modern representations about a syndrome of a dysplasia of a connecting tissue

The dysplasia of a connecting tissue (DST) is a group of genetically heterogeneous and clinically polymorphic pathological conditions united by disturbance of formation of a connecting tissue in embryonal and postnatalnom the periods [91].

For the first time the given syndrome was it is described in 1682 by the surgeon from Amsterdam J.Van Meekeren, then Williams (1876), and also Russian researcher A.N.Chernogubovym (1891) and Marfanom (1896). Further have described DST Ehlers (1901) and Danlos (1908) [91, 92, 126, 189, 238, 273, 288, 314, 339]. DST it is characterised by prevalence in population, progredientnostju currents, poliorgannostju lesions, clinical polymorphism. These features are caused by variety of functions, ubiquitous diffusion in an organism of a connecting tissue and lead to homeostasis disorder on fabric, organnom and organizmennom levels [26, 66, 89, 90, 92, 149, 189, 190, 225, 239, 316, 274].

The connecting tissue (ST) makes about 50 % of all mass of a body and carries out diverse and vital functions, providing structure of organs and tissues, a constancy of fabric permeability, vodnoyosolevogo equilibriums, immunologic protection [20, 26, 91, 125, 189, 193, 197]. Actually ST consists of cellular elements, fibrous structures and the basic (interstitial) substance.

Fibroblasts are basic specific cells ST, in them synthesis and secretion of collagenic, elastic and reticular fibers, glikoproteinov, proteoglikanov and enzymes is carried out. Except fibroblasts the corpulent take part in biosynthesis of macromolecules ST
Cells. Macrophages and plasmocytes take a leading place in maintenance of protective function ST in an organism. Reticular cells carry out synthesis of reticular and thin collagenic fibers.

Fibrous structures ST are presented by the collagenic, elastic and reticular fibers consisting of collagen and elastin. On a collagen share as a whole it is necessary about 30 % of all fibers of an organism. Features of a metabolism and collagen function make essential impact on formation and development of organs and systems of the person. The space between fibers is filled by complexes of polysaccharides - glikozaminoglikanami and their bonds with fibers - proteoglikanami and glycoproteids [14, 17, 125, 128, 131, 189, 193, 197, 248, 325, 336].

Now 19 types of the collagenic fibers including more than 30 polypeptide alpha chains which genes are located on 12 chromosomes are identified. Each alpha chain contains on the average about 1000 amino-acid rests. The difficult structure of collagen is defined by alternating of molecules of a proline, glitsina, a lysine, and also their hydroxylic forms inherent to collagen - an oxylysine and an oxyproline. Collagenic fibers section into 2 classes. To the first class carry intersticial collagens (I, II, III, V types), components of 95 % of collagenic fibers. The second class is presented by not fibrillar (minor) collagens (IV, VI-XIX types) [17, 264].

At the heart of DST lay molekuljarno-genetic ontogenetic meyohanizmy which lead to structure and function changes soediniyotelnoj to a tissue. Anomalies desmogeneza are closely bound as to disturbances of synthesis of collagen and a fibrillogenesis, and with disturbance of its biodegradation, fermentopatijami, defect of a fibronectin, elastin, glycoproteids, proteoglikanov, and also deficiency various kofaktorov enzymes (copper, zinc, Acidum ascorbinicum, oxygen, etc.), participating in formation
Cross-section covalent communications for stabilisation of collagenic structures [132, 193, 246, 248, 252, 256, 267, 281, 289, 300, 307, 326, 332].

In clinic DST development mutations of the genes coding synthesis and the spatial organisation of collagen, components of an extracellular matrix responsible for formation, the numerous enzymes which are taking part in intra-and vnekletochyonom maturing of collagen and processes of a fibrillogenesis [90, 247, 264, 275, 304, 340] have leading value. Elongation (insertsija) or a shorting (divisions) of a chain of collagen, various tochkovye the mutations accompanied by replacement even of one amino acid, cause disturbance of formation of cross-section communications in a collagen molecule, reduction of its thermal stability, retardation spiraleobrazovanija, change of posttransmitting updatings and intensifying of intracellular disintegration [87, 236, 238, 239, 268, 306]. Abnormal trimery collagen giperchuvstvitelny not only to temperature lifting, but also change rn, to mechanical loads [268, 295, 300, 301, 302]. In turn, disturbance of biological properties of collagen leads progradientnosti connective tissue disturbances at level of tissues and an organism in whole [87, 226].

There are data about a role of exogenous factors in development of disorganisation of a connecting tissue. B. Steinmann with co-authors [321] has shown, that it is possible to explain a variety of clinical implications DST not only presence of various mutant genes or variabelnoj ekspressivnostju one gene, but also action sredovyh factors. High frequency of a pathology of a connecting tissue can be caused also pathogenic influences adverse ecological obstayonovki, a bad food, the stresses, taking place in an ontogenesis [50, 200, 221, 229, 245, 247, 282, 308, 309, 327, 321].

