctors note that in cases where the mother’s body was affected by the following negative factors, the risk of disease is higher:

Poor maternal nutrition, vitamin deficiency. In particular, it was noted that the disease may be associated with a lack of magnesium.
Poor ecology often causes various mutations;
Bad habits of the mother before pregnancy, these include smoking, alcohol and especially drug addiction;
Chronic stress;
Complicated pregnancy;
Infections in the mother.

In general, many factors that negatively affect human health can give rise to mutation when conceiving a child. These include even long periods of exposure to the open sun, working in hazardous industries, and much more.

Kinds

Connective tissue dysplasia in children is not a separate disease, it is a collection of various signs and symptoms, and is divided into two types:

Differentiated dysplasia usually rarely appears in children, it is characterized by local damage to one or more organs, and can appear in the joints, skin and spine. This disease is detected immediately, as it is accompanied by obvious symptoms. For example, we can cite a disease such as osteogenesis imperfecta. In this case, the patient suffers from increased fragility of bones, the texture of which is disrupted due to improper collagen synthesis. Also in this case can be attributed a disease called lax skin syndrome, when it lacks collagen. With this disease, the skin sags and the child becomes like an old man.
Undifferentiated connective tissue dysplasia (UCTD) is most common and affects people of all ages. This diagnosis is made if differentiated dysplasia cannot be established. With undifferentiated dysplasia, it is not local areas of the body that are affected, but almost all tissues to one degree or another.

Symptoms

Typically, when visiting a specialist, the patient voices a large number of complaints:

poor appetite and abdominal pain, gastrointestinal problems;
decreased performance, drowsiness and general weakness;
low blood pressure;
frequent lung infections, bronchitis;

Connective tissue dysplasia, as a rule, is not diagnosed immediately. Symptoms occur both individually and all at once, but it is impossible to immediately diagnose them, since they resemble a number of other diseases. During the examination, the doctor pays attention to the following symptoms:

curvature of the spine;
underweight;
curvature of the chest;
changes in body proportions, for example, arms or legs can lengthen symmetrically;
too high plasticity of the joint, when the patient can rotate the limb 90 degrees;
various pathologies of the skin, for example, when it is stretched too much or is easily injured, sagging for no reason;
visual impairment;
fragile vessels, early varicose veins.

Treatment

At the first visit, the doctor usually interviews the patient and his parents, takes an anamnesis, and, taking into account the symptoms seen, sends for tests. Using special molecular genetic methods, specialists can quickly detect pathology if it is present.

Treatment for connective tissue dysplasia involves reducing unpleasant symptoms and improving quality of life. Since the disease is genetic, it is not possible to cure it completely, but it is quite possible to prolong life as much as possible and make it comfortable.

This disease is treated comprehensively, using the right lifestyle and physiotherapeutic procedures, taking special drugs, in some cases surgery may be indicated.

Many people are interested in which doctor treats connective tissue dysplasia; an orthopedist deals with this. But first of all, the child is usually shown to a pediatrician, who, suspecting the presence of signs of an orthopedic disease, should immediately refer the parents to a specialist.

Patients with connective tissue dysplasia syndrome are advised special diet, sports, such as swimming, therapeutic massage courses. Doctors also usually prescribe physiotherapy, physical therapy, UV irradiation, special wraps and baths.

The following drugs are prescribed for treatment:

magnesium, ascorbic acid— these substances are necessary to stimulate collagen production;
Rumalon - this drug helps restore the intercellular substance;
osteogenon - improves metabolism in connective tissue;
glycine - improves mental activity and calms, while normalizing amino acid levels;
lecithin - improves general health child, gives energy.

Special meals are prescribed, with big amount meat, fish, seafood, cheese, nuts. The child must eat enough and often enough to necessary substances entered the body constantly, maintaining normal level collagen, this will help stop further destruction of the body.

Surgery is rarely prescribed for children, only in cases of severe deformation of the spine and chest or blood vessels, when surgical intervention is simply necessary. In order not to reach this state, you need to show the child to the doctor at the first complaints.

FTA

Mixed connective tissue disease (MCTD) is a rare pathology that usually occurs among young and middle-aged women; the disease rarely affects men. This disease is hereditary and autoimmune, it occurs in people with the HLA B27 antigen.

Just like dysplasia, mixed disease has a large number of symptoms that can be substituted for other diseases, which greatly complicates diagnosis. Here are a few of them:

cold hands, pale fingertips;
polyarthritis, disorders motor activity joints;
skin rashes;
baldness;
thirst and dry mouth;
swollen lymph nodes, fever;
redness of the eyes, etc.

Treatment for this disease is aimed at reducing symptoms in order to improve the quality of life, mainly using anti-inflammatory and painkillers and other drugs as needed, for example, cytostatics. If the patient consults a doctor on time, the prognosis for him is usually quite favorable. If the disease is not treated, there is a risk of death due to infections that affect a weakened body.

