From Big Medical Encyclopedia

CHROMOSOMAL DISEASES (Greek chroma color, coloring + soma a body)

— group of diseases, to-rykh are the cornerstone of development the disturbances of number or structure of chromosomes arising in gametes (mature sex cells) of parents or on early reduction stages of a zygote (oospore).

History of studying of X. originates about a wedge, the researches conducted long before the description of chromosomes of the person (see Chromosomes) and discoveries of chromosomal anomalies. Nek-ry X. (e.g., a Down syndrome) were described by clinical physicians as independent nozol. forms even before disclosure of their chromosomal nature.

Since 1959 when fr. researchers Ge. Le Jeune, Gaultier (M. of Gauthier) and R. Turpin for the first time described disturbance of a karyotype at a Down syndrome (see Down a disease, the Karyotype), bystry development of clinical cytogenetics of the person began. The etiology of syndromes of Shereshevsky — Turner (see Turner a syndrome), Klaynfelter (see Klaynfelter a syndrome), Patau's syndromes (see Pa-tau a syndrome) and Edwards was soon opened (see Edwards a syndrome).

With development of methods of an autoradiography (see) identification of nek-ry individual chromosomes became possible that promoted opening of group X., the chromosomes connected with restructurings — syndromes of deletion (see) short shoulders of the 4th and 5th chromosomes, syndrome of deletion of the 13th chromosome, etc. Within several years more than ten X were open., features of manifestations of each of them at the clinical, cytologic, biochemical levels are detailed, their frequency is determined.

Snowballing of the doctrine about X. 20 century after development of methods of differential coloring of chromosomes began in the 70th that allowed to identify precisely individual chromosomes of the person and even their sites. It provided bystry accumulation of kliniko-cytogenetic material and exarticulation of new forms X. In a crust, time the iniko-cytogenetic characteristic about hundred X is known to l. and syndromes.

Classification of X. it is based on types of mutations (see the Mutation) the chromosomes involved in them. Mutations in sex cells lead to development of full forms X., at to-rykh all cells of an organism have the same chromosomal anomaly. The mutations which arose in an embryogenesis (especially on initial reduction stages of a zygote), cause emergence of mosaic forms, at to-rykh only a part of cells has chromosomal anomaly (see Mosaicism).

All main forms and types of chromosomal anomalies are found in the person. In a crust, time 2 options of disturbances of number of chromosomal complements (see Chromosomal complement) — a tetraploidiya and a triploidy as in the form of full forms, and mosaic are described. Other group of syndromes is caused by disturbances of number of separate chromosomes — trisomies (when there is an accessory chromosome in diploid set) or monosomies (one of chromosomes is absent). Monosomies of autosomes (any chromosomes, except X-and Y-chromosomes) are incompatible with life. Trisomies — more often found pathology at the person. So, X are observed., caused by a trisomy of autosomes: on the 13th couple of chromosomes — Patau's syndrome, on the 18th couple — Edwards's syndrome, on the 21st couple — a Down syndrome; much less often X meet., caused by trisomies of the 8,9, 10,14,16,22 couples of chromosomes. Row X. it is connected with disturbance of number of gonosomes. So, the monosomy of X-chromosome (a genotype of HO) is the cornerstone of Shereshevsky's syndrome — Turner, the trisomy of gonosomes (a genotype of XXY) is the reason of development of a syndrome of Klaynfelter.

The most numerous group X. — these are the syndromes caused by restructurings of chromosomes. More than 700 types of these disturbances are described. However not all of them can be considered as an independent wedge, syndromes since at single observations it is impossible to connect a wedge, a picture directly with chromosomal anomaly as etiol. factor. Nevertheless only on autosomes it is possible to allocate apprx. 80 syndromes caused by the reorganizations which are followed by either loss (deletion) of a part of chromosomal material, or its surplus. In this regard allocate chromosomal syndromes of so-called partial monosomies and syndromes of partial trisomies (reduction or increase in number of separate chromosomes not for the whole chromosome, and for its part).

Because an overwhelming part of chromosomal anomalies belongs to the category of lethal mutations, for the characteristic of their quantitative parameters two indicators — the frequency of distribution and frequency of emergence are used.

