Chromosomal aberrations are characterized by numerical or structural changes in chromosomes. They are genetic defects that can be visualized by chromosome testing and affect multiple genes. Because of the significant genetic changes, very many chromosomal aberrations are incompatible with life.
What are chromosomal aberrations?
Chromosomal aberrations are genetic changes that affect a wide range of genetic material. Thus, there are numerical and structural changes to chromosomes. Numerical chromosomal aberrations are characterized either by the loss or the excess number of chromosomes. The human genome consists of 23 pairs of chromosomes, with 22 pairs of chromosomes containing autosomes (chromosomes that do not determine sex). The 23rd chromosome pair contains the sex chromosomes X and Y. Here, the X chromosome represents the female sex chromosomes and the Y chromosome represents the male sex chromosomes. In the numerical chromosomal aberrations of autosomes, only some trisomies (3 chromosomes instead of 2) are compatible with life. Monosomies (one chromosome instead of two chromosomes) in autosomes cannot form a viable organism. In the case of sex chromosomes, monosomy with the X chromosome is viable in addition to trisomies. In addition to numerical chromosomal aberrations, there are also structural chromosomal aberrations. These are, for example, deletions, inversions or translocations. Deletions represent shortening of chromosome segments with loss of genetic information. In inversions, broken chromosome parts are reassembled in reverse. Translocations are characterized by relocation of chromosome segments to other locations in the hereditary material. This can also occur across chromosomes.
Causes
There are many causes of chromosomal aberrations. Numerical chromosomal aberrations result from errors during cell division. For example, during meiosis, the two chromosomes of a chromosome set may remain together. Since in meiosis germ cells are formed by bisection of the chromosome set, in the case of faulty division one germ cell (gamete) has a complete pair of chromosomes and the other has no chromosomes at all of the chromosome type in question. If just one of these gametes (egg or sperm) fuses with a normal gamete during fertilization, either a trisomy or a monosomy occurs. With the exception of X monosomy, all monosomies are incompatible with life. However, some trisomies are compatible with life. Numerical chromosomal aberrations can theoretically result in more than three chromosomes in a chromosome set. Structural chromosomal aberrations usually result from breaks in chromosomes caused by exposure to chemical substances, radiation, and other influences. The broken individual pieces are then incorrectly assembled if, in addition, the repair system is malfunctioning. Thus, fragments are lost, whereby the corresponding chromosome is shortened (deletion). Or the fragments are assembled incorrectly (inversion). Fragments or even whole chromosomes can also be attached to other chromosomes. If all hereditary information is preserved in this case, it is a balanced translocation. The affected person is completely healthy. However, his or her offspring may then suffer from a so-called translocation trisomy. They have the normal set of chromosomes and additionally one translocated chromosome. Translocation trisomy produces symptoms similar to those of normal trisomy.
Symptoms, symptoms, and signs
Symptoms in chromosomal aberration depend on the type of disorder. The best known trisomy represents the so-called Down syndrome. In Down syndrome, chromosome 21 is present three times. It is irrelevant whether a normal trisomy or a translocation trisomy is present. Down syndrome is characterized by the characteristic mongoloid eyelid axis position, heart defects or muscle hypotonia. The mental retardation can often be well controlled by intensive support. Life expectancy is 50 to 60 years. Trisomy 13 (Pätau syndrome) and trisomy 18 (Edward syndrome) are also known. Both syndromes lead to death in early childhood.The numerical gonosomal chromosomal aberrations (sex chromosomes), with the exception of X monosomy (Ullrich-Turner syndrome), are often discovered by chance because the symptoms are mild. In Klinefelter syndrome with constellation XXY, eunuchoid tall stature, delayed puberty, infertility and female habitus are noticeable. IQ is usually normal. XXX females and XYY males are usually inconspicuous, so these trisomies are almost always an incidental finding. Among the structural chromosomal aberrations, Cri-du-Cat syndrome (deletion in the short arm of chromosome 5) and Wolf-Hirschhorn syndrome (deletion in the short arm of chromosome 4) are the best known. Both syndromes are associated with severe physical and mental disabilities.
Diagnosis
Chromosomal aberrations are diagnosed by visualizing and evaluating karyograms. To produce a karyogram, cells are stimulated to divide and simultaneously treated with the cytotoxin colchicine to keep the divided chromosomes together. Afterwards, the chromosomes thus determined are viewed under the microscope and photographed. A typical banding pattern presents itself, by which chromosomal changes can be detected quite clearly.
