In recent years, prenatal diagnosis has become more complete and is now also used in the search for various genetic pathologies.
In fact, in the 1980s, amniocentesis and chorionic villus sampling only studied the karyotype, while, today, the introduction of ever more modern and accurate genetic methods has made it possible to discover a large number of pathologies before birth which, compared to a chromonsal prognosis, is often more serious.
It is common knowledge today that there are various levels of investigation on amniotic fluid and chorionic . There are basically two types of test. The first is a routine investigation based on the decision of the couple who would like information on the state of health of health of their child. The second procedure regards testing which aims to study a specific problem and generally involves “high risk” couples. In these cases, genetic diagnosis explores precisely the pathology that is considered to be of the highest risk in the couple or because a sonography has indicated that further research is necessary to obtain a more complete picture.
The most interesting characteristic of prenatal diagnosis is linked to the desire of the parents to receive information regarding the greater number of pathologies and with a higher level of certainty. In consideration of the above, it is possible to offer the couple 4 diagnostic panels. These are also given to low and medium risk couples in order to satisfy their desire to receive as much information as possible.
The following histogramme provides an immediate view of the diagnostic potential of the 4 panels which can be carried out on the amniotic fluid or the chorionic villi.
Let’s make an examination in chronologoical order of the 5 panels in clinical practice:
-Traditional amniocentesis/CVS was the first to be introduced, in the early 1970s. Traditional amniocentesis/CVS can only diagnose numerical pathologies of the chromosomes (aneuploidy) and the biggest alterations in chromosonal structure. The graph illustrates the percentage of pathologies diagnosed per 100 subjects that are carriers of genetic disorders. This figure is less than 5% .
- Amniocentesis/CVS with the partial study of DNA, expands the range of traditional amniocentesis/CVS through the use of various genomic sequence methods (e.g. MLPA or PCR etc.). and can identify the most frequent genetic disorders (cystic fibrosis , spinal muscular atrophy (SMA), fragile X syndrome, hereditary congenital deafness, Duchenne muscular dystrophy). This group of genetic disorders adds an extra 2% to the number of subjects diagnosed. Therefore, the figure passes form from approximately 5% of diagnoses obtained with the first technique to about 7 % with the additional tests.
- Recently introduced molecular amniocentesis/CVS, (around the year 2005), searches for microdeletions and microduplications through COMPARATIVE GENOMIC HYBRIDITATION techniques (aCGH). This research, which some people also call “molecular karyotype” due to its ability also to diagnose many aneuploidies, cannot be separated from traditional cytogenetics , due to the possible failure to diagnose various chromosomal defects. With this technique , we can add another 1% of diagnosed subjects to the molecolare karyotype, the percentage, therefore, passing from 5% to approximately 6%.
- Molecular amniocentesi/CVS with the partial study of DNA is a combination of all the above-mentioned techniques. Many laboratories, offer a more complete diagnosis that includes additional information from both the second and the third diagnostic panel. Therefore, to the 5% of the karyotype, it adds the 2% of the most frequent genetic disorders and the l’1 % of the microduplications and microdeletions. Although this panel, until recently, represented the most complete form of prenatal diagnosis, in reality, its diagnostic potential is less than 5% superior to traditional prenatal diagnostics. The figure, in fact, only increases to about 8%.
- The real diagnostic revolution regarded the introduction of the 4th panel based on the study of the exome which has made it possible theoretically to include the complete list of known genetic pathologies. This panel is known as the genomic amniocentesis/CVS or NGPD for short. It adds a study of the exome which includes in the diagnostic panel all that can be legally and ethically investigated. These types of research can diagnose between 70 and 80% of all genetic disorders. It cannot arrive at a figure of 100% because it excludes all the extremely rare pathologies which are of unknown or dubious genetic origin or those for which investigations are “unethical “. In fact, NGPD does not study single-nucleotide polymorphisms (SNPs), i.e. those gene variations that make people susceptible to a large number of diseases, which range from genetic disorders to cancer. In the same way, NGPD does not take into consideration late onset diseases such as Alzheimer or those that involve the psychiatric characteristics of the subject.