Victor Chang Institute in the News

Media Release: New discovery on congenital birth defects

Nature and Nurture: World-first discovery sheds new light on birth defects

6 April 2012

Scientists in Sydney, Australia, have made a landmark discovery that could help women minimise or even avoid the risk of having a baby born with congenital birth defects. The study is published today in the prestigious international journal Cell.

The scientists from Sydney’s Victor Chang Cardiac Research Institute (VCCRI), show for the first time how ‘nature’ and ‘nurture’ interact to increase the severity and likelihood of developing birth defects, including abnormalities in the heart, kidneys, brain, limbs, and craniofacial regions (cleft palate).

They show how hypoxia, or a period of low oxygen during pregnancy, combined with a genetic risk factor of having only one functioning copy of a gene, dramatically increases the chances of a baby being born with congenital scoliosis, a malformation of the spine that affects around 1 in 1000.

Professor Sally Dunwoodie, Head of the Embryology Laboratory at the VCCRI, Professor at the University of NSW and senior author on the study, says the findings take us a step closer to understanding why some people in families develop diseases and others don’t, and importantly, simple strategies that mothers could adopt to help prevent such defects occurring.

“We’ve long suspected that it is genes or our environment that cause birth defects, but up until now, the majority of these have been largely unknown. This is the first time anyone in the world has shown that both ‘nature’ and ‘nurture’, in combination, are molecularly responsible for causing many birth defects.

“This research is hugely exciting and will help us to genetically diagnose a whole range of birth defects, and give advice to women on how and when to avoid certain activities when pregnant. We hope it will eventually lead to the development of therapeutics to stop these defects occurring in the first place.”

Hypoxia during pregnancy can be caused by a range of circumstances including poorly controlled sugar levels in diabetics, smoking, high altitude, prescription and recreational drug-use, anemia or a poorly functioning placenta.

Professor Dunwoodie and her colleagues studied individuals with congenital scoliosis and found that having just one, instead of two functioning copies of a known gene[1] from either mum or dad, was a major risk factor for causing the abnormal formation of vertebrae in embryonic development.

They then went on to test the genetic risk factor in a mouse model combined with an environmental ‘insult’ in the form of hypoxia. Surprisingly, they found a marked increase in spinal abnormalities in the offspring, when the mothers were exposed to only 8 hours of low oxygen during an entire 21-day pregnancy.

“We found that the combination of the genetic risk as well as exposure to low oxygen, resulted in our subjects being up to 10 times more likely to develop congenital scoliosis, than those that only had the genetic risk factor,” continued Professor Dunwoodie.

“What this brief period of low oxygen essentially did was disrupt the pathway responsible for the development of the spine, and we know that the same pathway is used in the development of limbs and many organs, including the heart, kidneys, brain and craniofacial region,” added Professor Dunwoodie.

Sally and a student

Professor Bob Graham, Executive Director of the VCCRI, says around 25 percent[2] of patients with congenital scoliosis also have some form of congenital heart defect, indicating that a single environmental ‘insult’ such as hypoxia, can potentially affect the development of more than one organ in the body.

“This study provides a new paradigm for the interaction between our genes and environment, and may account for a lot of diseases that we haven’t understood before, such as many different forms of congenital heart disease, and conditions like cleft palate.

“It may not necessarily be a lack of oxygen that allows the underlying gene defect to be revealed, it could be a lot of other environmental factors, such as anemia or lack of folate. But the message is, if you have a family history of disease or you know you have a defective gene, mums need to be extra careful during pregnancy,” added Professor Graham.

The team of researchers has begun working on similar studies in congenital heart defects, which affect around 1 in every 100 babies born in Australia every year.[3]


[1] The genes that were sequenced were the MESP2 and HES7 genes. Here loss of a single functional copy caused congenital scoliosis, where loss of both copies causes the more severe vertebral disorder called spondylocostal dysostosis (Whittock et al., American Journal of Human Genetics, 2004; 74(6), 1249–1254; Sparrow et al., Human Molecular Genetics, 2008; 17(23), 3761–3766).

[2] Congenital heart disease is observed in up to 25% of patients with congenital scoliosis. (Basu et al: Spine 2002; 27(20):2255–2259).

[3] This study was funded by the Australian National Health and Medical Research Council (NHMRC)

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The Victor Chang Cardiac Research Institute acknowledges Traditional Owners of Country throughout Australia and recognises the continuing connection to lands, waters and communities. We pay our respect to Aboriginal and Torres Strait Islander cultures; and to Elders past and present.

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