Prenatal Diagnosis of Congenital and Hereditary Fetal Pathology


Prenatal diagnosis – comprehensive prenatal diagnosis in order to detect pathology at the stage of intrauterine development.

Hereditary diseases are diseases that are based on a gene chromosomal mutation. Congenital diseases are not always of genetic origin.

Today, it is possible to diagnose almost all chromosomal syndromes and about 100 hereditary diseases.

A karyotype is a human chromosome set – a genetic passport – that does not change during life. Normally, a person has 46 chromosomes (23 from each parent). Normal male karyotype -46 XY, normal female karyotype -46 XX. In some cases, the human karyotype may have anomalies, changes in the number of chromosomes or structural changes (translocations, inversions, insertions, etc.). Such anomalies can be identified during cytogenetic studies (analysis of the karyotype).

The following human karyotype abnormalities occur:

Aneuplodia – quantitative changes in chromosomes.

– monosomy 45, X-Turner syndrome or gonadal dysgenesis;

– trisomy, these include Down syndrome trisomy on chromosome 21, Edwards disease –trisomy chromosome 18, Clifelter’s disease

47 xxx and trisomy 18 chromosome patata syndrome

It is known that the risk of having a baby with Down syndrome in pregnant women increases with age. So, if at 20 years in a pregnant woman the risk of having a baby with Down’s disease is 1 in 1670, then in 35 years the risk is 1 in 365, and in 40 years 1 in 110 births, in 45 years 1 in 32 births.

Polyplody, (triplodia, tetraplody), for example, a well-known pathology – a partial gallbladder is nothing more than a triploid on chromosome 69, when one egg is fertilized by 2 spermatozoa. 69, hhu.

But a full bubble skid – when an empty egg is fertilized, the karyotm is represented as 46XX.

Chromosome structure anomalies:

There is also a pathology such as Gonadal mosaicism, for example, in the clinical practice of obstetrician-gynecologists, when we meet women with premature ovarian depletion (when menopause occurs before the age of 40). The reason for this pathology is precisely the mosaicism of chromosomes, which predisposes to malignancy, that is, the development of ovarian cancer.

About 1% of newborns have so-called Mendel disorders. (Mendelian disoders). 70% of them are autosomal dominant. The rest are autosomal recessive, X-linked and multifactorial.

An example of an autosomal dominant type of disease inheritance is polydactyly, polycystic kidneys, achondroplasia. neurofibromatosis, etc. These diseases are transmitted in all generations, both sexes i. boys and girls.

Examples of autosomal recessive hereditary diseases are: deafness, albinism, sickle cell anemia, thalassemia, phenylketonuria, congenital adrenal hyperplasia, cystic fibrosis, Tay-Sachs syndrome.

For example, Tay-Sachs disease, cystic fibrosis, spinal muscular atrophy are most common in Ashkenazi Jews. Because after the famous historical events between the few remaining Jews of this ethnic group there were many related marriages.

X linked hereditary diseases, which are also inherited by the atuosome-dominant and autosomal recessive types:

Dyushen muscular dystrophy, night blindness, hemophilia A, diabetes insipidus.

Multifactorial congenital pathology means that the development of this defect was affected by several factors, starting with infectious agents, environmental factors, teratogenic drugs, etc.

The multifactorial congenital abnormalities of the fetus include: defects in the development of the fetal neural tube (spinal hernia – spina bifida, anencephaly), congenital heart defects, cleft lip and cleft palate, pyloric stenosis.

The neural tube of the fetus is the bud of the central nervous system and is fully formed by the 28th day of gestation. If there is a shortage in the body of a pregnant folic acid, a defect of its development may occur, it does not close completely, and spinal hernias are formed. Therefore, it is important to saturate the body of a pregnant with folic acid before conception and during the first trimester of pregnancy. At the same time, if the mother has a child with such congenital abnormalities, the risk of re-birth of the child with this abnormality increases by 2-5%.