Allocate differentiated and undifferentiated forms DST [94, 104, 274, 321].

To differentiated (syndromic) DST illnesses mo - nofaktornogo character with the established gene defect and, as a rule, the expressed and accurately outlined clinical semiology concern. A classical example differentiated DST are hereditary kollagenopatii - syndromes Marfana, Elersa-Danlosa and Alporta which occurrence is caused by mutations in the genes supervising synthesis of certain types of collagen. Prevalence of differentiated forms DST in population makes 0,9 % [67, 68, 89, 149, 229, 238, 340]. Differentiated DST are characterised by a serious current and complications, most serious of them are stratification and aortic aneurysm rupture, a decompensation of congenital heart diseases, spontaneous ruptures of internal organs [67, 68, 89, 149, 231, 237, 238].

In clinical practice it is necessary to face numerous undifferentiated forms DST is much more often. Undifferentiated DST are diagnosed when at the patient the set fenotipicheskih signs does not keep within one of the differentiated syndromes [39, 66, 89, 149] In their occurrence play a role as mutations of the big number of genes (hereditary burdeness in 79,68 % of cases), and influence of various factors of an environment (disease of mother in the first trimester of pregnancy, teratogennyj effect of medicines, influence of adverse ecological factors etc.). In a pathogenesis of an undifferentiated dysplasia of a connecting tissue the significant role is played by gene polymorphisms [101].

Prevalence of undifferentiated forms DST in population makes 34,25 % [66, 67, 68, 89, 94, 173]. Undifferentiated DST can sometimes remind one of the known differentiated hereditary diseases (the so-called not classified complexes of defects of development with marfanopodobnym or elersopodobnym
Phenotype), but usually has not expressed clinical implications [40, 104, 106, 150, 165, 289, 308].

Prevalence in populations, a variety of possible complications define an urgency of a problem of timely diagnostics undifferentiated DST. However the diagnosis undifferentiated DST seldom meets in the medical documentation. In many medical specialities the nosological forms representing separate implications of hereditary "delicacy" of a connecting tissue from a certain organ or system are allocated. Similar practice does not focus the practical doctor on purposeful search of the system implications DST which is beyond its speciality or not having a clinical manifestation [20, 106, 133, 135, 207, 274, 289, 305, 324, 337].

Besides extreme polymorphism of semiology, unpopularity of the diagnosis undifferentiated DST is caused also by absence of uniform approaches to laboratory and tool diagnostics. So, possibilities of molekuljarno-genetic methods of diagnostics, so significant syndromes in verification Marfana and Elersa-Danlosa, are limited at undifferentiated DST in connection with genetic heterogeneity undifferentiated DST. Opening of the new genes concerning the given pathology, are perspective from the point of view of understanding of its clinical polymorphism, instead of diagnostics [90, 91, 101, 104, 149, 188, 207, 237, 282, 289, 300, 308].

Relative value at undifferentiated DST has also the genealogical analysis. Despite existence of family cases of clinical variants undifferentiated DST, the certain mode of inheritance is traced far not always, and a clinical variety and an asymptomatic current of many implications of the given pathology does maloyoinformativnym studying of the family anamnesis [135, 165].

The limited possibilities in diagnostics DST biochemical methods of research, in particular definition of an egestion with daily urine of an oxyproline - one of the basic amino acids of collagen possess also. If at differentiated DST it is observed appreciable oksiprolinurija at undifferentiated - oxyproline level can be more low or above norm, that, apparently, it is defined by features of a metabolism of collagen at a concrete variant of a current of disease [90, 135, 224, 232].

Absence of specific molekuljarno-genetic and biochemical markers only underlines a priority of an estimation of clinical implications in diagnostics undifferentiated DST [90, 91, 106, 150, 173, 224].

Clinical implications undifferentiated DST represent a combination of the numerous symptoms reflecting abnormal biosynthesis or degradation of fibrous structures of a connecting tissue which major component is collagen. Wraparound diffusion to an organism of a connecting tissue defines sistemnost, poliorgannost implications undifferentiated DST, the most expressed lesions undergo tissues with the high maintenance of collagen. Qualitative and quantitative changes of structure of collagen are accompanied by secondary metabolic shifts in other structural elements of a connecting tissue: elastic and retikulinovyh fibers, proteoglikanovyh complexes and glikoproteinah [39, 50, 189, 201, 232, 235, 323, 328].

Clinical implications (fenotipicheskie markers) undifferentiated DST can be sectioned on external, taped at the general survey, and visceral. To external fenotipicheskim to markers undifferentiated DST the asthenic somatotype, anthopometrical features (high growth, deficiency of mass of a body concern,
Relative prevalence of length of extremities), various anomalies of a structure of a skeleton, the copular apparatus, eyes, a skin and its appendages [40, 88, 94, 201, 243, 282, 318]. External fenotipicheskim markers posess a special role in timely diagnostics undifferentiated DST. Their revealing allows to suspect presence of accompanying visceral anomalies. The more fenotipicheskih signs it is taped at survey, the it is more than bases to expect pathological changes and in internal organs [13, 221, 234, 283, 328].

