Genetic Counseling

The enormous technological advances and scientific acquisitions of the last decades have given a significant increase in the knowledge of the biological basis of many hereditary diseases.

In particular, the studies carried out on the basic mechanisms of many genetic diseases have made it possible to identify the molecular causes of numerous genetic diseases. These acquisitions have made it possible to develop genetic tests capable of identifying the genetic defect even in the prenatal period. Unfortunately, there are still many genetic diseases whose molecular defect is not known, although the mode of transmission and the clinical consequences are known.

There are also complex genetic diseases whose origin is determined by mutations in different genes as well as the interaction with environmental factors that contribute in different ways to the development of the disease.

Genetic counseling is an integral and essential part of a genetic test and is necessary to define the diagnostic possibilities and the relative reliability.

During the consultation, information is collected which, through the personal and family medical history, makes it possible to establish any risks related to specific genetic diseases.

In particular, the execution of genetic tests requires that those who undergo them have a vision and

approve an informed consent explaining the risks, limitations and consequences of such examinations.

The communication of the results obtained, both for postnatal and prenatal genetic tests, is the moment in which the geneticist communicates the information obtained and the possible consequences to the proband or his family members. Counseling should not be directive but provide all possible information for understanding the problem identified, especially in prenatal diagnosis.

Prenatal genetic counseling consists of an interview that a couple at risk of genetic disease (chromosomal or molecular) carries out with the geneticist. The interview is used to identify any risks for specific genetic pathologies and evaluate the diagnostic possibilities of any tests required for prenatal examinations.

In summary, genetic counseling allows, in most cases, to answer the following questions:

• Is the disease I suffer from hereditary?
• Is the disease that afflicts my family member hereditary?
• Can I develop it too?
• Can I pass it on to my children?
• Is there a test that allows me to know if I have passed on the disease I suffer from to my child and even before birth?
• Are there any therapies to cure the identified genetic disease?

Prenatal diagnosis is a set of instrumental and laboratory investigations aimed at monitoring the state of health of the baby during the entire duration of pregnancy so as to allow the identification of defined pathologies of different origins (hereditary, infectious, environmental, etc.)

The methods used for prenatal diagnosis can be roughly divided into:

NON-INVASIVE METHODS (ultrasound, biochemical investigations, combined tests)

INVASIVE METHODS (CVS, amniocentesis, cordocentesis, fetoscopy)

At present, the generally accepted guiding criteria for access to prenatal diagnosis are as follows:

• Advanced maternal age. The definition of advanced age varies according to the centers where the examination is carried out, but generally it is at least 35 years old. The selection of this age is due to the fact that at 35 the risk of having a fetus with an abnormality is approximately equal to the risk of abortion related to the invasive procedure. This risk differs depending on the procedure used.

Villocentesis 1-2%

Amniocentesis 0.5-1%

Cordocentesis 2-4%

It should be borne in mind that these percentages are probably overestimated, as fluctuations, even sensitive ones, are closely related to the skill, experience and instrumentation of the operator. In general, the principle is that the more tests are performed, the lower the risk of miscarriage following the invasive procedure.

• Previous pregnancy with de novo chromosomal abnormality. For example, a 30-year-old woman with a previous child with Down syndrome has a recurrence risk of 1/100 against 1/390 relative to age in the general population. According to some authors, this increase in risk is partly explained by a low cryptic parental mosaicism but in most cases the mechanism that explains this increased risk is not known.
• The presence of structural anomaly in one of the parents. In this case, the risk must be assessed based on the type of inherited anomaly and, sometimes, depending on the parental origin.
• The presence of a family history for a diagnosable disease by biochemical or genetic analysis. These are generally anomalies in single genes that have a 25 or 50 percent risk of recurrence (Cystic Fibrosis, Myotonic Dystrophy, Neurofibromatosis, Alpha and Beta Thalassemia, Sickle Cell Anemia and many more)
• X-linked disease for which there is no specific test. When an alternative method is not available, the parents of a boy suffering from a disease associated with the X chromosome can use sex determination to decide whether or not to terminate a pregnancy given the high risk of recurrence.
• Risk of neural tube defects. First-degree relatives of patients with neural tube defects are eligible for amniocentesis.
• Maternal serum and ultrasound screening. Genetic tests and further investigations are recommended in women in whom the risk of genetic abnormalities is highlighted in pregnancy on the basis of positive screening tests (Bi-test, Tri-test or other combined tests). Ultrasound evidence attributable to certain genetic diseases may be sufficient indications for performing an invasive procedure.

These are the most common indications for accessing invasive prenatal diagnosis. Particular situations such as pregnancies following medically assisted fertilization, the presence of particular ultrasound pathologies that require particular genetic techniques, particular emotional state of the pregnant woman must be carefully evaluated during genetic counseling. Genetic counseling is always the first step to take before deciding on the use of invasive procedures for genetic, molecular or biochemical analyzes in prenatal diagnosis.