Aneuploidy: Symptoms, Diagnosis, Treatment, Types, Stages

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Aneuploidy

The content of the article:

Causes and risk factors
Forms of the disease
Symptoms
Diagnostics
Treatment
Possible complications and consequences
Forecast
Prevention

Aneuploidy is a change in the set of chromosomes, in which their number in cells does not correspond to the norm. Aneuploidy is a collective term: it combines diseases caused by an increase in the number of chromosomes and diseases caused by a decrease in their number.

The normal human genome consists of 46 chromosomes (23 pairs): 22 pairs are represented by autosomes (chromosomes that are the same for male and female organisms), 1 pair are sex-determining chromosomes. So, if a pair of sex chromosomes is represented by a combination of XX, the sex will be female, and if XY is male.

Aneuploidy of autosomes with an insufficient number of chromosomes, as a rule, causes embryonic malformations that are incompatible with life, and is the most common cause of spontaneous abortions (miscarriages) in early pregnancy, during the formation of the internal structure of the future organism.

Viable individuals are capable of developing from a zygote with an increased number of autosomes; at birth, these children are diagnosed with multiple, pronounced developmental anomalies.

Aneuploidy of sex chromosomes usually entails less critical consequences.

Aneuploidy - a change in the set of chromosomes, in which their number in cells does not correspond to the norm

Causes and risk factors

Diseases caused by a quantitative change in the chromosomal set arise as a result of failures during the divergence of chromosomes in mitosis or meiosis. In this case, one or more pairs of chromosomes are not cleaved, and when the cell nucleus is divided, both members of the pair are directed to the same pole, which leads to the formation of a defective germ cell (sperm or egg) with an insufficient or excessive number of chromosomes.

When such a cell merges with a normal gamete carrying a standard chromosome set, a zygote with an odd number of chromosomes is formed: instead of 2, one of the pairs contains 3 or 1. In rare cases, one of the chromosome pairs may be absent or completely duplicated.

According to statistics, the incidence of chromosomal abnormalities in live-born babies is less than 1%, in stillbirths born at term - about 5%, with spontaneous abortion at an early stage - 50–70%. The risk of having a baby with aneuploidy is about 5%, even if both parents are healthy.

Some women are more likely to develop aneuploid embryos, which is associated with a defect in the PLK4 gene. In healthy men, from 1 to 4% of spermatozoa have an aneuploid set of chromosomes.

Risk factors:

the mother's age is over 35 years old (after 45 years, every 5th pregnancy ends with the birth of a child with a chromosomal disease);
history of pathological pregnancies and multiple spontaneous abortions (especially in the early stages);
burdened family history (diagnosed genetic pathology);
the use of prohibited substances;
abuse of tobacco, alcohol;
exposure to toxic agents (acridine dyes, alkylating agents, organic solvents, pesticides, petroleum products, benzene, biopolymers, etc.);
exposure to ionizing radiation;
adverse environmental conditions;
pharmacotherapy with certain drugs (cytostatics, mercury drugs, immunosuppressants, some alkaloids);
transferred viral infections (measles, rubella, flu).

Forms of the disease

Depending on the characteristics of the chromosomes involved, aneuploidy can be:

autosomal;
sexual.

Based on the number of chromosomes involved, the following forms of aneuploidy are distinguished:

nullisomy (absence of 1 pair of chromosomes - 22nd);
monosomy (absence of 1 of paired chromosomes - missing chromosome);
trisomy (a pair of 3 chromosomes instead of 2 is an accessory chromosome);
tetrasomy (a pair consisting of 4 chromosomes instead of 2 - 2 additional chromosomes);
pentasomy (a pair consisting of 5 chromosomes instead of 2 - 3 additional chromosomes).

In the case of a preserved quantitative set, one sometimes speaks of partial monosomy, if significant damage is present in one of the chromosomes with the loss of most of it.

Nullisomy is incompatible with life.

Autosomal monosomy is incompatible with life. Viable children with multiple developmental anomalies are extremely rarely born; they die in the first days of life. Monosomy of the sex Y chromosome is also incompatible with live birth. The most common monosomy of the sex X chromosome is Shereshevsky-Turner syndrome.

Trisomy is the most common form of aneuploidy. The 16th pair of autosomes is most often affected (approximately 1% of all pregnancies), the embryo in this case is not viable, dies during the first trimester of intrauterine development. A child born with a pathology of the 21st pair of chromosomes is viable; this condition is called Down syndrome.

Aneuploidy by sex chromosomes

Other (less common) autosomal trisomies are characterized by multiple developmental defects, including severe oligophrenia; we are talking about the trisomy of the 18th couple, or Edwards syndrome (60% of children die before the age of 3 months, only 5-10% survive to 1 year), and the trisomy of the 13th couple, or Patau syndrome (95% of children die in during the first year of life).

Tetra- and pentasomy are extremely rare, on average with a frequency of 1:18 000-1: 100 000. Pregnancies with these anomalies in the development of the embryo are spontaneously interrupted in the early stages, live birth is almost impossible.

