BioNews reporting from ESHRE conference, Copenhagen: Beckwith-Wiedermann syndrome (BWS) is the only rare genetic 'imprinting' disorder linked to the use of assisted reproduction techniques (ARTs), according to the results of the largest study carried out to date. Researchers at University College in London investigated a possible link between ARTs and four different imprinting disorders, and found that BWS was the only condition that showed a significantly increased risk. The team presented their results at the annual meeting of the European Society of Human Reproduction and Embryology (EHSHRE) in Copenhagen.
Genetic imprinting is the process by which certain mammalian genes are switched off during early embryo development, according to whether they were inherited from the father or mother. BWS is one of several imprinting disorders, which are all caused by disruptions to imprinted genes or to the imprinting process itself. In people without BWS, only the paternal copy of a gene called IGF2 is switched on, but in people with the condition, both the maternal and paternal copies are active. IGF2 makes a growth factor protein, and the symptoms of the disease include an enlarged tongue, liver, spleen, kidneys and pancreas and an increased risk of certain tumours.
American researchers at Johns Hopkins University and the University of Washington first identified a possible link between IVF treatment and BWS in 2003. They found a prevalence of BWS in IVF children of one in 2500, compared with a prevalence of between one in 15,000-35,000 for naturally conceived babies. Two other groups of researchers later confirmed a link between ARTs and an increased risk of BWS, in studies of UK and Australian BWS patients. Other studies have suggested a link between ARTs and other rare genetic conditions
In the latest study, the scientists looked at BWS and three other imprinting disorders - Angelman syndrome (AS), Prader-Willi syndrome (PWS) and Transient Neonatal Diabetes (TND). They contacted UK support groups for the conditions, and asked parents of patients whether they had used ARTs to conceive their affected children. Out of 82 replies from families with a BWS child, 10 were conceived using ARTs (12 per cent). However, the researchers found no such link in the children affected by AS, PWS or TND. The team also found that all the ART-conceived affected BWS children showed disrupted DNA 'methylation' - the chemical process by which imprinted genes are modified and switched off.
Team leader Alastair Sutcliffe says the findings are encouraging. 'Not only have we found a possible mechanism for the occurrence of BWS, but we found no significantly higher rate of any disorder in children born after ART apart from BWS', he said. The study also showed that no particular method of ART was linked to an increased risk of BWS. 'The problem could be in the [embryo] culture media, or it could simply be that the parents are naturally infertile because of a genetic abnormality', said Sutcliffe.
The researchers now plan to carry out further research on retinoblastoma, an inherited childhood eye cancer also thought to involve imprinting. Sutcliffe said this work would be helped 'enormously' if the UK's Human Fertilisation and Embryology Authority and the cancer registries were to link their databases. Although disorders such as BWS and retinoblastoma are unusual, this is 'irrelevant' to a parent with an affected child, said Sutcliffe. 'They simply have a sick child and it is just as important for us to try and find treatments and cures for these conditions as for those that are more common', he pointed out.