Complications
Chromosomal aberrations can cause various genetic defects and malformations in the patient. In most cases, affected individuals suffer from the so-called Down syndrome. Most syndromes burden the patient with severe malformations. First and foremost, there is a heart defect and also mental retardation. The intelligence of the patient is strongly reduced, although this can be influenced by therapies and other learning methods. Due to the heart defect, life expectancy is reduced to about 60 years. Often the patients also suffer from short stature and other malformations, which can affect the face or the extremities. It is not uncommon for the malformations to cause psychological complaints or depression. The sexual development of the affected persons is also delayed or takes place only in a very limited way due to the chromosomal aberrations. It is not possible to treat chromosomal aberrations causally. The patient has to live his whole life with the symptoms of the respective syndrome. However, many of them can be limited and treated so that everyday life becomes bearable for the patient. Which measures are necessary for treatment and whether there are complications, if any, depend greatly on the genetic defect and the particular measure.
When should you go to the doctor?
In the case of chromosomal aberrations, visits to the doctor depend very much on the severity and nature of the symptoms. Unfortunately, in many cases with chromosomal aberrations, patients cannot survive and die shortly after birth. In this case, a psychologist should also be consulted in case the parents and the relatives suffer from psychological complaints. As a rule, patients with this disease require regular examinations of all organs and bodily functions. Especially the heart must be examined regularly. A visit to the doctor is also necessary if the affected person suffers from mental retardation due to the chromosomal aberrations. In this case, the patient is dependent on special support. As a rule, the diagnosis can be made by a general practitioner or a pediatrician. Further treatment depends on the extent of the complaints and usually takes place at the respective specialists. If the child also suffers from psychological complaints, treatment should also take place with a psychologist.
Treatment and therapy
The therapy of diseases and syndromes caused by chromosomal aberrations is always symptomatic. Causative treatment is out of the question. Some syndromes can be well controlled with concomitant support. This includes Down syndrome. Both mental development and treatment of physical impairments often depend on the support measures initiated and the overall concept of treatment.
Outlook and prognosis
Chromosomal aberrations have a poor prognosis because a cure is not possible. Essentially, however, they are dependent on the disorders present, which manifest individually in each patient. In most patients, chromosomal aberrations are associated with a significant reduction in average life expectancy.Since intervention in human genetics is not legally permitted, no causal therapy and thus no modification of the genetic mutations can take place. Treatment is aimed at alleviating the patient’s existing symptoms. In addition, physicians try to delay the progress of the disease as long as possible with targeted therapies. The chromosomal aberrations are associated with numerous malformations or cognitive impairments. In addition, there are restrictions in development as well as sexual functions. In addition to the physical abnormalities, the chromosomal aberrations can cause numerous psychological disorders. This further decreases the patient’s quality of life and worsens the patient’s overall health. When offspring are conceived, the chromosomal aberrations can be passed on to the next generation. There is a possibility of decreased or increased symptoms there. In syndromes that are well researched, there is a possibility of significant improvement. Support measures as well as an individual treatment concept are used, which represent better development opportunities for the patient.
Prevention
For prophylaxis against diseases caused by chromosomal aberrations in the offspring, intensive human genetic counseling should be performed if cases of the disease have already occurred within the family or relatives. In most cases, these syndromes arise spontaneously. However, there is a certain probability of inheritance in the case of a translocation trisomy. In this case, a clustered familial occurrence is possible, which should be clarified by human genetics.
Follow-up
In most cases of chromosomal aberrations, the affected person has no or only very few aftercare measures at his or her disposal. Since it is a genetic disease, it also cannot be treated completely. Therefore, genetic testing and counseling should always be done when a child is desired to prevent the chromosomal aberrations from occurring in the children. The further treatment depends very much on the exact manifestation of the disease, so that no general prediction can be made. Possibly the life expectancy of the affected person is also reduced. In most cases, the treatment itself is carried out by surgical interventions, which are intended to alleviate the malformations and deformities. After such an operation, the affected person should rest and take care of his body. Efforts and stressful or physical activities should be avoided in any case. Likewise, due to the chromosomal aberrations, most affected persons are also dependent on the help and support of their own family in order to cope with everyday life. In this context, intensive and loving conversations are often also necessary so that psychological upsets or depression do not occur.
This is what you can do yourself
The possibilities of self-help are relatively limited in the case of chromosomal aberrations. The affected person is thereby dependent on a purely symptomatic therapy, since the disease cannot be treated causally. Often, chromosomal aberrations also lead to premature death of the affected person. People suffering from chromosomal aberrations require intensive care and are often unable to cope with everyday life on their own. In this case, care by family or friends is very useful and has a positive effect on the course of the disease. The children also need special schooling, as they suffer from reduced intelligence. However, the exact treatment depends very much on the exact disease, so that here no general prediction can be made. Frequently, contact with other people can also prove to be very helpful, as this can lead to an exchange of information. In the case of psychological complaints or depression, conversations with friends and family can help. However, they are no substitute for a psychologist, so a doctor must be consulted in the case of serious complaints. Also the parents and relatives of the patient often suffer from psychological complaints due to the chromosomal aberrations and are dependent on a visit to a psychologist.