New research suggests that infants born using assisted reproduction face a higher risk of certain genetic disorders.1 But the good news, say the researchers, is that they found a higher risk of contracting only one of these disorders—Beckwith-Weidemann syndrome (BWS)—of several abnormalities studied.
The other genetic disorders included in the study were Transient Neonatal Diabetes (TND), Angelman syndrome (AS) and Prader-Willi Syndrome (PWS). "It has been known for some time that BWS, for example, was associated with ART," said the study's head researcher, Alastair Sutcliffe, MD, in the Department of Child Health at University College in London, "and we set out to look at the association of all four disorders and assisted conception."
The study's findings were released at the 21st Annual Meeting of the European Society of Human Reproduction and Embryology, being held this week in Copenhagen, Denmark.
Unusual Syndrome
Beckman-Weidemann syndrome is a rare disorder that occurs in approximately 1 in 15,000 births. The most common characteristics include large tongue, abnormally large body size, abdominal wall defects, above-average birth weight, uneven growth of limbs or organs, low blood sugar, difficulty swallowing or eating, hearing loss, speech defects, and occasional behavior abnormalities. Children with the disorder face about a 10% increased risk of developing kidney or liver cancer.2
The disorder originates from certain abnormalities in genes, and children can acquire it from one or both parents.
Assessing Risks in ART
For their research, Sutcliffe and his colleagues contacted patients throughout the UK who were members of a support group focusing on the disorders. The researchers obtained family histories and information about whether they had conceived any children through assisted reproduction, and if so, the types of assisted reproductive therapy (ART) they had used.
Of 82 replies from the parents of children with Beckwith-Weidemann syndrome, 10 had previously used ART to conceive. After evaluating the risk of contracting any of the four disorders linked to the use of assisted reproduction, Sutcliffe's group found it was limited.
"We found that BWS was the only disorder where there was a significant risk for children conceived by ART," Sutcliffe said. Whereas those children with the other disorders were carrying a mix of gene abnormalities, the researchers found that those with BWS may have contracted the disorder through a specific genetic mechanism: loss of methylation (meh-thuh-LAY-shun) acquired from the mother. Methylation is a mechanism used to inactivate parts of a chromosome to prevent a disorder from occurring.
Limited Risk Found
Sutcliffe says his findings should be 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. "Neither did we find that any particular method of ART was implicated."
While the reasons behind the higher risk of BWS weren't analyzed in this research, Sutcliffe says it could have something to do with the way embryos are stored prior to their transfer to the uterus in IVF procedures, or it could relate to possible genetic abnormalities of the parents, which caused their infertility in the first place.
One of the first studies to suggest a possible link between ART and Beckwith-Weidemann syndrome was published in early 2003.3 Seven of 65 children in the study had been diagnosed with the birth defect, and were conceived using ART, doctors at Washington University in St. Louis had found. That translates to a risk of between 7% and 8%.
"We are now planning to do a further study on the childhood eye cancer, retinoblastoma, where it is believed that imprinting is involved," he said. Imprinting defines a change in the activity of a certain gene depending on whether it was acquired from the mother or father. This includes gene disorders, as well. If the disorder is inherited from the mother, a certain syndrome might occur, whereas if it is inherited from the father, an entirely different syndrome may result.
Although these genetic disorders are fairly rare, that's irrelevant to the parents of a child who's been diagnosed with such a condition, Sutcliffe pointed out. "They simply have a sick child, and it is just as important for us to try and finding treatments and cures for these conditions, as for those that are more common."
1. European Society of Human Reproduction and Embryology 21st Annual Meeting. 2005 Jun 19-22. Copenhagen, Denmark.
2. National Cancer Institute. Questions and Answers About Living with Beckman-Weidemann Syndrome. Available at: http://cis.nci.nih.gov/fact/3_67.htm. Accessed June 21, 2005.
3. DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith-Weidemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet 2003 Jan;72(1):156-60. Epub 2002 Nov 18.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
