Challenges of the genetic counselling

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2021-1-HU01-KA220-HED-000027613 - COHRICE
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SYLLABUS

Challenges of the genetic counselling

(Basic level)

The importance of genetic counselling is based upon the fact that 0.65% of all deliveries result a newborn with a major chromosomal abnormality, and in 2-3% of pregnancies major congenital anomaly is detected. The incidence of monogenic inherited disorders is 3.6/1000 deliveries, and chromosomal abnormalities are responsible for up to 30% of all perinatal loss. 

What is genetic counselling?

Genetic counselling is a communication procedure between the parents and specialist, in order to reveal the chances of a potential congenital anomaly to develop, or to manifest. During this process the specialist helps to explain the different diseases to the parents, including the diagnosis, the symptoms, the main characteristics, and the way of inheritance. The first genetic counselling was started in the 1940’s, separated from eugenics. A conversation should always focus on the followings: provide information about the status, treatment options, risk assessment, methods of genetic diagnostics, limitations and risk of the diagnostic interventions, alternative options, practical advice, and the risk of the following pregnancies. The counselling requires a specialist with superior communication skills, and it is also crucial to discuss the certain conditions with the parents through a way they all understand it, respecting their social, religious, and ethnical status.

Which invasive methods can be used in prenatal diagnostics?

Through invasive prenatal genetic diagnostic methods, we collect from the uterine cavity. These procedure involve a certain level of risk, therefore it should only be carried out when strict indications apply: maternal age ≥ 37 by the time of fertilization, nuchal translucency (NT) was found to be ≥ 3mm during the first trimester scan, maternal serum biomarker assessment resulted high risk (1:250), abnormal ultrasound finding during the second trimester ultrasound scan, one of the parent is balanced translocation carrier, positive family history for chromosomal abnormality in the previous pregnancy(es). Invasive procedures include genetic amniocentesis (GAC), chorionic villous sampling (CVS), percutaneous umbilical blood sampling (PUBS). See these procedures discussed in detail in the presentation.

What kind of non-invasive screening examinations are available nowadays?

Screening methods are designed to evaluate high genetic risk pregnancies from otherwise unproblematic, or low-risk pregnancies. The requirements of the screening methods are the followings: it should be designed to diagnose a certain condition; it should be reliable and safe; it should have low a false negative-false positive ratio; high risk cases should be further investigated till diagnosis is achieved; there should be an ethical agreement between the doctors and the society according to the screening procedure.

Which biomarkers can be used for screening?

Historically alpha-foetoprotein (AFP) (a protein produced by the fetal liver, which appears in the amniotic fluid, and able to bypass the placenta) determination from maternal serum was the first available method in 1972. The clinical implementation of AFP was limited to existence of fetal neural-tube defects (high), chromosomal abnormalities (low), twin pregnancies (high) and intra uterine demise (low), in an era when the ultrasound was not widely available. AFP levels were determined at gestational week 16. Since studies concluded that AFP alone is not reliable tool to evaluate high risk patients, they started to add other markers such as free serum human chorionic gonadotropin (hCG) and pregnancy associated plasma protein-A (PAPP-A). These markers were found to demonstrate correlation with the presence of trisomy 21 (Down syndrome), hCG increase, PAPP-A decrease was found in those cases. During the second trimester beside AFP unconjugated maternal serum Oestriol (ET) and inhibin-A levels showed correlation with fetal chromosomal abnormalities.  Serum biomarker level assessment are found to be very useful tools for young mothers (under age 37), because in this population 90% of all Down syndrome fetuses could be prenatally diagnosed, although between age 37-40 population it is useful augmenting tool beside the invasive method in the decision making. Although over the age 40 risk of chromosomal abnormality exceeds the abortion risk of the invasive methods, therefore it is the recommended method. 

What is NIPT?

The non-invasive prenatal testing (NIPT) is a method based on the detection of the fetal DNA from the maternal serum. It was first described in 1997, by Lo et al. The fetal DNA originate from the chorion and build up 20% of free circulating DNA in the maternal serum. The method requires at least 5% of free fetal DNA in the maternal serum, and it has high detection rate (99.4%), with <1% false positive and false negative rate, which makes the method into a breakthrough in reliability and detection of chromosomal abnormalities. Till date it is not covered by the social security system of all EU member states, therefore the patients need to pay for it, but upon payment it available for the general pregnant population.

Conclusion

For the prenatal diagnosis and screening of trisomy 21 includes invasive and non-invasive methods are also available and effective. Invasive methods are recommended if certain strict criteria are met. In general, we can conclude if the risk arise from the intervention exceeds the risk of the occurrence of a congenital anomaly, the invasive method is recommended. NIPT opened new perspectives and shifted the focus of prenatal testing into the first trimester of pregnancy. In an aging European society, the age-related increased risk of chromosomal anomalies is serious problem. The main goal of genetic counselling to allow parents to have access to the most modern techniques, in order to achieve a healthy child.

Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Foundation for the Development of the Education System. Neither the European Union nor entity providing the grant can be held responsible for them.