Genetic counselling: When and Why?

Genetic testing is a powerful tool that was once confined to research settings, but it is now routinely used for diagnostic, prognostic, and therapeutic purposes. The spread of genetic testing gave a unique opportunity to understand the pathophysiology of inherited heart diseases but brings with it challenges and responsibilities regarding the use of this information for patients and their families.[1]
Thus, along with genetic testing, the concept of genetic counselling (GC) has evolved. GC is “the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease”. [2] It is an integral part of the management of all patients with inherited heart diseases and their family members, and specialized centres increasingly have genetic counsellors and/or clinical geneticists as a part of their team. Genetic counselling is a process starting with a specialized consultation for a patient with a potential inheritable disease, discussing with him/her and their relatives about the potential impact of the result (in terms of diagnosis and risk stratification), about the modality of transmission, and the way to anticipate, prevent or modulate the risk (Peter Harper; Practical Genetic counselling).
Based on this definition, the Genetic Counsellor foresees a pre-test phase that includes a discussion before the decision to undertake genetic testing and a post-test consultation at/after the return of the results.

During pre-test GC the genetic counsellor:

• Collects a detailed family history creating a 3- to 4-generation family pedigree to evaluate the mode of inheritance.
• Communicates the specific type of test that will be performed including the genes investigated and by which technologies.[3]
• Explains the possible test results including the meaning of pathogenic/likely pathogenic variants (P/LP), variants of uncertain significance, and benign/likely benign variants.
• Communicates the potential implications for clinical care. The individuation of a genetic variant may have diagnostic value, for example discriminating phenocopies in hypertrophic cardiomyopathy phenotype, such as Danon disease, Pompe disease, PRKG2 cardiomyopathy, cardiac amyloidosis and Fabry disease. Furthermore, specific genotypes may be candidates for targeted therapies, such as enzyme replacement therapy for Pompe disease and Fabry disease, and transthyretin stabilizers or silencers in cardiac amyloidosis. A new frontier of genotype-targeted therapy is represented by gene therapy, which aims to intervene at the roots of the genetic disease by replacing a defective gene (gene replacement) or silencing the expression of a gain of function variant (gene editing).  
• Communicates the lifestyle implications, for example in arrhythmogenic cardiomyopathy, the presence of a P/LP variant even without a clinical phenotype, avoidance of high-intensity exercise including competitive sport may be considered (Class of recommendation level of evidence IIb,C).[4]
• Communicates the benefit of extending genetic testing to family members if a P/LP variant is recognized.
• Begins the discussion about the potential psycho-social consequences of a genetic diagnosis, for the patient and their family.

During post-test GC, the genetic counsellor:

• Provides the patient with the test results, giving potential explanation for the clinical manifestations of the disease, its natural history and specific implications for clinical care. Also reviews the meaning of a negative/uninformative result or VUS.
• Reviews the specific implications for the family
• Provides information about reproductive options if needed/appropriate.
• Provide contacts of patient organizations/associations
• Reviews in more detail, the psycho-socio-familial impact of the result

During every step of genetic counselling, the counsellor should provide psychological support.  Patients may be worried about the stigma associated with a diagnosis of genetic disease, may experience fear of sudden cardiac death, fear of inheritance risk to other relatives, and guilt about transmitting the disease to their children. A special case is represented by relatives who experience the sudden cardiac death of a young relative, who have a significant risk of poor psychological functioning, including post-traumatic stress and prolonged grief. While many patients and family members will benefit from psychosocial counselling, for some, treatment by a trained professional such as a clinical psychologist is required.[4]
Specific issues should be considered when counselling children and their families, including the competence of the child to decide on testing, the appropriate understanding of the child, and the incomplete and age-related penetrance of certain conditions. The guiding principle remains that any clinical or genetic testing should be in the child's best interests and have an impact on management or lifestyle. [4]
The counsellor should consider the “right not to know”, which consists in the decisional autonomy of the patients of controlling whether to receive genetic information and the possible desire not to know the possible result.  
In genetic testing the result could be uncertain, such as in the case of variants of uncertain significance, in which the available data are not sufficient to define the variant as pathogenic or benign. Dealing with the uncertainty of the result could be a source of concern, and it’s the counsellor's duty to be reassuring but at the same time underline the importance of clinical follow-up.
Genomic data interpretation is becoming always more complex and the interpretation of novel variants, the pathogenicity assessment and the clinical correlation require an interdisciplinary expertise in molecular and functional genomics and a deep clinical knowledge of the possible phenotypes, that can be found in dedicated expert centres. 
GC is an integral part of genetic testing with proven efficacy in improving knowledge, increasing satisfaction with decision-making, and reducing anxiety in patients and their families. [4]