A test developed in Slovakia
Chromosomal disorders
The story of DNA
Human hereditary information is coded in the chemical language of deoxyribonucleic acid (DNA). DNA is stored in the structures of the cell nucleus, in the chromosomes. Any nucleus of a healthy human cell contains 46 chromosomes arranged in pairs (23 chromosomes coming from the father and 23 originating from the mother). To facilitate identification, individual chromosomal pairs are designated by numbers from 1 to 22. The last pair of chromosomes is made up of sex chromosomes. They are labelled as X and Y. If a XX pair is present, the individual is female, in the case of a male we find an XY pair.
In every single healthy cell, there are 46 chromosomes arranged in pairs. Sometimes, however, there occurs a random error of division and instead of a pair of chromosomes, there is a triplet present in the cell – in such a case we talk of trisomy or a chromosome may be missing in the pair, and then we are looking in a case of monosomy. Any change in the number of chromosomes may have a serious impact on the further development of the fetus. Similarly, a random error may result in the loss (deletion) or multiplication (duplication) of a specific part of the chromosome, causing subchromosomal aberration.
Trisomy – random division error
Trisomy is not a genetic disorder with family history inherited from ancestors. It is almost always a new error that occurs in the early stages of embryonic development. The risk of trisomy increases with the age of the future mother. The best-known trisomy is trisomy 21, causing the so-called Down syndrome Trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) are significantly less frequent. Sex chromosome (X and Y) number disorders are common, too. The risk of this particular disorder is investigated by trisomy test XY.
Approximate age risk for women concerning the childbirth for a child with Down syndrome
1 in 1,000
women aged30
1 in 100
women aged40
1 in 10
women aged50
Which chromosomal
disorders do we test?
Chromosomal disorders can cause a large number of diseases with a serious clinical picture and poor prognosis. Our tests investigate the most frequently found chromosomal disorders.
Down syndrome – trisomy 21
The cause of Down syndrome is trisomy 21 – a disease caused by the redundant chromosome 21. Only two-thirds of pregnancies with detected Down syndrome end in normal delivery. Approximately 30% of these pregnancies result in spontaneous miscarriage. The disease has a serious impact on overall growth and thriving of the child, as well as the formation of the body proportions. It is associated with a characteristic facial expression and a disorder of mental and psychological functions of varying degrees. Immune, circulatory or gastrointestinal disorders represent another common complication. Children with trisomy 21 require special medical care depending on the extent of the disability. However, in some cases, Down syndrome can be milder and allows the patient to live a long life.
Edwards syndrome (trisomy 18)
Edwards syndrome develops as a result of trisomy of chromosome 18. The consequences of this chromosomal disorder are severe – the baby is born with a low birth weight, has an abnormally shaped head, small jaw, small mouth, and suffers from frequent cleft lips and palate. The newborn has difficulty breathing, eating, and cardiac disorders may also be associated. The prognosis is very unfavorable. Pregnancies associated with Edwards syndrome are accompanied by a high rate of abortion and most live newborns do not survive for more than 1 year.
Patau syndrome – trisomy 13
If there occurs trisomy of chromosome 13, we are looking at a case of Patau syndrome. Trisomy 13 is a severe genetic disease that can affect all organs in the body, including the brain, heart and kidneys. Babies may be born with a cleft palate and deformed limbs. Newborns with this birth defect have very little chance of survival. Pregnancies with Patau syndrome are characterized by a high risk of spontaneous miscarriage or stillbirth.
TURNER SYNDROME – 45, X
One sex chromosome is missing from the chromosome set and the gonosome complement contains only a single X chromosome. The incidence of Turner syndrome is 1 : 2500 newborn girls. The decisive symptoms of a well-developed clinical picture of untreated cases are low height (already at birth or at an early age), incomplete development of secondary sexual characteristics including amenorrhea and infertility. Impaired growth and development of sexual characteristics is partially treatable by hormonal substitution and has become increasingly successful in recent years. Infertility treatment is enabled by applying the more developed assisted reproduction techniques.
A number of other symptoms will disappear over time, with treatment (e.g. lymphoedema) or will improve (e.g. pterygium colli and shield chest). However, the clinical picture of Turner syndrome also includes congenital kidney defects and developmental heart defects.
KLINEFELTER SYNDROME – 47, XXY
In the chromosome set with an otherwise male XY gonosome complement, there is (at least) one extra X chromosome. The incidence of Klinefelter’s syndrome is 1 : 500 of newborn boys. The decisive symptoms of a well-developed clinical picture of untreated cases of Kleinfelter syndrome include higher growth associated with incomplete female secondary sexual characteristics (gynecomastia, gynoid obesity), incomplete puberty and infertility. These boys tend to be more quiet and more sensitive, they have speech developmental disorders as well as learning disorders. In the genital area, small and/or undescended testes and a smaller penis are typical, hypospadia is found more often, too. Compared to other men, these individuals have an elevated risk of developing diseases affected by XX gonosomal complement, such as breast cancer. Testosterone deficiency, incomplete puberty and the development of sexual characteristics are partially treatable by hormonal substitution. Infertility treatment is enabled by applying the more developed assisted reproduction techniques.
