Rare congenital disorders, imprinted genes, and assisted reproductive technology

Abstract

Context: During the past two decades, assisted reproductive technologies (ARTs) have revolutionised the treatment of infertility. ARTs now account for between 1% and 3% of annual births in many western countries and in-vitro fertilisation (IVF) services are growing worldwide. In general, the incidence of abnormalities at birth is reassuringly low and children develop normally. Nevertheless, it is important to monitor the safety of ARTs as clinical protocols evolve and new technologies emerge.

Starting point: Three recent studies all report an unexpectedly high incidence of Beckwith-Wiedemann syndrome (BWS) in children conceived with ARTs. Six of 149 cases were reported from a British BWS registry (J Med Genet 2003; 40: 62-64); the same numbers were recorded in a French registry (Am J Hum Genet 2003; 72: 1338-41), and a further seven children have been reported in the USA (Am J Hum Genet 2003; 72: 156-60). These frequencies are extraordinarily high for such a rare congenital condition and such findings are reminiscent of reports of sporadic cases of the imprinting disorder, Angelman syndrome, which has also been linked with ARTs. WHERE NEXT? Continuing surveillance of children conceived with ARTs is needed, including monitoring birth defects, development, and cancer. Studies will need to be prospective and multicentre, and should include molecular characterisation of epigenetic abnormalities, including the methylation status of imprinting control regions within imprinted gene clusters.