Symptoms

Shereshevsky-Turner syndrome (monosomy of the X chromosome in women), the frequency of occurrence is 1: 5000, manifests itself as follows:

short stature (140-145 cm), lag in physical development;
inharmonious physique;
shortened massive neck;
wide chest with developed muscles;
multiple moles, birthmarks on the background of unchanged skin;
"Gothic sky";
pterygoid folds of skin in the neck;
various bone and articular deformities (hands, elbow and hip joints, spine, tooth growth abnormalities);
anatomical and histological underdevelopment of the genitals and their hypofunction;
arterial hypertension and heart defects (in 30% of cases);
slight drooping of the eyelid, strabismus, the presence of a "third century", visual impairment;
anomalies in the structure of the auricles, minor hearing impairment;
preservation or a slight decrease in intelligence, mental infantilism with euphoric manifestations prevails.

Down syndrome (disease), or trisomy of the 21st pair of chromosomes (on average - 1 case per 700-1000 births), are characterized by:

"Flat" face, sloping back of the head, anomaly of the skull (short-headedness);
skin fold on the back of the neck, massive, short neck;
the presence of the "third century";
decreased muscle tone;
short limbs;
features of the hands (short fingers, curved little fingers, the absence of lines on the palms - one transverse, so-called monkey, fold);
constantly open mouth;
"Gothic sky";
flattened bridge of the nose, short nose;
malformations of internal organs (heart defects, visual organs, gastrointestinal tract, nervous system);
decreased intelligence of varying degrees.

The main signs of Down syndrome

Kleinfelter's syndrome (trisomy of the sex X chromosome in men) occurs relatively often, with an average frequency of 1: 500-1: 700, is diagnosed at the onset of puberty. Cognitive impairments in such patients are absent or mild (according to various sources, 25-50% of cases). The main symptoms are:

high growth (about 180 cm);
disproportionately long limbs;
high waist;
frail, eunuchoid physique with wide hips and narrow shoulders;
sparse hair on the body and face;
female body fat;
abnormally small size of the genitals;
possible bilateral painless breast enlargement;
infertility.

Diagnostics

The main way to diagnose chromosomal aberrations is karyotyping, that is, the study of a set of chromosomes.

In the case of prenatal diagnosis of possible fetal chromosomal abnormalities, several methods are used:

Ultrasound diagnostics;
biochemical examination of the mother's blood for the presence of specific markers (chorionic gonadotropin (hCG), placental protein (PAPP-A), alpha-fetoprotein, free estriol);
non-invasive prenatal DNA test of the mother's blood;
analysis of the karyotype of fetal cells (cytogenetic analysis);
chromosomal microarray analysis (CMA).

Fetal cell karyotyping and CMA are invasive techniques; in other words, they imply instrumental penetration into the cavity of the pregnant uterus in order to collect biological material and are used only in case of an unfavorable genetic history or indirect signs of chromosomal abnormalities obtained using non-invasive techniques.

The study of a set of chromosomes or cardiotyping is the main method for diagnosing aneuploidy

Prenatal diagnosis is carried out twice during pregnancy: the first screening is at 10-14, the second - at 16-20 weeks of pregnancy.

Treatment

Pharmacotherapeutic correction of chromosomal abnormalities at the present stage of development of medicine is impossible.

Patients with chromosomal disorders are recommended:

symptomatic therapy for the treatment of concomitant conditions and complications of the underlying disease;
hormone replacement therapy;
surgical correction of cosmetic imperfections and defects that negatively affect the quality of life.

Possible complications and consequences

Complications of aneuploidies are intensively progressive malformations:

arterial hypertension;
heart defects;
Alzheimer's disease;
episyndrome;
malignant blood diseases;
immunodeficiency states;
acute renal failure;
cataract;
diseases of the thyroid gland;
diabetes;
osteoporosis; and etc.

Forecast

The prognosis for patients with Shereshevsky-Turner syndrome is very favorable in the absence of disabling malformations of systems and organs. Hormone replacement therapy can significantly improve the quality of life.

The prognosis for patients with trisomy 21 (Down's syndrome) is quite good: the average life expectancy with full medical support is 45-50 years. With all-round development and qualified care, children socialize well, master the school curriculum to a limited extent. Cases of people with this pathology receiving university education are described.

The prognosis for patients with Klinefelter syndrome is good.

Prevention

For prevention purposes, the following are used:

medical and genetic counseling for couples at risk (over 35 years old, with a burdened history) at the stage of pregnancy planning;
early prenatal non-invasive diagnosis, which allows you to prevent the birth of a child with serious malformations;
reducing the influence of negative risk factors.

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Olesya Smolnyakova Therapy, clinical pharmacology and pharmacotherapy About the author

Education: higher, 2004 (GOU VPO "Kursk State Medical University"), specialty "General Medicine", qualification "Doctor". 2008-2012 - Postgraduate student of the Department of Clinical Pharmacology, KSMU, Candidate of Medical Sciences (2013, specialty "Pharmacology, Clinical Pharmacology"). 2014-2015 - professional retraining, specialty "Management in education", FSBEI HPE "KSU".

The information is generalized and provided for informational purposes only. At the first sign of illness, see your doctor. Self-medication is hazardous to health!