Most of the relevant guidelines do not recommend informing the pregnant woman about the suspected Turner syndrome, or Klinefelter syndrome and it is not recommended to indicate verification by invasive means (e.g. amniocentesis). In accordance with these recommendations, in the result of the TRISOMY test, we inform the pregnant woman about the predicted fetal sex and do not mention any secondary findings concerning an altered number of gonosomes. Before carrying out TRISOMY + test, the pregnant woman should decide whether she wants to know the physiological chromosomal sex of the fetus, and if so, whether she wants to be informed about any possible findings of syndromes 45,X or possibly 47,XXY findings responsible for Turner and Klinefelter syndromes. Compared to autosomal aberrations (especially chromosomal trisomies 21, 18 and 13), the number of requests for termination of pregnancy decreases when gonosomal aberrations (45,X and 47,XXY) are found within the scope of prenatal genetic diagnostic procedures. Therefore, we respect the recommendations that suggest informing the future mother about the suspicion and/or completion of differential diagnosis under postnatal conditions and offer this service in line with the decision made by the pregnant woman and according to the opinion of the indicating physician.
XYY and XXX Syndromes
This syndrome occurs with an incidence of 1 : 1000 newborn boys. The clinical picture is rather inconspicuous. Men with XYY syndrome have above-average height and physiological sexual development. In childhood, XYY syndrome is associated with mild disorders (disorders of speech development, learning, motor skills, emotions, as well as symptoms from the so-called autistic spectrum).
This syndrome occurs with an incidence of 1 : 1000 of newborn girls. The clinical picture is rather inconspicuous. Women with XXX syndrome have above-average height and physiological sexual development. In childhood, XXX syndrome is associated with mild disorders (disorders of speech development, learning, motor skills, emotions and congenital kidney defects are more frequent, too).
Most relevant guidelines do not recommend informing the pregnant woman of the finding concerning the XYY or XXX syndrome and it is not recommended to indicate verification using a sample obtained by an invasive method (e.g. amniocentesis). In accordance with these recommendations, in the result of TRISOMY test, we inform the pregnant woman about the predicted fetal sex and do not mention any secondary findings concerning an altered number of gonosomes. Before carrying out TRISOMY + test, the pregnant woman should decide whether, incompliance with all generally indication criteria, she wants to know the physiological chromosomal sex of the fetus, and if so, whether she wants to be informed about any possible findings of XYY and XXX syndromes or she wants to be informed only about the 45,X or possibly 47,XXY findings responsible for Turner and Klinefelter syndrome (with the limitations stated above).
MICRODELETION SYNDROMES
Due to biological and technical limitations, the accuracy of the test screening for microdeletion syndromes is lower compared to trisomy 21, 18, 13. Because of the low incidence of microdeletions in the population, validation studies are not available to reliably verify the accuracy of the test for these syndromes.
Syndrome name
DiGeorge Syndrome
1p36 deletion syndrome
Prader-Willi and Angelman syndrome
Cri-du-chat syndrome
Wolf-Hirschhorn syndrome
DiGeorge syndrome 22q11.2
It’s the most common microdeletion syndrome. It causes a severe disease, in some cases only partially symptomatically treatable, which can be manifested in any human system and in any part of the body. The main characteristics are congenital heart defects, immune disorders, renal and cleft defects, and often severe mental retardation. The manifestations of the disease are very variable and in some cases (with less pronounced symptoms), familial transmission and intrafamilial variability can also be assumed.
It is also one of the most common microdeletion syndromes. The result of the 1p36 deletion is a very severe and incurable disease with a markedly heterogeneous symptomatology. The main characteristics include mental retardation with behavioral disorders, growth retardation and hypotonia.
PRADER-WILLI SYNDROME and ANGELMAN SYNDROME 15q11
“At the chromosomal level, both syndromes with different clinical picture are caused by loss or impairment of gene function in the same segment of the critical region of chromosome 15. Therefore, the microdeletion test cannot be expected to capture all real cases of these two syndromes.
Prader-Willi syndrome is characterized by hypotonia, weak suction reflex and failure to thrive from birth. After the second year of life, conversely, the child suffers from hyperphagia and obesity. Mental retardation is milder, but in addition to profligacy, the child also shows various behavioral disorders.
Angelman’s syndrome has milder symptoms, the clinical picture is usually not apparent at birth and develops around the first year of age. It manifests itself as a lag in psychomotor development and speech development. Moderate mental retardation is gradually increasingly accompanied by significant behavioral disorders.”
Cri-du-chat syndrome (5p15)
The name Cri-du-chat (“cry of the cat” in French) refers to the key clinical symptom of this syndrome in the newborn age, which, together with characteristic facial dysmorphia, distinguishes it from other diseases associated with delayed growth, psychomotor retardation, microcephaly and hypotonia. The extent of the deletion correlates with the severity of the disability.
WOLF-HIRSCHHORN SYNDROME 4p16.3
Also the children suffering from this syndrome have a characteristic facial appearance with microcephaly, hypertelorism, protruding eyes and a short filter. Growth and psychomotor retardation is severe and accompanied by other severe symptoms such as hypotonia, epileptic seizures and congenital and developmental malformations of internal organs (heart, kidneys).
Test overview