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International Journal of Medical Sciences And Clinical Research
(ISSN
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04
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24-31
OCLC
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ABSTRACT
The article discusses connective tissue dysplasia (CTD) and its genetic basis, classification issues in the International
Classification of Diseases (ICD), research on CTD in Uzbekistan, and the association of CTD with cardiovascular
complications, particularly arrhythmias. Various studies and classifications related to CTD are mentioned, emphasizing
the genetic mutations underlying the disease and the prevalence of arrhythmias in syndromic forms such as Marfan
syndrome and Ehlers-Danlos syndrome. The text underscores the importance of close monitoring, early detection,
and appropriate management of arrhythmias in patients with CTD to optimize outcomes and reduce complications.
Based on the foregoing, the purpose of this work is to establish in posttal ontogenesis the laws of the formation and
involution of bronchial vascular and lymphatic systems in a person, epithelial connective tissue relationships in the air
and respiratory parts of the lung (1.4).
Research Article
FUNCTIONAL COMPONENT OF THE CARDIOVASCULAR SYSTEM IN
INDIVIDUALS WITH CONNECTIVE TISSUE DYSPLASIA
Submission Date:
June 05, 2024,
Accepted Date:
June 10, 2024,
Published Date:
June 15, 2024
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume04Issue06-05
Shodikulova Gulandom Zikriyayevna
Professor, Samarkand State Medical University, Samarkand, Uzbekistan
Gulomov Jahongir Ibrokhimovich
Assistant, Samarkand State Medical University, Samarkand, Uzbekistan
Samatov Dilshod Karimovich
Assistant, Samarkand State Medical University, Samarkand, Uzbekistan
Khasanov Oybek Gafurovich
Professor, Samarkand State Medical University, Samarkand, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
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International Journal of Medical Sciences And Clinical Research
(ISSN
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VOLUME
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ISSUE
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24-31
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1121105677
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KEYWORDS
Connective tissue (CT), Connective tissue dysplasia (CTD), Classification, heart rhythm disorders, functional
component of the cardiovascular system.
INTRODUCTION
Connective tissue is an integral structure, as a result of
which damage to one or another of its components is
accompanied by the development of inevitable
pathological changes in neighboring ones, which
results in a decrease in its functional capabilities [3, 4,
5, 6]. It is assumed that the substrate of the nature of
the alterative component in the pathogenesis of CT
dysplasia is not known for certain, because, as stated
above, to one degree or another, both fibers and the
ground substance of a given tissue are involved, often
to an equal extent [4, 7].
At the current stage of studying CTD, the leading role
of genetics in pathogenesis has been revealed. The
basis for the changes is mutations of genes that store
hereditary information on the processes of synthesis of
the constituent parts of connective tissue, a violation
of which potentiates the disintegration of the
components of the extracellular matrix, which is in the
genesis of the violation of the organ framework and
significantly affects the clinic of associated nosologies
[4, 7, 8, 9, 10, 11, 12].
A study of the genetic load of CTD per population cell,
i.e. a certain family or genus using genealogy,
determining the distinctive properties of the
morphological disorder showed that as we approach
the studied proband and his sibs, dysmorphism is
characterized by the presence of a progressive
increase in persistent and specific signs of CTD, which
can indirectly demonstrate the dominance of
mutations characteristic of this pathology. This
category of patients, receiving the CTD pool of genetic
information from their ancestors, is characterized by a
rapid increase in a specific symptom complex already
in the early extrauterine period of development, which
perturbs in the key periods of childhood and puberty
with the preservation of the desired disorders until the
end of life [7].
Classification issues
The International Classification of Diseases WHO (ICD-
10) does not cover CTD as a separate nosological unit;
on the contrary, there is a need to classify many
pathologies similar to code M35.9 - Systemic lesions of
connective tissue, unspecified, which may in some
situations create inconvenience for their descriptions,
both in the international literature and in the practical
activities of a doctor. Some of the nosologies that
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collectively constitute the vanguard of the connective
tissue dysplasia clinic have separate classification
codes I34.1 - Mitral valve prolapse, H52.1.