Prognosis and complications

Connective tissue dysplasia is incurable genetic disease, but with the right and timely treatment the prognosis may be quite favorable. Usually, if the patient eats well, he will healthy image life, takes medications according to the schedule and fulfills all other doctor’s instructions, then the quality of his life improves significantly and the disease does not bother him for many years.

It is important to note that dysplasia affects other diseases the patient may have and usually makes the condition worse. Therefore, different people may have completely different prognosis, which can only be accurately stated by the attending physician based on tests.

To reduce the risk of complications, it is necessary to abandon heavy sports, work with vibrations in the future, you should not be nervous and perform stretching exercises for the spine and joints. Also, patients with dysplasia are not recommended to live in countries with hot climates.

Prevention

Prevention of connective tissue dysplasia consists primarily of maintaining a healthy lifestyle for the mother. Before pregnancy, you need to lead a healthy lifestyle, you need to stop taking drugs, abuse alcohol and tobacco. It is also recommended to get tested for infections. A pregnant woman should eat right, try to take care of herself, and avoid injuries and stress.

The concept of DST unites a number of syndromes caused by abnormalities in the structure of connective tissues. These types of tissues include blood, lymph, they are part of fatty tissue, bones, cartilage and mucous membranes, and form the collagen framework of the skin. Currently, more than a dozen diseases are known, the development of which is provoked by connective tissue dysplasia.

Development mechanism

Connective tissue is built from cellular structures of various types and extracellular substance, which contains collagen fibers, polysaccharides, proteins minerals. If tissue cells are formed “with errors,” it is not able to fully cope with its functions, which sooner or later leads to the development of a certain pathology.

Incorrect formation of connective tissue in most cases occurs during the embryonic development of a child or after his birth and is caused by genetic abnormalities. The tendency to DST is inherited. According to the results of medical examinations of Russian schoolchildren, manifestations of the disease, to one degree or another, are found in almost half of the children.

Signs

Most often, dysplasia is manifested by pathologies of the musculoskeletal system:

joint hypermobility;
anomalies of skeletal structure;
prone to fractures and dislocations;
muscle weakness.

The appearance of patients with connective tissue dysplasia is typical: they are tall, narrow-shouldered, thin, with a very flexible body and elastic skin.

People with DST syndrome often develop valvular heart defects and diseases associated with vascular fragility (reticular varicose veins, rosacea). Manifestations of the syndrome may be low performance, fatigue, intolerance to large physical activity. Often the development of the disease is accompanied by such neurological manifestations, such as autonomic dysfunction, increased emotionality and a tendency to depression.

Types of connective tissue dysplasia

There are two types of DST. The first one, differentiated dysplasia, is quite well studied, since its manifestations are typical, and genetic defects limited. This group of diseases includes the so-called collagenopathies, caused by the gene factor responsible for the formation of collagen.

Diagnosis undifferentiated dysplasia is given if the genetic disorder cannot be accurately determined. Such people have a tendency to develop a variety of pathologies, and although they are not considered sick, they should be under constant medical supervision.

Diagnostics

The presence of signs characteristic of dysplasia is detected during laboratory and instrumental studies.

Standard laboratory methods diagnostics are used:

blood chemistry;
determination of hemostasis indicators;
study of immunological status;
Skin biopsy to determine collagen status.

Hardware diagnostic methods for DST include:

Ultrasound of the abdominal organs and kidneys;
fibrogastroduodenoscopy;
X-ray of the lungs;
Cardiography and echocardiography;
X-ray of joints and spine.

One of the most reliable screening diagnostic methods is a visual examination of the papillary pattern of the skin: when hereditary disorders connective tissue, its relief differs from the typical one (the so-called unformed type of structure).

Which doctors treat STD?

There is no treatment for connective tissue dysplasia as a separate disease. On initial stage Patients with DST are treated by a pediatrician or therapist. But since cellular structures Connective tissue is present in almost any organ; patients with signs of dysplasia are seen by different specialists, depending on how DST manifests itself and what pathology it caused.

The treatment of diseases of the musculoskeletal system (kyphosis, scoliosis, lordosis, chest deformation, flat feet) is carried out by an orthopedist, osteopath, and specialists in kinesitherapy and exercise therapy.
In case of development of cardiovascular pathologies, the patient is managed by a cardiologist.
If, as a result of connective tissue dysplasia, the functioning of the digestive system is disrupted, the patient will be observed by a gastroenterologist.
If kidney and urinary system diseases occur as a result of DST, they are treated by a nephrologist or urologist.
Disorders of the central nervous system caused by connective tissue dysplasia are treated by a neurologist; in some cases, the help of a psychotherapist, a specialist in acupuncture or balneotherapy is required.

Patients diagnosed with DST are recommended to lead a gentle lifestyle: avoid physical and mental stress, adhere to the principles of a healthy diet and daily routine. The diet should include foods rich in proteins, vitamins, microelements, and containing collagen and elastin.