Pre-implantation genetic diagnosis (pgd) for heart disease determined by genetic factors

PGD is gradually becoming a practical tool in medical practice for inherited disorders and assisted reproductive technology [1]. In addition to PGD application to the conditions presented at birth, it appeared also attractive to avoid the birth of carriers of those disorders that may or may not manifest in later life, including common diseases with genetic predisposition, such as inherited forms of heart disease [2,3]. The first PGD for heart disease was performed for HoltOram syndrome (HOS) [2], characterized by atrial septal defect and cardiac conduction disorder, although the clinical manifestations may be extremely variable, not usually being presented at birth, or presented only with a sinus bradycardia, as the only clinical sign which might be left unnoticed. So it is a typical condition for which PGD if very attractive option, allowing to reproduce without fear of producing offspring at risk of developing HOS with risk for sudden death. The importance of PGD in this group of conditions is due to the fact that there is no current prospect of their treatment, as the disease may manifest despite pre-symptomatic diagnosis and follow up. So PGD seems to provide a possible relief for the at-risk couples to reproduce without much fear that their prospective children could be at high risk for premature or sudden death. This paper presents the world’s largest experience of PGD for inherited heart disease, performed for couples at risk who were able to avoid the risk and produce healthy children free of predisposition to inherited heart disease. The application of PGD has currently been extended to an increasing number of common disorders with genetic predisposition, including inherited heart disease, the prevention and treatment of which presents an important challenge. The major problem is that no pre-clinical diagnosis and preventive management exists, with high risk of premature or sudden death. We previously described the first series of 18 PGD cycles for 5 different inherited cardiac diseases, and showed feasibility and extremely high utility of preventing inheritance of genes predisposing to these conditions. The present paper summarizes the cumulative experience of 51 PGD cycles for 14 cardiac diseases, determined by 23 different gene mutations. This resulted in the embryo transfer in 44 of 51 PGD cycles, yielding 29 (66 %) unaffected pregnancies and birth of 27 healthy, disease predisposition free children. This is the world’s largest PGD experience, demonstrating important clinical implications of PGD for preventing inheritance of predisposing genes for heart disease, as practical means for avoiding the risk of mortality or premature or sudden death in offspring of couples carrying a heart disease predisposing genes.