–
Myopia,
Q87.4
–
Marfan syndrome, Q79.6
–
Ehlers-Danlos
syndrome, etc.
In ICD-11, despite the introduction of significant
changes compared to the previous version, and as
WHO experts emphasize - more significant clinical
content, DST is not assigned a separate code and it can
refer to LD28.Y - Other specific syndromes with
connective tissue damage as the main symptom or
LD28.Z - Syndromes with connective tissue damage as
the main symptom, unspecified, which once again
indicates the need to conduct research on this problem
from the point of view of different areas of medicine
because the issue of DST is interdisciplinary.
The most common clinical classification of DST is the
division into 2 groups according to differentiation, i.e.
into differentiated and undifferentiated types.
Differentiated dysplasias relative to undifferentiated
ones are quite rare, they are distinguished by the
presence of a clear clinical symptom complex,
represented by gene abnormalities, and are
characterized
by
established
Mendeleevian
inheritance:
Schwarz-Yampel
Meester-Loeys,
Knobloch, Marfan, Ehlers-Danlos, Alport syndromes,
spondyloepimetaphyseal
dysplasia,
osteogenesis
imperfecta, congenital muscular dystrophy Ulrich,
etc.); whereas nonspecific symptoms, widespread
prevalence in the population and an uncertain form of
inheritance characterize undifferentiated forms.
Research in Uzbekistan on this topic
Connective tissue dysplasia and associated diseases of
various organ systems are attracting the attention of
an increasing number of researchers due to the
relatively high prevalence of this group of pathologies.
In our country, scientific research was carried out,
which was fragmentary, until the study by G.Z.
Shodikulova was initiated. Then, under her leadership,
several works were carried out to study connective
tissue dysplasia, the features of the course, diagnosis
and treatment of pathology of the upper
gastrointestinal tract in patients with connective tissue
dysplasia were studied (Samatov D.K., 2023), the
prevalence and features of the course were
characterized undifferentiated connective tissue
dysplasia using the example of Samarkand and Jizzakh
regions (Mirzaev O.V., 2022), the significance of
phenotypic, genetic markers on the development,
course and early diagnosis of undifferentiated
connective
tissue
dysplasia
was
determined
(Babamuradova Z.B., 2020). Despite the significant
progress in understanding CTD, there are several issues
affecting the state of the cardiovascular system in
patients with connective tissue dysplasia, in particular
with heart rhythm disturbances, which require more in-
depth research to prevent cardiac complications and
reduce the burden of their mortality on the population.
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Modern literature is replete with data on a whole
group of monogenic DSTs associated with mutations in
genes responsible for the synthesis of extracellular
matrix proteins (various types of collagens, tenaskin,
fibrillin), genes for growth factor receptors and matrix
metalloproteinases [13].
Data from Lamandé SR, Bateman JF (2020) based on
an analysis of the literature indicate that the set of
genes responsible for the synthesis of vital
components of the extracellular matrix, i.e. The human
matrisome (1,027 genes) is represented by 274 central
genes that make up its “core” and 753 genes
“associated” with it. The most important genes
included in the matrisome core store genetic
information for the biosynthesis of ECM glycoproteins
- 195 genes, proteoglycans - 35 and collagens - 44.
Genes interconnected with this set form groups of
genes responsible for the secretion of factors - 344,
synthesis of regulators - 238, and those closely
associated with the ECM - 171 (the number of genes
studied is indicated after the dash). The authors also
note that of the 195 genes responsible for the genetic
information of ECM glycoproteins, 67 correlate with
genetic diseases or predisposition to them; 27 out of 44
collagen and 11 out of 35 proteoglycan genes are
associated with a number of this type of pathology
[14].
