[Preimplantation genetic diagnosis (PGD) for cancer predisposition syndromes]

Most cases of cancer are sporadic and only 5%-10% are inherited with variable penetrance. Whenever the causative mutation is known, prevention of affected offspring birth may be achieved by prenatal or preimplantation genetic diagnosis (PGD).

To devise a scoring system (SS) that appraises the justification of PGD for each patient and to evaluate the efficacy, reliability and accuracy of PGD for cancer predisposition syndromes in 48 cycles.

A semi-quantitative SS was developed by evaluating disease characteristics (onset, severity, inheritance pattern and penetrance) and patient clinical variables (infertility, objection to abortion and a need for diagnosis of additional genetic syndrome). PGD cycles were performed by blastomere biopsy of cleavage stage embryos, followed by single cell multiplex nested PCR for the cancer predisposition mutation and flanking polymorphic markers.

Seventeen couples referred to PGD for cancer predisposition. According to the devised SS, fourteen were accepted and 3 were declined. Of the 14 accepted couples, 13 had at Least one affected member and 11 couples required IVF anyway. A total of 48 PGD cycles were performed resulting in 8 pregnancies.

PGD for cancer predisposition genes is a possible and reliable procedure, suitable especiaLly for infertile carrier couples.

The assessment of the characteristics of the cancer syndrome and consideration of the variables of each couple enable, the justified application of PGD procedure. The continuous discovery of cancer predisposition mutations will result in an ever-increasing demand for PGD to prevent the transmission of Lethal mutations to the next generations.