Pediatric Medical Genetics - S.I. Smiian 2003

Chromosomal diseases
Chromosomal diseases

Chromosomal Disorders are caused by alterations in chromosome number or Structure.

Today, chromosomal disorders are much better understood than Gene disorders. Their genesis involves various changes in chromosome number or structure, which are either inherited from a previous generation or acquired by one of the parents during gamete maturation and manifest for the first time. Structural abnormalities of the chromosomal complex typically involve smaller Chromosomes, as aberrations of larger ones are generally incompatible with life. Such aberrants perish in the Cytology/cytology/16.html">Early stages of Embryogenesis. Disorders within the autosome system, particularly quantitative ones, mostly lead to drastic phenotypic deviations and fetal malformations that are incompatible with life. In contrast to autosomes, abnormalities in the number of sex chromosomes do not lead to drastic phenotypic deviations. While the patient's appearance and the condition of the reproductive, endocrine, and other systems are altered, and such patients are frequently infertile, these changes are not life-threatening.

The Classification of chromosomal disorders is based on the type of genomic and chromosomal mutation and the specific chromosomes involved in the pathological process. This approach maintains the pathogenetic principle, which is essential for the nosological subclassification of hereditary pathology: for each disease, it identifies which genetic structure determines the pathology (the chromosome and its segment) and the exact Nature of the genetic disruption (a deficiency or excess of genetic material). Classifying Genetic Disorders based on their clinical picture is of secondary importance, as it is complicated by the significant overlap in developmental anomalies across different Chromosomal aberrations.

Furthermore, in each specific case of a chromosomal disease, it is determined where the mutation occurred: in the parental Gametes or in the zygote; and whether the mutation is de novo or inherited from parents who harbored it in their somatic Cells prior to gamete formation.

Chromosomal Mutations (whether numerical or structural) can occur in both somatic and Germ Cells. They result from numerical or structural alterations of chromosomes and their sets. Numerical changes involve the presence of extra chromosomes or the absence of one. The former is referred to as trisomy for one of the 23 chromosomes, while the latter is termed monosomy. Less frequently, disruptions in the ploidy of the chromosome set can be observed (an increase by a full haploid set). Such genomic mutations are most commonly found in spontaneous abortuses and may be represented by triploidy and tetraploidy.

Among structural alterations, which are numerous, the following are observed: a) translocations — structural rearrangements of two or more chromosomes involving The transfer of fragments from one chromosome to another; b) deletions — the loss of a chromosomal segment; c) inversions — a 180° rotation of a broken chromosomal segment; d) duplications — additional segments of chromosomal material on one of the chromosomes or as an independent chromosomal fragment; e) isochromosomes — chromosomes with two genetically identical arms formed As a result of transverse rather than longitudinal centromere splitting, etc.

Occasionally, an Organism may contain cells with different karyotypes. This combination of karyotypes is generally termed "mosaicism." In humans, mosaic forms are most frequently detected within the sex chromosome system.

Additionally, Chromosomal diseases can be classified according to which chromosome system—sex or autosomal—is involved in the pathological process.

To date, there is no precise universally accepted Classification of Chromosomal Diseases. This is due to many factors, notably that the pathogenetic mechanisms of chromosomal disorders are not yet sufficiently understood. Most chromosomal aberrations continue to be classified as syndromes. Only a few can be strictly termed diseases. This is entirely true for Down and Klinefelter syndromes.

What is the general clinical profile of all chromosomal disorders?

Nearly all chromosomal disorders are accompanied by multiple skeletal defects, psychiatric disorders, Congenital Malformations of external and Internal Organs, growth retardation, Impairment of the nervous, endocrine, and other systems, reduced regenerative capacity, and increased morbidity and mortality.

Diagnostic features of chromosomal anomalies can be divided into 3 groups:

A — a complex of features that raise suspicion of a chromosomal anomaly. These are general signs: physical underdevelopment, various craniofacial dysmorphisms, Clubfoot, and certain internal organ anomalies (of The Heart, Lungs, Kidneys).

B — features that occur primarily in specific chromosomal disorders. Their combination enables the Diagnosis of a chromosomal anomaly in most cases. Specifically, in trisomy 18 (Edwards syndrome), these include dolichocephaly (89.6%), flexed fingers (96.1%), "rocker-bottom" feet (76.2%), and a short, broad great toe (70.6%). In trisomy 13 (Patau syndrome), these include cleft lip and palate (68.7%), flexed fingers (44.4%), strabismus (31.4%), and scalp defects (30.5%).

C — features characteristic only of specific chromosomal anomalies: the cat-like cry in 5p^- syndrome, and alopecia in 18p^- syndrome.

It is estimated that 0.5% of all newborns have chromosomal anomalies. Approximately 1 in 400 boys and 1 in 600 girls have sex chromosome abnormalities, among which Klinefelter and Turner syndromes are the most frequent. Among Autosomal anomalies, Down syndrome is the most common (1:700 to 1:800), while others occur several times less frequently. Chromosomal anomalies are 4 times more common in premature infants than in full-term ones. The prevalence of chromosomal disorders is even higher in abortus material, averaging 40%. Sex chromosome anomalies include Klinefelter syndrome, Turner syndrome, Triple X syndrome, and others.