Dr. Francesca Girolami, Cardiogenetics - Meyer Pediatric Hospital
If a parent has cardiomyopathy, should the minor child be subjected to genetic testing? On this delicate and complex subject there are specific guidelines at American and European level. Francesca Girolami, geneticist, who works at the Meyer pediatric hospital in Florence, tells us about it, where there is a Cardiogenetics laboratory belonging to the Pediatric Cardiology facility consisting of a team of two geneticists and seven cardiologists.
Dr. Francesca Girolami
Francesca Girolami, geneticist, you work in Cardiology at the Meyer pediatric hospital in Florence, if a parent is affected by cardiomyopathy and the responsible genetic defect has been identified, is it advisable to also have the children undergo a genetic investigation?
This is a very sensitive issue, it must be evaluated case by case with extreme caution. If the children do not show signs of cardiomyopathy and are minors, the investigation is postponed until they are at least 10/12 years old, if not at the age of majority, in accordance with specific international guidelines (European and American). The reason for this indication lies in the fact that, even knowing the presence of the genetic defect early, at the moment there are no concrete possibilities of therapies or preventive treatments that allow the eventual manifestation of the disease in the following years. Therefore, a possible positive response from the genetic test in a child who does not show signs of heart disease (and who may never develop it, or much later in age) becomes a 'label' that can affect his and his parents' life. also from a psychological point of view. The age of 10/12 years that the international guidelines indicate as the first "appointment" to evaluate the execution of the genetic test is also motivated by the fact that this is the moment in which children often take up a sport. We know that, for some forms of cardiomyopathy, the presence of the genetic defect can lead to the interruption of competitive sports for preventive purposes. The message we want to convey to families is this: in general up to 10/12 years it is not advisable to consider genetic analysis on unaffected minors, except in very special cases.
How is genetic testing done in the child?
The genetic test is performed together with genetic counseling, an interview through which the child's parents are informed on how to perform the test (which is performed on a small blood sample), on the possible results, advantages and limitations. At the end of the interview, the informed consent to perform the test will be signed. Often the path includes more than one meeting by the team of professionals (cardiologist, medical geneticist, laboratory geneticist) in order to address the various aspects and also give the necessary time to reflect on the information given.
Sometimes, the psychologist also intervenes. It is very important to know how to listen to and take into consideration the opinion of the minor, especially if it is a question of adolescents
What are the cases in which the genetic investigation of a minor is strongly indicated?
When cardiomyopathy is suspected in the minor, there is an indication to perform the genetic test to help the cardiologist in the diagnosis and possible treatment. It is thus possible to distinguish whether we are dealing with a form attributable to one gene or another, with important repercussions on the cure. For example, genetic testing can identify mutations associated with syndromic or metabolic pictures (sometimes associated with mental retardation, alterations in the face or problems of the peripheral muscles) with a different prognosis than the classic forms and requiring targeted therapies. Once the mutation has been identified, the cascade test can be performed on the whole family. It is also possible to calculate the recurrence risk for future pregnancies and in some cases offer the possibility of an antenatal diagnosis.
Is identifying the gene involved therefore essential to differentiate the cure?
Today, therapies are being developed that are increasingly based on knowledge of the patient's altered gene. For most of the Cardiomyopathies, even if they are still experimental studies, the prospect is to obtain personalized therapies and it is not utopian to think that over the next ten years the treatments can be set on the basis of the genetic "imprint" of each. Genetics is therefore opening up horizons that were unthinkable until recently. In the last decade, genetics has undergone a significant revolution thanks to new genome sequencing methods, called Next-Generation Sequencing (NGS), which allow to study numerous genes simultaneously in many patients at low cost. It is a massive sequencing that allows the analysis of even 100/150 genes up to the entire genome.
Give us a concrete example
Doing a genetic analysis is like reading a book with many chapters and looking for the wrong word among many, the one that fails to make sense of a sentence. Similarly, new technologies make it possible to find the mutation, the one out of tune, within a huge number of variants quickly and in previously unexplored regions of the genome.
Is it always possible to detect the mutation?
No, the genetic test can also give a negative result. This means that, based on current knowledge and technology, we have not been able to detect the mutation. However, we cannot exclude that this exists and that we could identify it in the future as a result of new knowledge. On the other hand, when the result is positive, it means that the variant has been identified and that this will help the clinician in the diagnosis and treatment. Furthermore, in this case the variant can also be searched for in other family members. There is also a third result, which we define as "inconclusive": that is, we have been able to identify one or more variants, but we are unable to say whether or not they are related to the disease. This is a result that immediately offers no clinical advantage for the patient, but which must be re-evaluated by the geneticist over time on the basis of new studies and research. The technological potential has gone far beyond our knowledge of the human genome. Today, based on current knowledge, we are able to identify the mutation in about 50% of cases with cardiomyopathies. Genetics is not as omnipotent as is sometimes believed.