Clinical Guideline for Preimplantation Genetic
Testing in Inherited Cardiac Diseases
Carrying a genetic mutation can raise questions and concerns for patients at the moment they decide to have children: what are the chances that my child inherits the mutation and will also develop the disease? Preimplantation genetic testing (PGT) is a combination of in-vitro fertilization (IVF) with embryo selection, which means that sperm and egg are brought together outside the body in a laboratory and the fertilized egg is placed in the woman’s uterus, but in the end only embryos without the genetic mutation will be placed back for a pregnancy. However, PGT is a long and intense procedures, and the benefit should outweigh the risks, especially since the risk of developing the disease differs per mutation carrier. In the Netherlands, a multidisciplinary team (MT) assesses all individual cases to estimate the risk reduction and decides whether PGT should be approved. In this study we developed a decision model that can help to estimate the risk reduction when PGT is performed to remove the mutation and make sure that the child will not be carrier of the familial disease-causing gene variant.
Over the past decades, 83 couples were referred for PGT for an inherited cardiac disease in the Netherlands (19 different genes for 8 different inherited cardiac diseases (cardiomyopathies and arrhythmias). We developed a decision model based on published risk prediction models and literature to estimate the severity of the cardiac disease and the risk of disease development for a future child if it would carry the familial mutation. Afterwards, we applied this model retrospectively on all 83 couples to test whether the model could estimate the risk reduction, and if the decision of the model was in line with the decision of the MT. This was the case for 95% of the cases. Then the model was prospectively tested in 11 new referrals, where it showed to be a valuable and objective tool that can easily and rapid provide information to doctors and patients whether the risk reduction by PGT outweighs the burden of the trajectory.
Conclusion: the number of PGT referrals for inherited cardiac diseases is increasing rapidly. This decision model can help in decision-making whether PGT is a good option for a couple with an inherited cardiac disease.
Verdonschot JAJ, Hellebrekers DMEI, van Empel VPM, Heijligers M, de Munnik S, Coonen E, Dreesen JCMF, van den Wijngaard A, Brunner HG, Zamani Esteki M, Heymans SRB, deDie-Smulders CEM, Paulussen ADC. Clinical Guideline for Preimplantation Genetic Testing in Inherited Cardiac Diseases. Circ Genom Precis Med. 2024 Mar22:e004416.doi: 10.1161/CIRCGEN.123.004416. Epubaheadofprint.PMID:38516780.
Prepared by Job Verdonschot and Ruth Biller