The pathology of an organ of sight is the widespread phenomenon at DST [15, 47, 106, 173, 187, 215, 217, 220]. Progressing short-sightedness at children often assotsiirovana with DST, being its significant marker [15, 47, 91, 140, 141, 181, 187, 217, 220]. Prevalence of short-sightedness,

Combined with syndrome DST, at children of school age, according to various authors, is in limits from 39,0 % to 79,2 % [140, 141, 181, 250, 313].

At the heart of short-sightedness the axial component which is in turn bound to basic functions of a sclera lays. Basic function of a sclera is defined by its characteristics: durability, elasticity, a mechanical strain, anisotropism. Change of a thickness also is elastic-prochnostnyh parametres of a sclera which in larger degree are defined by depression by the maintenance in it glikozaminoglikanov, general collagen, depression of level of the cross-section communications stabilising a collagenic fiber, are one of mechanisms of development of short-sightedness [2, 28, 31, 117, 119, 140, 146, 147, 148, 192, 208, 233, 262, 285, 291, 292, 299, 315].

The described anomalies of structure of a collagenic stroma of a sclera often are a consequence DST. In connection with high level of the maintenance of collagen in an eyeball presence of genetically caused defect of collagen leads to polymorphism of clinic of short-sightedness [121, 123, 140, 244, 249, 250, 258, 262, 263, 265, 266, 277, 285, 290, 292, 296, 297].

Retina amotio, miopicheskaja makulopatija, peripheric vitreohorioretinalnye retina dystrophias, a vitreous destruction, augmentation of length of an eyeball at delicacy of a sclera of a back pole, the blue scleras, the enlarged angle of the forward chamber of an eye - the signs defined at undifferentiated DST [26, 66, 90, 91, 97, 98, 149, 188, 265, 291].

Myopia development at DST is accompanied also by influence on akkomodatsionnyj the apparatus. In most cases depression of volume of relative accommodation [140] thus becomes perceptible. However, at children at short-sightedness, assotsiirovannoj with DST, a larger variety of variants akkomodatsionnogo the answer becomes perceptible: delicacy of accommodation, normal akkomodatsionnyj the answer, an is habitual-superfluous strain of a ciliary muscle that reflects the big functionality of a ciliary muscle [19]. Thus the condition akkomodatsionnogo the answer does not depend on size of short-sightedness and the tendency to larger frequency of occurrence normal akkomodatsionnogo the answer at children with short-sightedness, assotsiirovannoj with DST, in comparison with short-sightedness without signs DST [19] becomes perceptible. Therefore it is possible to assume about larger therapeutic effect of conservative methods of treatment at patients with short-sightedness against undifferentiated DST [19].

Expression of the clinical implications of short-sightedness set forth above is enlarged in process of rising of level connective tissue stigmatizatsii [140, 296]. Most often from soedinitelno-woven signs children from myopias have asthenic constitution, an arachnodactyly, anomalies of an occlusion, the small or grown ear lobules of ears, hypermobility of joints and the raised extensibility of a skin. Frequency of occurrence of the above-stated signs accrues in process of rising of size of short-sightedness [140].

At DST the lesion often is not limited to one system. So the combination prolapsa the mitral valve and short-sightedness in 43 - 65,5 % of cases [24, 40, 90, 126, 188, 198, 217], OOZES and short-sightedness in 43,5 % of cases [72, 116] is described. M.I.Kozhanovoj's researches [111] also confirm, that teenagers with short-sightedness suffer diseases of organs of digestion (74,4 %) is more often, further there are illnesses of kidneys and urinary ways (65,0 %), breath organs (61,2 %), a pathology of bones and joints (58,6 %), cardiovascular system (49,1 %) [111]. The interrelation is taped

Myopias with vegetative disturbances (more often in the form of a vegeto-vascular dystonia) [111].

Thus, prevalence in populations, variety of clinical implications and consequences define an urgency of studying undifferentiated DST. Diagnostics of the given pathology complicate extreme polymorphism of semiology, absence of specific biochemical and molekuljarno-genetic criteria. The clinical diagnosis defines set external and visceral fenotipicheskih markers of "delicacy" of a connecting tissue, and the leading part belongs to the clinician.

Questions of role DST in a pathogenesis sochetannoj pathologies remain insufficiently investigated. Short-sightedness often survey as the isolated ophthalmologic pathology without probability of a system pathology of a connecting tissue that reduces efficiency of treatment. In the literature there are no data about research of role DST at the short-sightedness combined with a chronic inflammatory nephrological pathology.

1.2.