The literature varies on the prevalence of CTD, which
may be due to the genetic heterogeneity of different
populations, the lack of a clear classification and
criteria for stigmatization [7, 15, 16, 17] and a number of
other factors. Methodological approaches and their
heterogeneity in the study of this group of pathologies
deserve special attention:
Martynov A.I. et al. (1998) stated that the presence of
3 signs is sufficient to confirm dysplasia; Klemenov A.B.
(2005)
–
4 for women, 5 for men; N.P. Shabalov, V.A.
Tabolin (1984), E.V. Zemtsovsky (2000)
–
6 signs;
Gorbunova V.N., Kadurina T.I. (2007)
–
from 6 to 8
signs;
The above aspects of research complicate the process
of collecting and collating research results. Also, it is
worth noting a different opinion of a number of
researchers on the diagnosis of DST, testing the
likelihood of an erroneous medical conclusion about
the presence of this disease in the subjects -
overdiagnosis due to the introduction of a quantitative
approach, and therefore, the determination of
qualitative
dysmorphogenesis
and
associated
manifestations may be important [7, 16, 18]. However,
even here, scientists’ views on the degree of quality of
certain characteristics began to differ [7, 19, 20, 21, 22].
The introduction of the latest achievements of
biostatistics into scientific medical use has made it
possible to determine the statistical indicators of
diagnostic measures for the detection of study
participants with and without DST, derived from errors
of the first and second types, i.e. sensitivity and
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specificity, on the basis of which it became possible to
determine the predictive diagnostic value. This
approach made it possible to systematize the
diagnostic significance of individual DST parameters
and, as a result, develop special DST tables aimed at
monitoring the clinic of children and adults [7, 18]. The
practical and clinical significance of the above method
is difficult to deny.
Some studies [7, 17, 19, 21, 23] show wide variation in
the phenotypic burden of CTD, ranging from 1
–
80%. In
Uzbekistan, the incidence of this pathology, according
to the analysis (Shodikulova G.Z., Mirzaev O.V., 2022)
among respondents in Samarkand and Jizzakh regions
was without a significant difference by region, and the
average value of the required indicators in both
regions was about 9%, in particular in Samarkand - 9.9%,
and in Jizzakh - 8.8%, which indicates that almost every
10th resident has a predisposition to CTD or suffers
from it, which, given the age composition of the study
participants, confirms clinical and scientific significance
of the study of this problem.
Connective tissue dysplasia, especially syndromic
forms such as Marfan syndrome, Ehlers-Danlos
syndrome, and Loeys-Dietz syndrome, is associated
with an increased risk of cardiovascular complications,
including arrhythmias. Although exact prevalence data
may vary depending on the specific syndrome and
population
studied,
research
suggests
that
arrhythmias are relatively common in patients with
connective tissue dysplasia.
For example, studies have shown a higher prevalence
of atrial fibrillation/flutter, ventricular arrhythmias, and
conduction abnormalities in patients with Marfan
syndrome [4, 5, 16, 17] compared with the general
population. Similarly, people with Ehlers-Danlos
syndrome [8, 9, 10] may experience a variety of
arrhythmias, especially those associated with
structural cardiac abnormalities such as mitral valve
prolapse and aortic root dilatation.
The occurrence of arrhythmias in patients with
connective tissue dysplasia is influenced by many
factors, including the genetic mutation underlying the
disease, the severity of damage to the cardiovascular
system, and the presence of comorbidities such as
hypertension and valvular abnormalities of the heart.
In addition, age, gender, and lifestyle may also
contribute to the development of arrhythmias in these
patients.
Given the increased risk of arrhythmias in patients with
connective tissue dysplasia, close monitoring, early
detection, and appropriate management strategies are
necessary to optimize outcomes and reduce the risk of
complications.
CONCLUSION
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Thus, the morphological and physiological properties
of the cardiovascular system, mediating the
occurrence of rhythm disturbances in CDT, have a
significant impact on the likelihood of developing
cardiac complications and can negatively affect the
quality of life of patients and the prognosis of existing
cardiac pathologies; CTD accelerates pathological
changes that occur in the heart, which requires a
separate approach to early diagnosis.
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