Ultrasound diagnosis (ultrasound), operative (chorionic biopsy, amnio-cordocentesis, muscle and skin biopsy of the fetus), and laboratory research methods (cytogenetic, biochemical, molecular-genetic) are used.

Currently, prenatal diagnosis is carried out in the I and II trimesters of pregnancy. Non-invasive methods (screening) studies

Further, at 11-13 screening for hereditary and congenital abnormalities of the fetus is carried out, which includes as an assessment of the thickness of the collar area of the fetus during ultrasound (Nuchal translucency) and biochemical markers: PAPP-A and β-HCG free.

At 15-16 weeks of gestation, the second trimester is screened for hereditary and congenital fetal abnormalities based on biochemical markers (β-HCG free + AFP + Estriol free);

At 21-24 weeks the pregnant woman is sent to the radiology department to conduct an extended ultrasound examination in order to exclude hereditary and congenital abnormalities of the fetus.

Indications for invasive procedures are:

  • Age of mother over 35;
  • multiple pregnancy losses, including nondeveloping, spontaneous miscarriages in the first trimester of pregnancy, and stillbirth in history.
  • genetic diseases in close relatives, mental retardation, the birth of children with malformations.

And of course, the inconsistency with the normal indicators of biochemical and ultrasonic markers of non-invasive research methods.

Invasive (operative) research methods are applied only after detecting any inconsistencies with the norm of non-invasive research methods performed.

They  include:

Chorionic biopsy – taking chorionic villi under ultrasound control for further research in order to diagnose congenital and hereditary diseases of the fetus.

Depending on the access chosen, transabdominal and transcervical methods are distinguished. Material is being sampled with 1 and 2 needles.

A chorionic biopsy is performed at 10–12 weeks of gestation.

Amniocentesis – puncture of the fetal bladder in order to obtain amniotic fluid and desquamated fetal amnion cells. This procedure is performed at 15-18 weeks of pregnancy. The risk of pregnancy complications in amniocentesis is 0.2%.  Amniocentesis is made through the peritoneum under ultrasound control, in order not to damage the placenta. Vaginal amniocentesis is also possible, but this approach is rarely used. 8-10 ml of liquid is taken from the amniotic cavity. With biochemical parameters of fluid, only the concentration of alpha-fetoprotein (AFP) is diagnostically significant. The level of AFP increases significantly with anomalies of the neural tube and defects of the anterior abdominal wall

Cordocentesis – taking blood from the umbilical cord, is carried out under the control of ultrasound. The procedure is carried out in the period from 18 to 22 weeks of pregnancy. Blood samples undergo cytogenetic (lymphocytes are cultured), molecular genetic and biochemical studies.

At the present stage, there are already non-invasive (non-surgical), safe tests of genetic diagnosis of the fetus. Panorama test, which is based on digital quantitative analysis of fetal extracellular DNA, which circulates freely in the mother’s blood.

Panorama is the only non-invasive prenatal screening test that distinguishes mother extracellular DNA and fetal DNA through a single nucleotide polymorphism sequencing (SNP) method.

Reliably detected aneuplodia on chromosome 21 (Down syndrome), on 18 (Edwards disease), on 13 (Patau disease), X Turner syndrome, gonadal dysgenesis, Klayfelter’s syndrome. Triplody, microdeletion syndromes (Di Georgy, Angelman syndrome, feline scream, Prader-Willi) are also reliably detected. Accuracy of results -99%. The test can be carried out with 9 weeks of pregnancy. Optionally, you can determine the sex of the fetus.

In some Muslim countries, premarital karyotyping is widespread. This is a karyotype analysis (cytogenetic study). It identifies the chromosomal set of a person, the carrier of which gene mutations is a person and what is the future risk of having children with hereditary diseases in a married couple.

Also, karyotyping is recommended for couples with habitual miscarriage, having a child with developmental defects, stillbirth, the presence of hereditary diseases in relatives, men with severe spermatogenesis, women with primary or secondary amenorrhea, premature menopause, women with close relatives (mother, sister) suffered from breast cancer and ovarian cancer (BRCA-1 BRCA-2 gene mutations).