The actual material of the cytogenetic examination of newborns conducted in several countries (the USSR, Denmark, Scotland, Canada, the USA), gives rather complete and exact idea of the general frequency of X. in human populations, the edge is reached by 1%. At the same time the frequency of separate types makes: anomalies in system of gonosomes among boys — 0,3% (from them XXY — 0,15%, XYY — 0,11%, restructurings X a Y-chromosome — 0,04%); among girls — 0,22% (HO a full form — 0,01%, HO a mosaic form — 0,07%, XXX — 0,14%); trisomies of autosomes — 0,14% (from them a trisomy of 13 — 0,007%, a trisomy of 18 — 0,013%, a trisomy of 21 — 0,12%); restructurings of autosomes — 0,24% (robertsonovsky translocations — 0,1%; reciprocal translocations — 0,09%; inversions — 0,02%; duplications — 0,03%).

It is found out that apprx. 170 of 1000 embryos and fruits perish till the birth (are exposed to so-called pre-natal selection that is clinically expressed by spontaneous abortion or a still birth), from them apprx. 40% — owing to influence of chromosomal disturbances. Nevertheless a considerable part of mutants (carriers of chromosomal anomaly) passes action of pre-natal selection. On average at 7 of 1000 live-born children various chromosomal anomalies are defined. Owing to weight morfol., fi-ziol. and biochemical disturbances most of patients with a syndrome of the Stalemate at and Edwards perishes at early age, with a Down syndrome — before achievement of pubertal age. Patients with anomalies of gonosomes because of disturbances of sexual development and quite often expressed endocrinopathies, as a rule, do not leave posterity. Therefore, all anomalies of a karyotype (chromosome number) are again arisen and they can be carried to mutations, we eliminiruyushchitsya in firstgeneration, i.e. they exist in population with that frequency, about a cut arise. At different stages of ontogenesis also anomalies of structure of chromosomes are affected by natural selection. It is shown that generally chromosome mutations almost completely disappear from population through 15 — 17 generations after the emergence.

For all forms X. the general sign is plurality morfol., fiziol. and biochemical disturbances. The main the wedge, manifestations are characterized by disturbances of a morphogenesis in the form of multiple inborn malformations. Their formation begins with a stage of a histogenesis and continues in an organogenesis that probably and explains similarity a wedge, pictures at different forms X. General manifestations different X. are: a delay of physical and psychomotor development, mental retardation of various degree of manifestation, craniofacial a dysplasia, kostnomyshechny anomalies, defects cardiovascular, urinogenital, nervous and other systems, a deviation in the hormonal, biochemical and immunological status.

Extent of defeat of bodies and systems at X. depends on many factors — like chromosomal anomaly, identity on gene structure of the chromosome involved in anomaly, the size of missing or excess material of an individual chromosome, degree of mosaicity of an organism (see Mosaicism) on an abnormal cellular clone (see), a genotype of an organism, conditions of the environment, in to-rykh the organism develops.

Diagnosis of X. it is based on kliniko-morfol. and cytogenetic methods. The disturbances of a morphogenesis which are clinically defined as inborn malformations are characteristic feature almost all X. At separate forms about 20 congenital anomalies and malformations of various bodies and systems come to light. One signs are rather constant for all or the majority of chromosomal anomalies, others — meet only at certain X., the third — only at this X. Diagnosis on a wedge, a picture is not really reliable and always demands cytogenetic confirmation.

Depending on research objectives apply cytogenetic express methods — the analysis X-and Y-chromatin (see. Sex chromatin) and methods of the exact chromosomal analysis with special differential coloring of chromosomes (see Chromosomes). The choice of this or that method of the analysis of chromosomes depends on a research objective and a required accuracy rate. In case of unusual a wedge, pictures of syndromes with numerical anomalies of chromosomes or at suspicion on existence of restructuring it is necessary to investigate chromosomal complements, using several methods of differential coloring of chromosomes. In some cases specification of existence of microreorganization or option of a chromosome requires use of highly allowing methods of the analysis of prometaphase or pro-phase chromosomes.

Etiological treatment of X. in a crust, time it is not developed. Pathogenetic methods of treatment include correction of metabolic and hormonal disturbances.

The symptomatic treatment is applied practically at all forms X. also includes physical therapy, purpose of vitamins and others to lay down. actions. It is necessary to exclude at the same time the factors strengthening manifestations of X., and also to apply special methods of education and training that allows to provide sufficient social adaptation in many cases.

The forecast at X. depends on weight of defeat of bodies and systems, adequacy of the held medical events. Basis of prevention of X. medicogenetic consultation is, a cut concludes-etsya in definition of the forecast of the birth of the child with chromosomal pathology (see. Medicogenetic consultation). Development of methods of prenatal diagnosis does this approach by one of the most effective in fight not only with chromosomal, but also with other hereditary diseases (see).

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H. P. Kuleshov.